Oligosaccharide glycosides having mammalian immunosuppresive and tolerogenic properties

Disclosed are novel oligosaccharide glycosides having mammalian immunosuppressive and tolerogenic properties, pharmaceutical compositions containing such oligosaccharide glycosides and to methods of using such oligosaccharide glycosides to modulate cell-mediated immune responses in a mammal.

REFERENCE TO PROVISIONAL APPLICATION 
This application claims the benefit of U.S. Provisional Application Ser. 
No. 60/006,593 filed Nov. 13, 1995. 
BACKGROUND OF THE INVENTION 
1. Field of the Invention 
This invention relates to novel oligosaccharide glycosides having mammalian 
immunosuppressive and/or tolerogenic properties. This invention also 
relates to pharmaceutical compositions comprising such oligosaccharide 
glycosides and to methods of using such oligosaccharide glycosides to 
modulate cell-mediated immune responses in a mammal. 
References 
The following references are cited in this application as superscript 
numbers at the relevant portion of the application: 
.sup.1 Brandley, et al., U.S. Pat. No. 5,143,712, issued Sep. 1, 1992, for 
"Method of Determining a Cite of Inflammation Utilizing ELAM-1 Ligands" 
.sup.2 Paulson, et al., International Patent Application Publication No. WO 
91/19502, published 26 Dec., 1991, for "Intercellular Adhesion Mediators" 
.sup.3 Lowe, et al., Cell, 63:475-485 (1990). 
.sup.4 Phillips, et al., Science, 250:1130-1132 (1990). 
.sup.5 Walz, et al., Science, 250:1132 et seq. (1990). 
.sup.6 Larsen, et al., Cell, 63:467-474 (1990). 
.sup.7 Ippolito, et al., U.S. patent application Ser. No. 07/714,161, filed 
Jun. 10, 1991 for "Immunosuppressive and Tolerogenic Oligosaccharide 
Glycosides". 
.sup.8 Ippolito, et al., U.S. patent application Ser. No. 07/889,017, filed 
May 26, 1992 for "Immunosuppressive and Tolerogenic Oligosaccharide 
Glycosides". 
.sup.9 Ippolito et al., U.S. patent application Ser. No. 08/081,214, filed 
Jun. 23, 1993 for "Time Dependent Administration of Oligosaccharide 
Glycosides Related to Blood Group Determinants Having a Type I or Type II 
Core Structure in Reducing Inflammation in a Sensitized Mammal Arising 
From Exposure to an Antigen". 
.sup.10 Ekborg, et al., Carbohydr. Res., 110:55-67 (1982). 
.sup.11 Dahmen, et al., Carbohydr. Res., 118:292-301 (1983). 
.sup.12 Rana, et al., Carbohydr. Res., 91:149-157 (1981). 
.sup.13 Amvam-Zollo, et al., Carbohydr. Res., 150:199-212 (1986). 
.sup.14 Paulsen, et al., Carbohydr. Res., 104:195-219 (1982). 
.sup.15 Chemyak, et al., Carbohydr. Res., 128:269-282 (1984). 
.sup.16 Fernandez-Santana, et al., J. Carbohydr. Chem., 8:531-537 (1989). 
.sup.17 Lee, et al., Carbohydr. Res., 37:193 et seq. (1974). 
.sup.18 Finan, et al., J. Chem. Soc., 3089 (1962). 
.sup.19 Paulsen, et al., Carbohydr. Res., 133:C1 (1984). 
.sup.20 BeMiller, et al., J. Carbohydr. Chem., 9:39 (1990). 
.sup.21 Lemieux, et al., Can. J. Chem., 57:1244 (1979). 
.sup.22 Lemieux, et al., Can. J. Chem., 60:63 (1982). 
.sup.23 Srivastava, et al., U.S. patent application Ser. No. 08/343,020, 
filed Nov. 21, 1994 for "Process for the Synthesis of3'-Substituted 
Lewis.sup.X Compounds". 
.sup.24 Banoub, et al., Can. J. Chem., 57:2091 (1979). 
.sup.25 Okamoto, et al., Tetrahedron, 46(17):5835-5837 (1990). 
.sup.26 Abbas, et al., Proc. Japanese-German Symp. Berlin, pp. 20-21 
(1988). 
.sup.27 Paulsen, Agnew. Chem. Int. Ed. Eng., 21:155-173 (1982). 
.sup.28 Schmidt, Agnew. Chem. Int. Ed. Eng., 25:212-235 (1986). 
.sup.29 Fugedi, et al., Glycoconj. J., 4:97-108 (1987). 
.sup.30 Kameyama, et al., Carbohydr. Res., 209:C.sub.1 -C.sub.4 (1991). 
.sup.31 Ratcliffe, et al., U.S. Pat. No. 5,079,353, issued Jan. 7, 1992 for 
"Sialic Acid Glycosides, Antigens, Immunoadsorbents, and Methods for Their 
Preparation" 
.sup.32 Ippolito, et al., U.S. patent application Ser. No. 08/081,212, 
filed Jun. 25, 1993 for "Immunosuppressive and Tolerogenic Modified 
Lewis.sup.C and LacNAc Compounds" 
.sup.33 Luengo, et al., Tetrahedron Lett., 33:6911 (1992) 
.sup.34 Carlsen, et al., J. Org. Chem., 46:3936 (1981) 
.sup.35 Unverzagt, et al., J. prakt. Chem., 334:570-578 (1992) 
.sup.36 Deter-Jusynski, et al., Carbohydr. Res., 28:61-74 (1973) 
The disclosures of each of the above-referenced publications, patents and 
patent applications are herein incorporated by reference in their entirety 
to the same extent as if each individual publication, patent or patent 
application was specifically and individually indicated to be incorporated 
by reference in its entirety. 
2. State of the Art 
A number of sialylated and sialylated/fucosylated oligosaccharide 
glycosides have been proposed as mediators of cell adhesion in that they 
are ligands for selectins (or LEC-CAM's).sup.3,4,5,6. Such selectins, 
including E-selectin, L-selectin and P-selectin, have been implicated as 
playing a seminal role in cell mediated inflammatory conditions and, 
heretofore, it has been postulated in the art that ligands for such 
selectins would possess anti-inflammatory properties.sup.1,2. In this 
regard, sialylated, fucosylated, and sialylated and fucosylated 
oligosaccharide structures relating to blood group determinants having a 
type I or a type II core structure, including Lewis.sup.X, Lewis.sup.A, 
sialyl Lewis.sup.X and sialyl Lewis.sup.A, have been shown by Ippolito et 
al..sup.7,8 to possess in vivo immunomodulating and tolerogenic properties 
in mammals including anti-inflammatory immunomodulating properties. 
Additionally, modified Lewis.sup.X -OR, Lewis.sup.C -OR and LacNAc-OR 
compounds having a sulfate group, a phosphate group or a carboxylate 
containing group at the 2, 3 and/or 6-positions of the galactose unit have 
also been disclosed to possess immunosuppressive and tolerogenic 
properties..sup.9,23 In addition, synthetic procedures for the preparation 
of such modified compounds have been reported..sup.23 
Notwithstanding these disclosures in the art, additional carbohydrate 
structures having immunomodulating and tolerogenic properties in mammals 
would provide valuable structure activity relationships and, in their own 
right, would be useful in providing anti-inflammatory immunomodulating 
properties. 
SUMMARY OF THE INVENTION 
This invention provides novel oligosaccharide glycosides which are useful 
for modulating cell mediated immune responses in a mammal, including cell 
mediated and immune directed inflammatory responses to an antigen in a 
sensitized mammal. 
The oligosaccharide glycosides of this invention are represented by Formula 
I and II below: 
##STR1## 
wherein: Y is oxygen, sulfur or --NH--; 
R is an aglycon of at least 1 carbon atom; 
R.sup.1 is selected from the group consisting of --OH, NH.sub.2, --N.sub.3, 
--NHC(O)R.sup.6, and -fuc(C)amido, wherein R.sup.6 is selected from the 
group consisting of 
alkyl of from 1 to 6 carbon atoms, 
cycloalkyl of from 3 to 8 carbon atoms, 
aryl of from 6 to 14 carbon atoms, 
alkaryl of from 7 to 20 carbon atoms, 
heteroaryl of from 2 to 5 carbon atoms and from 1 to 3 hetero atoms 
selected from the group consisting of nitrogen, sulfur and oxygen, 
substituted alkl of from 1 to 6 carbon atoms having one to three 
substituents independently selected from the group consisting of halo, 
nitro, cyano, carboxyl, amino, alkylamine of from 1 to 6 carbon atoms, 
alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, thioalkoxy of from 1 
to 6 carbon atoms and --C(O)R.sup.7 where R.sup.7 is selected from the 
group consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, 
substituted aryl of from 6 to 14 carbon atoms having one to three 
substituents independently selected from the group consisting of halo, 
nitro, cyano, carboxyl, amino, alkyl of from 1 to 6 carbon atoms, alkoxy 
of from 1 to 6 carbon atoms, thiol, hydroxyl, thioalkoxy of from 1 to 6 
carbon atoms and --C(O)R.sup.6 where R.sup.6 is selected from the group 
consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, and 
substituted alkyl having from 7 to 20 carbon atoms and having one to three 
substituents on the aryl moiety independently selected from the group 
consisting of halo, nitro, cyano, carboxyl, amino, alkyl of from 1 to 6 
carbon atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, 
thioalkoxy of from 1 to 6 carbon atoms and --C(O)R.sup.7 where R.sup.7 is 
selected from the group consisting of hydrogen and alkyl of from 1 to 6 
carbon atoms, 
substituted heteroaryl of from 2 to 5 carbon atoms and from 1 to 3 hetero 
atoms selected from the group consisting of nitrogen, sulfur and oxygen 
having one to three substituents independently selected from the group 
consisting of halo, nitro, cyano, carboxyl, amino, alkyl of from 1 to 6 
carbon atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, 
thioalkoxy of from 1 to 6 carbon atoms and --C(O)R.sup.7 where R.sup.7 is 
selected from the group consisting of hydrogen and alkyl of from 1 to 6 
carbon atoms; 
R.sup.2 is selected from the group consisting of hydrogen, hydroxyl, halo, 
--OSO.sub.3 H and --OP(O)(OH).sub.2 ; 
R.sup.3 is selected from the group consisting of hydrogen, hydroxyl, halo, 
--OSO.sub.3 H and --OP(O)(OH).sub.2 ; 
R.sup.4 is selected from the group consisting of hydroxyl, halo and 
--O-L-fucosyl; 
R.sup.5 is selected from the group consisting of hydrogen, L-fucose and 
L-fucose substituted at the 2, 3, and/or 4-positions with a substituent 
selected from the group consisting of halo, hydrogen, alkoxy, --OSO.sub.3 
H and --OP(O)(OH).sub.2 ; 
R.sup.7 is selected from the group consisting of hydrogen, hydroxy, 
--OS(O).sub.3 H, --OP(O)(OH).sub.2, halo, azido, --NH.sub.2, 
--NHC(O)R.sup.6, and -fuc(C)amido, wherein R.sup.6 is selected from the 
group consisting of 
alkly of from 1 to 6 carbon atoms, 
cyclokyl of from 3 to 6 carbon atoms, 
aryl of from 6 to 14 carbon atoms, 
alkaryl of from 7 to 20 carbon atoms, 
heteroaryl of from 1 to 8 carbon atoms and from 1 to 4 hetero atoms 
selected from the group consisting of nitrogen, sulfur and oxygen, 
heterocyclic of from 1 to 8 carbon atoms and from 1 to 4 hetero atoms 
selected from nitrogen, sulfur or oxygen within the ring 
substituted alkyl of from 1 to 6 carbon atoms having one to three 
substituents independently selected from the group consisting of halo, 
nitro, cyano, carboxyl, amino, alkylamine of from 1 to 6 carbon atoms, 
alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, thioalkoxy of from 1 
to 6 carbon atoms and --C(O)R.sup.7 where R.sup.7 is selected from the 
group consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, 
substituted aryl of from 6 to 14 carbon atoms having one to three 
substituents independently selected from the group consisting of halo, 
nitro, cyano, carboxyl, amino, alkyl of from 1 to 6 carbon atoms, alkoxy 
of from 1 to 6 carbon atoms, thiol, hydroxyl, thioalkoxy of from 1 to 6 
carbon atoms and --C(O)R.sup.7 where R.sup.7 is selected from the group 
consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, and 
substituted alkaryl having from 7 to 20 carbon atoms and having one to 
three substituents on the aryl moiety independently selected from the 
group consisting of halo, nitro, cyano, carboxyl, amino, alkyl of from 1 
to 6 carbon atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, 
thioalkoxy of from 1 to 6 carbon atoms and --C(O)R.sup.7 where R.sup.7 is 
selected from the group consisting of hydrogen and alkyl of from 1 to 6 
carbon atoms, 
substituted heteroaryl of from 2 to 5 carbon atoms and from 1 to 3 hetero 
atoms selected from the group consisting of nitrogen, sulfur and oxygen 
having one to three substituents independently selected from the group 
consisting of halo, nitro, cyano, carboxyl, amino, alkyl of from 1 to 6 
carbon atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, 
thioalkoxy of from 1 to 6 carbon atoms and --C(O)R.sup.7 where R.sup.7 is 
selected from the group consisting of hydrogen and alkyl of from 1 to 6 
carbon atoms; 
and X is selected from the group consisting of hydroxyl, chloro, 
--OSO.sub.3 H or --OP(O)(OH).sub.2, 
and pharmaceutically acceptable salts thereof 
with the proviso that when R.sup.2 is hydroxyl, R.sup.1 is --OH, NH.sub.2, 
--N.sub.3 or --NHC(O)R.sup.6 where R.sup.6 is alkyl of from 1 to 4 carbon 
atoms, R.sup.5 is hydrogen, L-fucosyl, 4-sulfo-L-fucosyl or 
4-phospho-L-fucosyl, R.sup.7 is hydrogen, hydroxy, --OS(O).sub.3 H, azido, 
--NH.sub.2, --NHC(O)R.sup.6 where R.sup.6 is alkyl of from 1 to 4 carbon 
atoms, and X is hydroxy, --OSO.sub.3 H or --OP(O)OH.sub.2 and 
pharmaceutical salts thereof, then R.sup.3 is not hydroxyl, --OSO.sub.3 H 
or --OP(O)(OH).sub.2 and pharmaceutical salts thereof. 
In particular, the compounds disclosed in either International Patent 
Application Nos. WO 92/22564 and WO 93/24506 are specifically excluded 
from the compounds of formula I and II of this application. 
Preferably, R is an aglycon of from 1 to 20 carbon atoms, more preferably R 
is an aglycon of from 1 to 10 carbon atoms and still more preferably is 
selected from the group consisting of --(CH.sub.2).sub.8 COOCH.sub.3, 
--(CH.sub.2).sub.5 OCH.sub.2 CH.dbd.CH.sub.2 and --(CH.sub.2).sub.8 
CH.sub.2 OH. 
Preferably, R.sup.1 is fuc(C)amido or --NHC(O)R.sup.6 where R.sup.6 is 
alkyl containing 1 to 4 carbon atoms, cycloalkyl containing 5 or 6 carbon 
atoms, phenyl, substituted phenyl having one or two substituents 
independently selected from acetyl, nitro, or amino. More preferably, 
R.sup.1 is --NHC(O)R.sup.6 where R.sup.6 is phenyl, o-nitrophenyl and 
p-nitrophenyl. 
R.sup.2 is preferably selected from the group consisting of hydroxyl, 
chloro and hydrogen. More preferably, R.sup.2 is hydroxyl or hydrogen. 
Preferably, R.sup.3 is selected from the group consisting of hydroxy, 
chloro and deoxy. More preferably, R.sup.3 is chloro or deoxy. 
R.sup.5 is preferably L-fucose. 
X is preferably --OSO.sub.3 H, --OP(O)OH).sub.2 or a pharmaceutically 
acceptable salt thereof. More preferably, X is --OSO.sub.3 H or a 
pharmaceutically acceptable salt thereof. 
Preferred compounds for use in this invention include, by way of example, 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O 
-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-o-acetylbenzamido-3-O-(.alpha.-L-fucopyranosyl)-4- 
O-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-cyclohexamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3 
-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-fuc(C)amido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O 
-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-4-O-(.beta.-D-galactopyranosyl)-2 
-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-4-O-(4-O-sulfo-.beta.-D-galactopyranosyl)-.beta.-D-g 
lucopyranoside 
8-methoxycarbonyloctyl-4-O-(4-O-phospho-.beta.-D-galactopyranosyl)-.beta.-D 
-glucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3,4,6 
-tri-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-2-O-(.alpha.-L-fucopyranosyl)-.beta.-D-galactopyranosyl!-2-deoxy-.beta 
.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-chl 
oro-6-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-2-deoxy-.beta.-D-glucopyr 
anoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-deo 
xy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4-chl 
oro-4-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyra 
noside 
8-methoxycarbonyloctyl-2-acetamido-3-O-.alpha.-L-fucopyranosyl)-4-O-4,6-di 
chloro-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-gl 
ucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-d 
ideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosid 
e 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl azide 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl amine 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl benzamide 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl p-nitrobenzamide 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl butyramide 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl acetamide 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl stearamide 
2-acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl L-serine 
2-acetamnido-2-deoxy-3-O-(4-deoxy-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo-. 
beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(4-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-methyl-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulf 
o-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside 
phenylalanine 
amido-2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-.beta.-D- 
glucopyranoside 
2-benzamido-2-deoxy-3-O-(4-deoxy-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo-.b 
eta.-D-galactopyranosyl)-.beta.-D-glucopyranosyl benzamide 
cyclohexylalanine 
amido-2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-.beta.-D- 
glucopyranoside 
tryptophanamido-2-fuc(C)-amido-4-O-(3-O-sulfo-.beta.-D-galactopyranosyl)-.b 
eta.-D-glucopyranoside 
acetamido-2-(fuc(C)-amido-4-O-3-O-sulfo-.beta.-D-galactopyranosyl)-2-deoxy 
-.beta.-D-glucopyranoside 
benzamido 
2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!)-2-deoxy-.beta. 
-D-glucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-6-O-sulfo-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl 
2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dichloro-dideoxy-3-O-su 
lfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyrano 
side 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-d 
ideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.- 
D-glucopyranoside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-6-amino-2,6-dideoxy-.beta.-D-glucopyranosid 
e 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyran 
oside 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-.beta.-D-galacto-pyranosyl!-6-chloro-2,6-dideoxy-.beta.-D-glucopyranos 
ide 
2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dichloro-dideoxy-3-O-sul 
fo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide 
2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dideoxy-3-O-sulfo-.beta. 
-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide 
2-benzamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranoside benzamide 
8-methoxycarbonyloctyl-2-amino-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dichl 
oro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyra 
noside 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-d 
ichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-gluco 
pyranoside 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-d 
ideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosid 
e 
8-methoxycarbonyloctyl-2-amino-4-O-(.alpha.-L-fucopyranosyl)-3-O-3-O-sulfo 
-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-benzamido-4-O-(.alpha.-L-fucopyranosyl)-3-O-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-4-O-(.alpha.-L-fucopyranosyl)-3-O 
-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
8-methoxycarbonyloctyl-2-(fuc(c)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyra 
nosyl!-2-deoxy-.beta.-D-glucopyranoside 
as well as pharmaceutically acceptable salts thereof and further including 
the above compounds wherein the aglycon is replaced by an aglycon of from 
1 to 20 carbon atoms. 
This invention further provides a pharmaceutical composition suitable for 
administration to a mammal which composition comprises a pharmaceutically 
inert carrier and an effective inflammation-reducing amount of an 
oligosaccharide glycoside of Formula I or II. 
This invention additionally provides a method of reducing antigen-induced 
inflammation in a mammal which method comprises administering to said 
mammal an effective inflammation-reducing amount of a oligosaccharide 
glycoside of Formula I or II.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
This invention is directed to novel oligosaccharide glycosides having 
mammalian immunosuppressive and tolerogenic properties. 
However, prior to discussing this invention in further detail, the 
following terms will first be defined. 
Definitions 
As used herein the following terms have the definitions given below: 
The term "cell-mediated immune response in a mammal" refers to those 
mammalian immune responses which are mediated by cell--cell interactions. 
Included within this term are cell mediated inflammatory responses to an 
antigen such as DTH responses as well as cell-mediated inflammatory 
responses arising from injury such as frost-bite injury, reperfusion 
injury, adult respiratory distress syndrome, and the like. Preferably, the 
cell-mediated immune response is a leucocyte-mediated response. 
The term "antigen" refers to any protein, peptide, carbohydrate, nucleic 
acid or other non-endogenous substance which when exposed to a mammal 
induces an immune response in that mammal. 
Disease conditions caused by antigen exposure include, by way of example, 
psoriasis, asthma, dermatitis, rheumatoid arthritis, delayed type 
hypersensitivity, inflammatory bowel disease, multiple sclerosis, viral 
pneumonia, bacterial pneumonia, and the like. 
The term "sensitized mammal" or "antigen-sensitized mammal" refers to those 
mammals which have been previously exposed to an antigen and, accordingly, 
their immune systems have become educated to that antigen. Typically, 
initial exposure of an antigen to a mammal primes or educates the mammal's 
immune response to later exposure to that antigen with minimal 
inflammation during such initial exposure. 
The term "secondary immune response" refers to the effector phase of a 
mammal's immune response to an antigen to which it has been previously 
been sensitized. A mammal's secondary immune response is typically 
accompanied by inflammation at the point of antigen exposure. 
The term "period for maximal inflammation" refers to the period of time 
typically required to achieve maximal inflammation to a specific antigen 
exposure. This period of time depends on several factors such as the 
specific antigen to which the mammal has been exposed, the particular 
mammalian species exposed to the antigen, etc. Accordingly, the period of 
time required to effect maximal antigen induced inflammation in a 
sensitized mammal will vary for, by way of example, asthma as opposed to 
rheumatoid arthritis. 
The term "Lewis.sup.X " or "Le.sup.x " refers to the trisaccharide 
.beta.Gal(1.fwdarw.4).beta.Fuc(1.fwdarw.3).beta.GlcNAc. 
The term "Lewis.sup.C " or "Le.sup.c " refers to the disaccharide 
.beta.Gal(1.fwdarw.3).beta.GlcNAc. 
The term "aglycon of at least one carbon atom" refers to non-saccharide 
containing residues having at least one carbon atom. Preferably, the 
aglycon moiety, R, has from 1 to 20 carbon atoms or is selected from the 
group consisting of --(A)--Z wherein A represents a covalent bond, an 
alkylene group of from 2 to 10 carbon atoms, a moiety of the formula 
--(CH.sub.2 CR.sup.8 R.sup.8).sub.n --, and a moiety of the formula 
--(CH.sub.2 CR.sup.8 R.sup.8 G).sub.n -- wherein n is an integer equal to 
1 to 5, each R.sup.8 is independently selected from the group consisting 
of hydrogen, alkyl of from 1 to 6 carbon atoms, phenyl and phenyl 
substituted with 1 to 3 substituents selected from the group consisting of 
amine, hydroxyl, halo, alkyl of from 1 to 4 carbon atoms and alkoxy of 
from 1 to 4 carbon atoms and G is selected from the group consisting of 
--O--, --S-- and --NH--; and Z is selected from the group consisting of 
hydrogen, methyl, phenyl, nitrophenyl, aminophenyl and, when G is not 
oxygen, sulfur or nitrogen and A is not a bond, then Z is also selected 
from the group consisting of --OH, --SH, --NH.sub.2, --NHR.sup.9, 
--N(R.sup.9).sub.2, --C(O)OH, --C(O)OR.sup.9, --C(O)NH--NH.sub.2, 
--C(O)NH.sub.2, --C(O)NHR.sup.9, --C(O)N(R.sup.9).sub.2, and --OR.sup.10 
wherein each R.sup.9 is independently alkyl of from 1 to 4 carbon atoms 
and R.sup.10 is an alkenyl group of from 3 to 10 carbon atoms. 
Numerous aglycons are known in the art. For example, an aglycon comprising 
a para-nitrophenyl group (i.e., --YR=--OC.sub.6 H.sub.4 -p-NO.sub.2) has 
been disclosed by Ekborg, et al..sup.10 At the appropriate time during 
synthesis, the nitro group is reduced to an amino group which can be 
protected as N-tifluoroacetamido. The trifluoroacetamido group can later 
be removed thereby unmasking the amino group which can then be used to 
further functionalize the aglycon group. 
An aglycon containing sulfur is disclosed by Dahmen, et al..sup.11 
Specifically, this aglycon is derived from a 2-bromoethyl group which, in 
a substitution reaction with thionucleophiles, has been shown to lead to 
aglycons possessing a variety of terminal functional groups such as 
--YCH.sub.2 CH.sub.2 SCH.sub.2 CO.sub.2 CH.sub.3 and --YCH.sub.2 CH.sub.2 
SC.sub.6 H.sub.4 -p-NH.sub.2. 
Rana, et al.12 discloses a 6-trifluoroacetamidohexyl aglycon 
(--Y--(CH.sub.2).sub.6 --NHCOCF.sub.3) in which the trifluoroacetamido 
protecting group can be removed unmasking the primary amino group which 
can then be used to further functionalize the aglycon group. 
Other exemplification of known aglycons include the 
7-methoxycarbonyl-3,6-dioxaheptyl aglycon.sup.13 (--YCH.sub.2 
--CH.sub.2)OCH.sub.2 CO.sub.2 CH.sub.3 ; the 
2-(4-methoxycarbonylbutanecarboxamido)ethyl.sup.14 (--YCH.sub.2 CH.sub.2 
NHC(O)(CH.sub.2).sub.4 CO.sub.2 CH.sub.3); and the allyl aglycon.sup.15 
(--YCH.sub.2 CH.dbd.CH.sub.2) which, by radical co-polymerization with an 
appropriate monomer, leads to co-polymers; other allyl aglycons.sup.16 are 
known e.g., --Y(CH.sub.2 CH.sub.2 O).sub.2 CH.sub.2 CH.dbd.CH.sub.2 !. 
Additionally, allyl aglycons can be derivatized in the presence of 
2-aminoethane-thiol.sup.17 to provide for aglycons --YCH.sub.2 CH.sub.2 
CH.sub.2 SCH.sub.2 CH.sub.2 NH.sub.2. Still other aglycons are illustrated 
hereinbelow. 
Additionally, as shown by Ratcliffe et al..sup.31, the R group can be an 
additional saccharide-OR.sup.11 or an oligosaccharide-OR.sup.11 containing 
an aglycon at the reducing sugar terminus. 
Still further, when Y is --NH--, the aglycon can be the residue of an amino 
acid or a peptide of from 2 to 10 amino acids in length. Amino acids 
include any of the naturally occurring amino acids, as well as synthetic 
analogs and derivatives thereof. .alpha.-Amino acids comprise a carbon 
atom to which is bonded an amino group, a carboxyl group, a hydrogen atom, 
and a distinctive group referred to as a "side chain". The side chains of 
naturally occurring amino acids are well known in the art and include, for 
example, hydrogen (e.g., as in glycine), alkyl (e.g., as in alanine, 
valine, leucine, isoleucine, proline), substituted alkyl (e.g., as in 
threonine, serine, methionine, cysteine, aspartic acid, asparagine, 
glutamic acid, glutamine, arginine, and lysine), arylalkyl (e.g., as in 
phenylalanine and tryptophan), substituted arylalkyl (e.g., as in 
tyrosine), and heteroarylalkyl (e.g., as in histidine). 
One of skill in the art will appreciate that the term "amino acid" can also 
include .beta.-, .gamma.-, .delta.-, and .omega.-amino acids, and the 
like. Unnatural amino acids are also known in the art, as set forth in, 
for example, Williams (ed.), Synthesis of Optically Active .alpha.-Amino 
Acids, Pergamon Press (1989); Evans et al., J. Amer. Chem. Soc., 
112:4011-4030 (1990); Pu et al., J. Amer. Chem. Soc., 56:1280-1283 (1991); 
and Williams et al., J. Amer. Chem. Soc., 113:9276-9286 (1991) which are 
incorporated herein by reference in their entirety. 
As used herein, the twenty conventional amino acids and their abbreviations 
follow conventional usage. Amino acid residues are abbreviated as follows: 
Phenylalanine is Phe or F; Leucine is Leu or L; Isoleucine is Ile or I; 
Methionine is Met or M; Norleucine is Nle; Valine is Val or V; Serine is 
Ser or S; Proline is Pro or P; Threonine is Thr or T; Alanine is Ala or A; 
Tyrosine is Tyr or Y; Histidine is His or H; Glutamine is Gln or Q; 
Asparagine is Asn or N; Lysine is Lys or K; Aspartic Acid is Asp or D; 
Glutamic Acid is Glu or E; Cysteine is Cys or C; Tryptophan is Trp or W; 
Arginine is Arg or R; Glycine is Gly or G, and X is any amino acid. 
Stereoisomers (e.g., D-amino acids) of the twenty conventional amino 
acids, unnatural amino acids such as .alpha.,.alpha.-disubstituted amino 
acids, N-alkyl amino acids, and other unconventional amino acids are also 
suitable components for compounds described herein. Examples of 
unconventional amino acids include: 4-hydroxyproline, O-phosphoserine, 
N-acetylserine, N-formylmethionine, 3-methylhistidine, 5-hydroxylysine, 
and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In 
the polypeptide notation used herein, the left-hand direction is the amino 
terminal direction and the right-hand direction is the carboxy-terminal 
direction, in accordance with standard usage and convention. 
Preferably, the aglycon moiety is a hydrophobic group and most preferably, 
the aglycon moiety is a hydrophobic group selected from the group 
consisting of --(CH.sub.2).sub.8 COOCH.sub.3, --(CH.sub.2).sub.5 OCH.sub.2 
CH.dbd.CH.sub.2 and --(CH.sub.2).sub.8 CH.sub.2 OH. 
The term "oligosaccharide" refers to a carbohydrate structure having from 2 
to about 7 saccharide units. The particular saccharide units employed are 
not critical and include, by way of example, all natural and synthetic 
derivatives of glucose, galactose, N-acetylglucosamine, 
N-acetylgalactosamine, fucose, sialic acid, 3-deoxy-D,L-octulosonic acid, 
and the like. In addition to being in their pyranose form, all saccharide 
units described herein are in their D form except for fucose which is in 
its L form. 
The term "pharmaceutically acceptable salts" includes the pharmaceutically 
acceptable addition salts of the compounds of Formula I or Formula II 
derived from a variety of organic and inorganic counter salts well known 
in the art and include, by way of example only, sodium, potassium, 
calcium, magnesium, ammonium, tetralkylammonium, chloride, fluoride, 
bromide, hydroxide and the like. 
The term "sulfate" refers to the --O--S(O.sub.2)--OH group, which readily 
forms pharmaceutically acceptable salts thereof. 
The term "phosphate" refers to the group --O--P(O)--OH.sub.2, which readily 
forms pharmaceutically acceptable salts thereof (e.g., --O--P(O)--(O.sup.- 
Na.sup.+).sub.2). 
The term "removable blocking group" or "blocking group" or "protecting 
group" refers to any group which when bound to one or more hydroxyl and/or 
amine groups of oligosaccharide glycoside compounds and oligosaccharide 
glycoside related compounds prevents reactions from occurring at these 
hydroxyl and/or amine groups and which protecting group can be removed by 
conventional chemical or enzymatic steps to reestablish the hydroxyl or 
amine group. Typically, the particular removable blocking group employed 
is not critical and preferred removable hydroxyl blocking groups include 
conventional substituents such as benzyl, acetyl, benzoyl, chloroacetyl, 
benzylidene, t-butyldiphenylsilyl, t-butyldimethylsilyl and any other 
group that can be introduced either enzymatically or chemically onto a 
hydroxyl functionality and later selectively removed either by enzymatic 
or chemical methods in mild conditions compatible with the nature of the 
product. Preferred amine blocking groups include these well known in the 
art such as carboxybenzyloxy (CBZ), t-butyloxy carbonyl (t-Boc), and any 
other group that can be introduced either enzymatically or chemically onto 
an amine functionality and later selectively removed either by enzymatic 
or chemical methods in mild conditions compatible with the nature of the 
product. 
"Alkyl" refers to monovalent alkyl groups having from 1 to 6 carbon atoms. 
This term is exemplified by groups such as methyl, ethyl, n-propyl, 
iso-propyl, n-butyl, iso-butyl, n-hexyl, and the like. 
"Alkylene" refers to divalent alkylene groups preferably having from 1 to 
10 carbon atoms and more preferably 2 to 10 carbon atoms. This term is 
exemplified by groups such as methylene (--CH.sub.2 --), ethylene 
(--CH.sub.2 CH.sub.2 --), the propylene isomers (e.g., --CH.sub.2 CH.sub.2 
CH.sub.2 -- and --CH(CH.sub.3)CH.sub.2 --) and the like. 
"Alkaryl" refers to -alkylene-aryl groups of from 7 to 20 carbon atoms 
preferably having from 1 to 10 carbon atoms in the alkylene moiety and 
from 6 to 10 carbon atoms in the aryl moiety. Such alkaryl groups are 
exemplified by benzyl, phenethyl and the like. 
"Alkoxy" refers to the group "alkyl--O--". Preferred alkoxy groups include, 
by way of example, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, 
tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the 
like. 
"Aryl" refers to an unsaturated aromatic carbocyclic group of from 6 to 14 
carbon atoms having a single ring (e.g., phenyl) or multiple condensed 
rings (e.g., naphthyl or anthryl). Preferred aryls include phenyl, 
naphthyl and the like. 
"Cycloalkyl" refers to cyclic alkyl groups of from 3 to 8 carbon atoms 
having a single cyclic ring or multiple condensed rings which can be 
optionally substituted with from 1 to 3 alkyl groups. Preferred cycloalkyl 
groups include those having from 3 to 6 carbon atoms. Such cycloalkyl 
groups include, by way of example, single ring structures such as 
cyclopropyl, cyclobutyl, cyclopentyl, cyclooctyl, 1-methylcyclopropyl, 
2-methylcyclopentyl, 2-methylcyclooctyl, and the like, or multiple ring 
structures such as adamantanyl, and the like. 
"Halo" or "halogen" refers to fluoro, chloro, bromo and iodo and preferably 
is either chloro or bromo. 
"Heteroaryl" refers to a monovalent aromatic carbocyclic group of from 1 to 
8 carbon atoms and 1 to 4 heteroatoms selected from oxygen, nitrogen and 
sulfur within the ring. Preferred heteroaryl groups have from 2 to 5 
carbon atoms and 1 to 3 heteroatoms selected from oxygen, nitrogen and 
sulfur. 
"Heterocycle" or "heterocyclic" refers to a monovalent saturated or 
unsaturated group having a single ring or multiple condensed rings, from 1 
to 8 carbon atoms and from 1 to 4 hetero atoms selected from nitrogen, 
sulfur or oxygen within the ring. 
Unless otherwise constrained by the definition for the heterocyclic 
substituent, such heterocyclic groups can be optionally substituted with 1 
to 3 substituents selected from the group consisting of alkyl, alkoxy, 
aryl, aryloxy, halo, nitro, heteroaryl, thioalkoxy, thioaryloxy and the 
like. Such heterocyclic groups can have a single ring or multiple 
condensed rings. 
Examples of nitrogen heterocycles and heteroaryls include, but are not 
limited to, pyrrole, imidazole, pyrazole, pyridine, pyrazine, pyrimidine, 
pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, 
isoquinoline, quinoline, phthalazine, naphthylpyridine, quinoxaline, 
quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, 
acridine, phenanthroline, isothiazole, phenazine, isoxazole, phenoxazine, 
phenothiazine, imidazolidine, imidazoline, piperidine, piperazine, 
indoline and the like. 
"Thiol" refers to the group --SH. 
"Thioalkoxy" refers to the groups --S-alkyl. 
General Synthetic Methodology 
Chemical methods for the synthesis of the oligosaccharides are known in the 
art. These oligosaccharides are generally assembled using suitably 
protected individual monosaccharides and/or suitably protected individual 
disaccharides intermediates. 
The specific methods employed are generally adapted and optimized for each 
individual structure to be synthesized. In general, the chemical synthesis 
of all or part of these oligosaccharides first involves formation of a 
glycosidic linkage on the anomeric carbon atom of the reducing sugar. 
Specifically, an appropriately protected form of a naturally occurring or 
of a chemically modified glucose structure (the glycosyl donor) is 
selectively modified at the anomeric center of the reducing unit so as to 
introduce a leaving group comprising halides, trichloroacetimidate, 
acetyl, thioglycoside, etc. The donor is then reacted under catalytic 
conditions well known in the art with an aglycon or an appropriate form of 
a carbohydrate acceptor which possess one free hydroxyl, free thiol or 
primary/secondary amino group at the position where the glycosidic linkage 
is to be established. A large variety of aglycon moieties are known in the 
art and can be attached with the proper configuration to the anomeric 
center of the reducing unit. Appropriate use of compatible blocking 
groups, well known in the art of carbohydrate synthesis, will allow 
selective modification of the synthesized structures or the further 
attachment of additional sugar units or sugar blocks to the acceptor 
structures. 
After formation of the glycosidic linkage, the saccharide glycoside can be 
used to effect coupling of additional saccharide unit(s) or chemically 
modified at selected positions or, after conventional deprotection, used 
in an enzymatic synthesis. In general, chemical coupling of a naturally 
occurring or chemically modified saccharide unit to the saccharide 
glycoside is accomplished by employing established chemistry well 
documented in the literature. See, for example, Okamoto et al..sup.25, 
Abbas et al..sup.26, Paulsen.sup.27, Schmidt.sup.28, Fugedi et al..sup.29, 
Kameyama et al..sup.30 and Ratcliffe, et al..sup.31 
The figures attached hereto illustrate a variety of complete chemical 
synthetic schemes used for preparing representative oligosaccharide 
glycosides of this invention. By necessity, these schemes illustrate the 
synthesis of specific compounds of this invention. However, it is well 
within the skill of those in the art to adapt these synthetic schemes to 
prepare any of the compounds of this invention. Moreover, it will be 
appreciated by those skilled in the art that where typical or preferred 
process conditions (e.g., reaction temperatures, times, mole ratios of 
reactants, solvents, pressures, etc.) are given, other process conditions 
may also be used unless otherwise stated. Optimum reaction conditions may 
vary with the particular reactants or solvents used, but such conditions 
can be determined by one skilled in the art by routine optimization 
procedures. 
A. 2-Amino and 2-Amido 3'-Sulfo Lewis.sup.X -OR Derivatives 
FIG. 1 illustrates the synthesis of 2-substituted 3'-sulfo Lewis.sup.X 
derivatives. As shown in this figure, 3'-sulfo-Lewis.sup.X derivatives 
having an amino or an amido substituent at the 2-position are prepared 
beginning with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-.alpha.-D-glucopyranosyl 
bromide (1'), the synthesis of which is known in the art.sup.19-20. 
Compound 1' is first converted to the aglycon by reaction with from about 
1.1 to about 5 equivalents of HYR, e.g., HO(CH.sub.2).sub.8 COOCH.sub.3, 
by well known chemistry. In a preferred embodiment, compound 1' is reacted 
with 8-methoxycarbonyloctanol in anhydrous dichloromethane containing 
molecular sieves and a catalyst, such as silver carbonate, to provide 
intermediate 1" in 90% yield as a crystalline solid. This reaction is 
generally conducted at a temperature ranging from -20.degree. C. to 
-10.degree. C. for a period of 3 to 4 hours. 
The 3, 4 and 6 hydroxyl groups of compound 1" are then deprotected by 
reaction of compound 1" with sodium methoxide in methanol to give 
8-methoxycarbonyloctyl-2-azido-2-deoxy-.beta.-D-glucopyranoside (1a). 
The 4 and 6 hydroxy groups of compound 1a are then protected as the 
4,6-O-benzylidene derivative by reaction of compound 1a with benzaldehyde 
dimethylacetal in the presence of an acid catalyst, such as 
p-toluenesulfonic acid, to give compound 1. This reaction is typically 
conducted at room temperature in an anhydrous inert solvent, such as 
acetonitrile, and is generally complete in about 0.5 to 5 hours. 
The unprotected hydroxyl group of compound 1 is then glycosylated with 
p-chlorophenyl tribenzyl thiofucose (2). Compound 2 is well known in the 
art and may be prepared by the procedures described by Srivastava et 
al..sup.23 The glycosylation reaction is typically conducted by contacting 
compound 1 with about 1 to 2 equivalents, preferably 1.2 equivalents, of 
compound 2 in the presence of a cupric bromide/dimethylformamide catalyst 
and tetraethylammonium bromide. This reaction is generally conducted at 
room temperature in an anhydrous inert solvent, such dichloromethane, 
containing molecular sieves. The reaction is typically complete after 
about 7 to 15 hours and provides compound 3. 
The 4,6-O-benzylidene group of compound 3 is then opened regioselectively 
to provide compound 4 having an unblocked hydroxyl group at the 4 
position. Regioselective opening of the benzylidene group is affected by 
treatment of compound 3 with at least a molar equivalent, preferably an 
excess, of sodium cyanoborohydride or a similar hydride reducing agent, in 
the presence of an ethereal solution of hydrochloric acid. The reaction is 
typically conducted in a suitable inert solvent, such as tetrahydrofuran, 
and is preferably maintained under anhydrous conditions by, for example, 
the inclusion of molecular sieves. A pH indicator, such a methyl orange, 
is generally added to the reaction system and the reaction is generally 
conducted at a pH of about 3 or less. The reaction conditions are not 
critical and the conditions are selected so as to produce compound 4. In a 
preferred embodiment, about 2 to about 20, preferably 5 to 10 equivalents 
of sodium cyanoborohydride is employed at a reaction temperature of from 
about -15.degree. C. to about 20.degree. C. (preferably 0.degree. C.) for 
a period of from about 1 to about 7 hours. The reaction generally provides 
compound 4 in about 60% yield. 
Compound 4 is next converted to 
8-methoxycarbonyloctyl-2-azido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-(.beta.-D-galactopyranosyl)-6-O-benzyl-2-deoxy-.beta.-D-glucopyra 
noside (7) by reaction with from about 1.1 to about 2 equivalents of 
O-(2,3,4,6-tetra-O-acetyl-.alpha.-D-galactopyranosyl)-trichloroacetirnidat 
e (5) using conventional coupling conditions, followed by deacetylation of 
the resulting trisaccharide. 
The coupling reaction is preferably conducted using an excess of boron 
trifluoride etherate relative to the galactose imidate and preferably 
using from about 1.1 to about 2 equivalents. The reaction is typically 
conducted at from about -30.degree. C. to about 10.degree. C. (preferably 
-10.degree. C. to 0.degree. C.) in a suitable anhydrous organic solvent 
such as dichloromethane or a 1:2 mixture of dichloromethane:ether. 
Deacetylation is conducted using conventional reaction conditions, 
preferably using sodium methoxide in methanol, to provide compound 7. 
The galactose unit of compound 7 is next converted to the 4,6-O-benzylidene 
derivative compound 8 by reaction of compound 7 with from about 1 to about 
2 equivalents of benzaldehyde dimethylacetal. This reaction is preferably 
conducted in an inert organic solvent, such as acetonitrile, in the 
presence of an acidic catalyst, such as p-toluenesulfonic acid (pTSA). In 
a preferred embodiment, the reaction is conducted at a temperature of from 
about 0.degree. C. to about 35.degree. C. (preferably 15.degree. C. to 
25.degree.) for from about 1 to about 5 hours. Standard work-up procedures 
provide compound 8 in about 76% yield. 
The 2-azido group of compound 8 is then reduced to an amino group by 
contacting compound 8 with a saturated solution of hydrogen sulfide in a 
suitable solvent. In a preferred embodiment, the solvent comprises 
pyridine (2 parts), triethylamine (0.05 parts) and water (0.05 parts). 
This reaction is preferably conducted initially at 0.degree. C. for about 
2 hours and then at room temperature for about 5 to 15 hours, preferably 
for about 15 hours, to provide the amino derivative 9. 
The amino group of 
8-methoxycarbonyloctyl-2-amino-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy- 
.beta.-D-glucopyranoside (9) can then be acylated to form various 2-amido 
derivatives. Suitable acylating agents for use in this reaction include 
acyl halides, such as carboxylic acid chlorides and bromides; carboxylic 
acid anhydrides and carboxylic acids. 
Preferred acylating agents are those having the formula W--C(O)R.sup.6 
where W is chloro or hydroxyl and R.sup.6 is selected from the group 
consisting of alkyl of from 1 to 6 carbon atoms, cycloalkyl of from 3 to 8 
carbon atoms, heterocyclic, aryl of from 6 to 14 carbon atoms, alkaryl of 
from 7 to 20 carbon atoms, heteroaryl of from 1 to 8 carbon atoms and from 
1 to 4 hetero atoms selected from the group consisting of nitrogen, sulfur 
and oxygen, substituted alkyl of from 1 to 6 carbon atoms having one to 
three substituents independently selected from the group consisting of 
halo, nitro, cyano, carboxyl, amino, alkylamino of from 1 to 6 carbon 
atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, thioalkoxy of 
from 1 to 6 carbon atoms and --C(O)R.sup.6 where R.sup.6 is selected from 
the group consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, 
substituted aryl of from 6 to 14 carbon atoms having one to three 
substituents independently selected from the group consisting of halo, 
nitro, cyano, carboxyl, amino, alkyl of from 1 to 6 carbon atoms, alkoxy 
of from 1 to 6 carbon atoms, thiol, hydroxyl, thioalkoxy of from 1 to 6 
carbon atoms and --C(O)R.sup.6 where R.sup.6 is selected from the group 
consisting of hydrogen and alkyl of from 1 to 6 carbon atoms, and 
substituted alkaryl having from 7 to 20 carbon atoms and having one to 
three substituents on the aryl moiety independently selected from the 
group consisting of halo, nitro, cyano, carboxyl, amino, alkyl of from 1 
to 6 carbon atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, 
thioalkoxy of from 1 to 6 carbon atoms and --C(O)R.sup.6 where R.sup.6 is 
selected from the group consisting of hydrogen and alkyl of from 1 to 6 
carbon atoms, substituted heteroaryl of from 2 to 5 carbon atoms and from 
1 to 3 hetero atoms selected from the group consisting of nitrogen, sulfur 
and oxygen having one to three substituents independently selected from 
the group consisting of halo, nitro, cyano, carboxyl, amino, alkyl of from 
1 to 6 carbon atoms, alkoxy of from 1 to 6 carbon atoms, thiol, hydroxyl, 
thioalkoxy of from 1 to 6 carbon atoms and --C(O)R.sup.6 where R.sup.6 is 
selected from the group consisting of hydrogen and alkyl of from 1 to 6 
carbon atoms; is an alkyl group of from 1 to 6 carbon atoms. 
Suitable acylating agents include, by way of example only, acetyl chloride, 
acetic anhydride, benzoyl chloride, p-nitrobenzoyl chloride, 
o-acetylbenzoic acid, cyclohexanecarboxylic acid, 
tri-O-acetyl-fucose(C)-carboxylic acid, azelaic acid, and stearic acid. 
Activated esters of such acids may also be employed. 
When the acylating agent employed is an acyl halide, the acylation reaction 
is typically conducted by contacting compound 9 with about 1.5 to 5 
equivalents of the acyl halide, such as benzoyl chloride, in a suitable 
solvent. A preferred solvent for this reaction is a mixture containing 
about 4 parts of methanol and 1 part of a saturated aqueous solution of 
sodium bicarbonate. The reaction is typically monitored by tlc and 
additional acyl halide may be added periodically until the reaction is 
complete. Generally, the reaction is conducted at a temperature of from 
about 0.degree. to 22.degree. C. for a period of about 1 to about 15 
hours. When benzoyl chloride is employed as the acylating agent, the 
product of the reaction is compound 11;and when p-nitrobenzoyl chloride is 
employed, the product is compound 12. 
Alternatively, the 2-amino group of compound 9 can be acylated using a 
carboxylic acid. This reaction is typically conducted by contacting 
compound 9 with about 1.5 to about 5 equivalents of the carboxylic acid in 
the presence of about 1.5 to about 5 equivalents of a coupling agent. 
Suitable coupling agents include, by way of example, 
1-(3-dimethylaminopropyl)-3-ethylcarbodiimidate hydrochloride and 
dicyclohexyl carbodiimide which provide for the activated ester. The 
reaction is generally conducted in an anhydrous inert solvent, such as 
dichloromethane, at room temperature for about 0.5 to about 24 hours. 
During this period, the reaction is typically monitored by tlc and 
additional amounts of the carboxylic acid and the coupling agent may be 
added periodically until the reaction is complete. When the carboxylic 
acid employed in this reaction is ortho-acetylbenzoic acid, the product is 
compound 13. When the carboxylic acid is cyclohexanecarboxylic acid or 
tri-O-acetyl-fucose(C)-carboxylic acid, the products are compounds 14 and 
19, respectively. 
The 2-amido derivatives of 
8-methoxycarbonyloctyl-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-4- 
O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D 
-glucopyranoside, e.g. compounds 11, 12, 13, 14, and 19, are then 
selectively sulfonated to provide the corresponding 3'-O-sulfo 
derivatives. Selective sulfonation can be achieved by contacting the 
trisaccharide with about 1.0 to about 3 equivalents of a sulfur 
trioxide/pyridine complex in pyridine. Alternatively, sulfur trioxide 
complexes with dimethylformamide, triethylamine, dioxane or mixtures 
thereof may be employed. The conditions for the sulfonation reaction are 
selected to favor substitution only at the 3' position of the galactose 
unit which, in the case of sulfur trioxide in DMF includes reaction at 
from about -30.degree. C. to about -50.degree. C.; whereas for sulfur 
trioxide complexes with pyridine or triethylamine includes reaction 
temperatures of 0.degree. C. to 30.degree. C. In any event, the reaction 
is maintained at this temperature for a period of from about 1 to about 20 
hours to provide for 3'-substitution of the trisaccharide derivative. The 
resulting 3'-O-sulfo derivatives are optionally converted to a salt 
thereof, e.g., compounds 15, 16, 17, 18, and 20, by contact with a 
suitable cation exchange resin. 
Compounds 15, 16, 17, 18 and 20 or similar 2-amido 3'-O-sulfo derivatives 
are then deblocked using conventional deblocking methodology. The 
particular methodology employed is selected based on the blocking groups 
present in the molecule and it is well within the skill of the art to 
select a suitable deblocking methodology. For example, in the case of 
compound 15, deblocking is achieved by hydrogenolysis of the benzyl and 
benzylidene protecting groups which provides for 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-(3-O- 
sulfo-.beta.-D-galactopyranosyl)-2-deoxy-.beta.-D-glucopyranoside, which 
can be converted to a salt by contact with a cation exchange resin. 
Formation of the sodium salt, for example, provides for compound 22. 
Compounds 16, 17 and 18 are similarly deblocked. Compound 20, which 
contains acetyl (Ac) protecting groups on the fuc(C)amido moiety, is. 
first treated with sodium methoxide in methanol to remove the acetyl 
groups to provide for compound 21 and then hydrogenolyzed to provide 
8-methoxycarbonyloctyl-2-fuc(C)amido-3-O-(.alpha.-L-fucopyranosyl)-4-O-(3- 
O-sulfo-.beta.-D-galactopyranosyl)-2-deoxy-.beta.-D-glucopyranoside 26, 
which can be converted to a salt by contact with a cation exchange resin. 
Using methodology similar to that described above for the 2-amido 
derivatives of 
8-methoxycarbonyloctyl-3-O-(.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo-.beta. 
-D-galactopyranosyl)-2-deoxy-.beta.-D-glucopyranoside, the 2-amino 
derivative can be prepared by selectively sulfonating compound 8 using a 
sulfur trioxide-pyridine complex to provide compound 10 and then reducing 
the 2-azido group of compound 10 (while simultaneously removing the benzyl 
blocking groups) by hydrogenating compound 10 in the presence of a 
suitable catalyst, such as 5% palladium on carbon, to provide 
8-methoxycarbonyloctyl-2-amino-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulf 
o-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside, which can be 
converted to a salt by contact with a cation exchange resin. Formation of 
the sodium salt, for example, provides for compound 27. 
B. 2-Amido Lactosamine-OR Derivatives 
FIG. 2 illustrates the synthesis of the 2-p-nitrobenzamido derivative of 
8-methoxycarbonyloctyl-4-O-(.beta.-D-galactopyranosyl)-2-deoxy-.beta.-D-gl 
ucopyranose (e.g., compound 30). Specifically, in FIG. 2, 
8-methoxycarbonyloctyl-2-amino-4-O-(.beta.-D-galactopyranosyl)-2-deoxy-.be 
ta.-D-glucopyranose (28) was prepared by glycosylation of 
2-azido-2-deoxy-3,6,2',3',4',6'-hexa-O-acetyl-.alpha.-D-lactopyranosyl 
bromide (described by Lemieux, et al..sup.22) with 
8-methoxycarbonyloctanol followed by reduction of the azido group with 
H.sub.2 S in pyridine:triethylamine:water (4:1:0.1) and deacetylation. 
This compound is perbenzoylated with p-nitrobenzoyl chloride in pyridine 
to form intermediate 29.The conditions for this reaction are not critical 
and typically the reaction is conducted at a temperature of from about 
-10.degree. C. to about 22.degree. C. for about 5 to about 15 hours or 
until all of the hydroxyl and amino groups present in the oligosaccharide 
glycoside reactant have been acylated. 
The hydroxyl groups of intermediate 29 are then selectively deblocked using 
conventional procedures, preferably using sodium methoxide in methanol, to 
provide 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-4-O-(.beta.-D-galactopyranosyl)- 
2-deoxy-.beta.-D-glucopyranose (30). By employing acyl chlorides of the 
general formula Cl--C(O)R.sup.6 (R.sup.6 is defined as above) in place of 
p-nitrobenzoyl chloride, various 2-amido lactosamine-OR derivatives can be 
prepared. 
C. 4'-Sulfo and 4'-Phospho Lactose-OR Derivatives 
FIG. 3 illustrates the synthesis of the 4-O-sulfo- and 
4-O-phospho-derivatives of 
8-methoxycarbonyloctyl-4-O-(.beta.-D-galactopyranosyl)-.beta.-D-glucopyran 
oside. Specifically, in FIG. 3, 8-methoxycarbonyloctyl lactose (31), 
prepared by the procedures described by Bundle and Banoub.sup.24, is 
converted into a mixture of the 3,4-O-- and 4,6-O-isopropylidene 
derivatives, compounds 32 and 33, respectively, by reaction with 
2,2-dimethoxypropane in the presence of an acidic catalyst, such as 
p-toluenesulfonic acid. The mixture of compounds 32 and 33 is next 
benzoylated with an excess of benzoyl chloride to provide compounds 34 and 
35. The isopropylidine blocking group of compounds 34 and 35 is then 
removed by contacting the mixture with aqueous acetic acid, preferably 80% 
aqueous acetic acid. The resulting diol is generally not isolated but is 
selectively benzoylated with benzoyl chloride at -50.degree. C. to provide 
for compound 36. Compound 36 is then sulfonated using a sulfur 
trioxide/pyridine complex to provide the 4-O-sulfo derivative 37, after 
conversion to its sodium salt. Deblocking of compound 37 using 
conventional procedures, e.g. treatment with sodium methoxide in methanol, 
provides 
8-methoxycarbonyloctyl-4-O-(4-O-sulfo-.beta.-D-galacto-pyranosyl)-.beta.-D 
-glucopyranoside (38), after conversion to its sodium salt. 
Alternatively, intermediate 36 can be phosphorylated with diphenyl 
chlorophosphate and dimethylaminopyridine to give compound 39. Deblocking 
of the phosphate group of compound 39 by hydrogenolysis followed by 
deblocking of the hydroxyl groups using sodium methoxide in methanol 
affords 
8-methoxycarbonyloctyl-4-O-(4-O-phospho-.beta.-D-galactopyranosyl)-.beta.- 
D-glucopyranoside (40), after conversion to its sodium salt. 
D. 3',6'-Disulfo and 3',6'-Diphospho Lewis.sup.C -OR Derivatives 
FIG. 4 illustrates the synthesis of the 3',6'-disulfo- and 
3',6'-diphospho-derivatives of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.beta.-D-galactopyranosyl)-2-deoxy 
-.beta.-D-glucopyranoside, e.g., compounds 43 and 45. As shown in FIG. 4, 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.beta.-D-galactopyranosyl)-2-deoxy 
-4,6-O-benzylidene-.beta.-D-glucopyranoside (41), prepared as described in 
the Examples set forth below, can be selectively disulfonated by treatment 
with about 2 to about 4 equivalents of a sulfur trioxide/pyridine complex 
in pyridine to afford the 3',6'-di-O-sulfo blocked intermediate 42. 
Preferably, this reaction is conducted at a temperature of from about 
0.degree. C. to about 20.degree. C. for a period of about 3 to about 15 
hours. Deblocking of compound 42 using conventional hydrogenolysis 
conditions provides 
8-methoxycarbonyloctyl-2-acetamido-3-O-(3,6-di-O-sulfo-.beta.-D-galactopyr 
anosyl)-2-deoxy-.beta.-D-glucopyranoside (43), after conversion to its 
sodium salt. 
Additionally, the 3' and 6' hydroxyl groups of compound 41 can be 
selectively phosphorylated by treatment with about 2.0 to about 4.0 
equivalents of diphenyl chlorophosphate and about 2.0 to about 4.0 
equivalents of dimethylaminopyridine to provide intermediate 44. This 
reaction is preferably conducted in pyridine at a temperature of from 
about 0.degree. C. to about 20.degree. C. for about 1 to about 5 hours. 
Conventional deblocking of compound 44, e.g. hydrogenolysis, affords 
8-methoxycarbonyloctyl-2-acetamido-3-O-(3,6-di-O-phospho-.beta.-D-galactop 
yranosyl)-2-deoxy-.beta.-D-glucopyranoside (45), after conversion to its 
sodium salt. 
E. 3',4',6'-Trisulfo Lewis.sup.X -OR Derivatives 
FIG. 5 illustrates the synthesis of a 3',4',6'-trisulfo derivative of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-.bet 
a.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside. Specifically, in 
FIG. 5, compound 46, prepared by the procedure described by Srivastava et 
al..sup.23, is selectively tri-O-sulfonated by treatment with about 3.0 to 
about 6.0 equivalents of a sulfur trioxide/pyridine complex in pyridine to 
afford the 3',4',6'-tri-O-sulfo blocked intermediate 47. This reaction is 
preferably conducted at a temperature of from about 0.degree. C. to about 
20.degree. for a period of about 5 to about 15 hours. Deblocking of 
compound 47 using conventional hydrogenolysis conditions provides 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3,4, 
6-tri-O-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside (48), 
after conversion to its sodium salt. 
F. 3'-Sulfo Y-Tetrasaccharide-OR Derivatives 
FIG. 6 illustrates the synthesis of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-2-O-(.alpha.-L-fucopyranosyl)-.beta.-D-galactopyranosyl!-2-deoxy-.bet 
a.-D-glucopyranoside (52) beginning with blocked tetrasaccharide 49. 
Compound 49 can be prepared as set forth in the Examples below. Removal of 
the benzoyl blocking group from compound 49 by treatment with sodium 
methoxide in methanol provides compound 50 having an unblocked hydroxyl 
group in the 3 position of the galactose unit. Sulfonation of this 
hydroxyl group with a sulfur trioxide/pyridine complex provides 
intermediate 51 which is then deblocked under conventional hydrogenolysis 
conditions to afford compound 52, after conversion to its sodium salt. 
G. Chloro, Dichloro, Deoxy and Dideoxy 3'-Sulfo Lewis.sup.X -OR Derivatives 
FIG. 7 illustrates the synthesis of 6'-chloro and 6'-deoxy 
3'-sulfo-Le.sup.x -OR derivatives. As shown in FIG. 7, the unblocked 
hydroxyl group of 1,2,3,4-di-O-isopropylidene-D-galactopyranose (53), 
obtained from Aldrich Chemical Company, Milwaukee, Wis., USA, is first 
converted into a chloro substituent by treatment of compound 53 with an 
inorganic acid halide, such as sulfuryl chloride, in a suitable solvent. 
In a preferred embodiment, compound 53 is contacted with an excess of 
sulfuryl chloride in pyridine. This reaction is typically conducted at a 
temperature in the range from about -40.degree. C. to about 20.degree. C., 
preferably at -40.degree. C., for about 1 to about 15 hours. Subsequent 
hydrolysis of the isopropylidene blocking groups using 90% aqueous 
trifluoroacetic acid followed by acetylation of the resulting unblocked 
hydroxyl groups using conventional procedures, e.g., excess acetic 
anhydride in pyridine, affords intermediate 54. 
Compound 54 is then converted in two steps into 
O-(2,3,4-tri-O-acetyl-6-chloro-6-deoxy-.alpha.-D-glucopyranosyl) 
trichloroacetimidate (55). First, the anomeric acetate group of compound 
54 is selectively removed by reaction with hydrazine acetate. Preferably, 
this reaction is conducted by contacting compound 54 with from about 1.1 
to about 1.5 equivalents of hydrazine acetate (prepared by known 
procedures from hydrazine and acetic anhydride) at a temperature of from 
about 0.degree. C. to about 20.degree. C. for about 5 to about 10 hours. 
Typically, the reaction is conducted in an anhydrous solvent, such as 
dimethylformamide. Treatment of the resulting product with 
trichloroacetonitrile in the presence of an amine, such as 
1,8-diazabicyclo5.4.0!undec-7-ene (DBU), provides compound 55. This 
reaction is typically conducted in an anhydrous inert organic solvent, 
such as dichloromethane, using an excess of trichloroacetonitrile. 
Compound 55 is then coupled with 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (56), prepared 
according to the procedures described by Srivastava et al..sup.23, using 
conventional coupling conditions to provide 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-chloro-6-deoxy-2,3,4-tri-O-acetyl-.beta.-D-galactopyranosy 
l!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (57). The coupling reaction 
is generally conducted by contacting compound 56 with from about 1.1 to 
about 2 equivalents of 
O-(6-chloro-6-deoxy-3,4,6-tri-O-acetyl-.alpha.-D-galactopyranosyl)-trichlo 
roacetimidate (55) and an excess of boron trifluoride etherate relative to 
the galactose imidate. Preferably from about 1.1 to about 2 equivalents of 
boron trifluoride etherate are employed. The reaction is typically 
conducted at from about -30.degree. C. to about 10.degree. C. (preferably 
-10.degree. C.) in a suitable anhydrous organic solvent such as 
dichloromethane or a 1:2 mixture of dichloromethane:ether. 
Compound 57 is then deacetylated using conventional reaction conditions, 
preferably using sodium methoxide in methanol, to provide intermediate 58. 
Sulfonation of compound 58 using conventional procedures, e.g., treatment 
with a sulfur trioxide/pyridine complex, affords the 6'-chloro-3'-O-sulfo 
intermediate 59 which is deblocked using conventional hydrogenolysis 
conditions to provide 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-ch 
loro-6-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-.beta.-D-glucopyranoside 
(60), after conversion to its sodium salt. 
The 6'-deoxy-3'-sulfo-Lewis.sup.X -OR derivative, compound 62, is readily 
prepared from the corresponding blocked 6'-chloro derivative, compound 57, 
by reduction (e.g. de-chlorination) with tributyltin hydride. This 
reaction is typically conducted by contacting compound 57 with about 1.0 
to about 10.0 equivalents of tributyltin hydride, preferably about 10 
equivalents, in the presence of a free radical initiator, such as 
azobisisobutyronitrile (AIBN). The reaction is generally conducted in an 
inert solvent, such as toluene, at a temperature of from about 20.degree. 
C. to about 80.degree. C. for a period of about 1.0 to about 10 hours. 
Reduction of compound 57 under these conditions affords compound 60a. 
Compound 60a is then deacetylated, sulfonated and deblocked using 
conventional techniques to provide 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-de 
oxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-.beta.-D-glucopyranoside (63), 
after conversion to its sodium salt. 
FIG. 8 illustrates the synthesis of 4'-chloro and 4'-deoxy 
3'-sulfo-Lewis.sup.X -OR derivatives. Specifically, in FIG. 8, methyl 
.alpha.-D-glucopyranoside (64) is selectively protected by first forming 
the 4,6-O-benzylidene derivative by reacting compound 64 with benzaldehyde 
dimethylacetal in the presence of an acidic catalyst, such as 
p-toluenesulfonic acid, and then benzoylating the benzylidene intermediate 
using benzoyl bromide in pyridine to provide methyl 
4-6-O-benzylidene-2,3-di-O-benzyl-.alpha.-D-glucopyranoside (65). 
The 4,6-O-benzylidene group of compound 65 is then opened regioselectively 
to provide methyl 6-O-benzyl-2,3-di-O-benzoyl-.alpha.-D-glucopyranoside 
(66), which has an unblocked hydroxyl group at the 4 position of the 
glucose unit. Regioselective opening of the benzylidene group is affected 
by treating compound 65 with at least a molar equivalent, preferably an 
excess, of sodium cyanoborohydride or a similar hydride reducing agent, in 
the presence of an ethereal solution of hydrochloric acid. The reaction is 
typically conducted in a suitable inert solvent, such as tetrahydrofuran 
and is preferably maintained under anhydrous conditions by, for example, 
the inclusion of molecular sieves. A pH indicator, such a methyl orange, 
is generally added to the reaction system and the reaction is generally 
conducted at a pH of about 3 or less. The reaction conditions are not 
critical and the conditions are selected so as to produce compound 66. In 
a preferred embodiment, about 2 to about 20, preferably 5 to 10 
equivalents of sodium cyanoborohydride are employed at a reaction 
temperature of from about -15.degree. C. to about 20.degree. C. 
(preferably 0.degree. C.) for a period of from about 1 to about 7 hours. 
The reaction provides compound 66 as a white solid. 
Reaction of compound 66 with sulfuryl chloride in a suitable solvent, such 
as pyridine, then affords methyl 
6-O-benzyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-.alpha.-D-glucopyranoside 
(67). This reaction is typically conducted at a temperature in the range 
from about -40.degree. to about 20.degree. C., preferably at -40.degree. 
C., using an excess of sulfuryl chloride. Subsequent acetolysis of 
compound 67 using acetic anhydride containing sulfuric acid provides 
acetyl 6-O-acetly-2,3-di-O-benzoyl-4-chloro-4-deoxy-.alpha.-D-galactopyran 
oside (68). 
Compound 68 is next converted in two steps into 
.alpha.-(6-O-acetyl-2,3-di-O-benzoyl4-chloro-4-deoxy-.alpha.-D-galactopyra 
nosyl)-trichloroacetimidate (69). First, the anomeric acetate group of 
compound 69 is selectively removed by reaction with hydrazine acetate. 
This reaction is preferably conducted by contacting compound 69 with from 
about 1.1 to about 1.5 equivalents of hydrazine acetate (prepared by known 
procedures from hydrazine and acetic anhydride) at a temperature of from 
about 0.degree. C. to about 20.degree. C. for about 5 to about 10 hours. 
Typically, the reaction is conducted in an anhydrous solvent, such as 
dimethylformamide. Treatment of the resulting product with 
trichloroacetonitrile in the presence of an amine, such as 
1,8-diazabicyclo5.4.0!undec-7-ene (DBU), provides compound 69. This 
reaction is typically conducted in an anhydrous inert organic solvent, 
such as dichloromethane, using an excess of trichloroacetonitrile. 
Compound 69 is then coupled with 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (56), prepared 
according to the procedures described by Srivastava et al..sup.23, using 
conventional coupling conditions to provide 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-O-acetyl-2, 
3-di-O-benzyl-4-chloro-4-deoxy-.beta.-D-galactopyranosyl!-2-deoxy-6-O-benz 
yl-.beta.-D-glucopyranoside (70). The coupling reaction is generally 
conducted by contacting compound 56 with from about 1.1 to about 2 
equivalents of trichloroacetimidate 69 and an excess of boron trifluoride 
etherate relative to the imidate. Preferably from about 1.1 to about 2 
equivalents of boron trifluoride etherate are employed in this reaction. 
The reaction is typically conducted at from about -30.degree. C. to about 
10.degree. C. (preferably -10.degree. C.) in a suitable anhydrous organic 
solvent such as dichloromethane or a 1:2 mixture of dichloromethane:ether. 
The blocking groups of compound 70 are then manipulated to allow the 
3-hydroxyl group of the galactose unit to be selectively sulfonated. 
Specifically, the acetyl and benzoyl blocking groups of compound 70 are 
first removed using conventional procedures, preferably using sodium 
methoxide in methanol, to provide intermediate 71. The unblocked 
6-hydroxyl group of the galactose unit of compound 71 is then re-blocked 
using a suitable protecting group. Preferably, this hydroxyl group is 
blocked as the tert-butyldimethylsilyl TBDMS) derivative by contacting 
compound 71 with excess tert-butyldimethylsilyl chloride in pyridine. 
Acylation of the remaining hydroxyl groups using conventional procedures, 
e.g., acetic anhydride, provides intermediate 72. The 
tert-butyldimethylsilyl blocking group is then removed by contacting 
compound 72 with tetrabutylammonium fluoride hydrate under conventional 
deblocking conditions to afford intermediate 73. The unblocked hydroxyl 
group of compound 73 is then re-blocked as the benzyl ether by reaction of 
compound 73 with excess benzyl bromide in the presence of silver oxide to 
provide compound 74. Compound 74 is then deacetylated using convention 
conditions, e.g. sodium methoxide in methanol, to afford 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-O-benzyl-4-chloro-4-deoxy-.beta.-D-galactopyranosyl!-2-deo 
xy-6-O-benzyl-.beta.-D-glucopyranoside (75). 
Compound 75 is then sulfonated selectively on the 3-hydroxyl group of the 
galactose unit using a sulfur trioxide/pyridine complex to provide 
compound 76, which is then deblocked using conventional techniques, e.g., 
hydrogenolysis, to afford 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4-ch 
loro-4-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-.beta.-D-glucopyranoside 
(77), after conversion to its sodium salt. 
FIG. 9 illustrates the synthesis of 4',6'-dichloro- and 
4',6'-dideoxy-3'-sulfo-Lewis.sup.X -OR derivatives. Specifically, in FIG. 
9, 3-O-benzyl-D-glucopyranose (78), prepared according to the procedure 
described by Finan, et al..sup.18, is converted into the 4,6-O-benzylidene 
derivative compound 79 using conventional procedures, e.g., reaction with 
benzaldehyde dimethylacetal (dimethoxytoluene) in the presence of an 
acidic catalyst, such as p-toluenesulfonic acid. Acetylation of compound 
79, preferably using acetic anhydride in pyridine, followed by removal of 
the benzylidene blocking group using 80% aqueous acetic acid then provides 
compound 80, having unblocked hydroxyl groups at the 4 and 6 position of 
the glucose unit. 
The unblocked hydroxyl groups of compound 80 are next converted to chloro 
substituents by treatment of compound 80 with a suitable chlorinating 
agent to provide acetyl 
2-O-acetyl-3-O-benzyl-4,6-dichloro-4,6-dideoxy-glucopyranose (81). 
Preferably, compound 80 is contacted with sulfuryl chloride in a suitable 
solvent, such as pyridine. This reaction is typically conducted at a 
temperature in the range from about -40.degree. C. to about 20.degree. C., 
preferably at -40.degree. C., using an excess of sulfuryl chloride. 
The benzyl blocking group of compound 81 is then removed under conventional 
hydrogenolysis conditions and the resulting unblocked 3-hydroxyl group is 
acylated using acetic anhydride in pyridine to provide compound 82. 
Compound 82 is next converted in two steps into 
.alpha.-(2,3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-.alpha.-D-glucopyranosyl 
)-trichloroacetimidate (83). First, the anomeric acetate group of compound 
82 is selectively removed by reaction with hydrazine acetate. This 
reaction is preferably conducted by contacting compound 82 with from about 
1.1 to about 1.5 equivalents of hydrazine acetate (prepared by known 
procedures from hydrazine and acetic anhydride) at a temperature of from 
about 0.degree. C. to about 20.degree. C. for about 5 to about 10 hours. 
Typically, the reaction is conducted in an anhydrous solvent, such as 
dimethylformamide. Treatment of the resulting product with 
trichloroacetonitrile in the presence of an amine, such as 
1,8-diazabicyclo5.4.0!undec-7-ene (DBU), provides compound 83. This 
reaction is typically conducted in an anhydrous inert organic solvent, 
such as dichloromethane, using an excess of trichloroacetonitrile. 
Compound 83 is then coupled with 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (56), prepared 
according to the procedures described by Srivastava et al..sup.23, using 
conventional coupling conditions to provide 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)4-O-2,3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-.beta.-D-galactopyra 
nosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (84). The coupling 
reaction is generally conducted by contacting compound 56 with from about 
1.1 to about 2 equivalents of trichloroacetimidate 83 and an excess of 
boron trifluoride etherate relative to the imidate. Preferably from about 
1.1 to about 2 equivalents of boron trifluoride etherate are employed in 
this reaction. The reaction is typically conducted at from about 
-30.degree. C. to about 10.degree. C. (preferably -10.degree. C.) in a 
suitable anhydrous organic solvent such as dichloromethane or a 1:2 
mixture of dichloromethane:ether. 
Compound 84 is then deacetylated using convention conditions, e.g. sodium 
methoxide in methanol, to afford 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dichloro-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-O-benz 
yl-2-deoxy-.beta.-D-glucopyranoside (85) 
Compound 85 is then sulfonated selectively on the 3-hydroxyl group of the 
galactose unit using a sulfur trioxide/pyridine complex to provide 
compound 86, which is then deblocked using conventional techniques, e.g., 
hydrogenolysis, to afford 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dichloro-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-2-D-glucopyranos 
ide (87), after conversion to its sodium salt. 
The 4',6'-dideoxy-3'-sulfo-Lewis.sup.X -OR derivative, compound 91, can be 
prepared fro m the corresponding blocked 4',6'-dichloro derivative, 
compound 84, by reduction (e.g. de-chlorination) with tributyltin hydride. 
This reaction is typically conducted by contacting compound 84 with about 
1.0 to about 10 equivalents of tributyltin hydride, preferably about 10 
equivalents, in the presence of a free radical initiator, such as AIBN. 
The reaction is generally conducted in an inert solvent, such as toluene, 
at a temperature of from about 20.degree. to about 80.degree. C. for a 
period of about 1 to about 7 hours. Reduction of compound 84 under these 
conditions affords compound 88. 
Compound 88 is then deacetylated, sulfonated and deblocked using 
conventional techniques to provide 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-.beta.-D-glucopyranoside 
(91), after conversion to its sodium salt. 
FIG. 10 illustrates the synthesis of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4-de 
oxy-3-O-Sulfo-.beta.-D-galactopyranosyl-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (95) from the blocked trisaccharide 74 described above. 
Specifically, reduction of the 4'-chloro group of compound 95 to the 
corresponding deoxy derivative is accomplished under conventional 
conditions using tributyltin hydride and azobisisobutyronitrile to provide 
for deoxy compound 92. Deacetylation of the acetyl groups at the 2' and 3' 
positions followed by selective sulfonation with sulfur dioxidedpyridine 
complex leads to the 3'-sulfo derivative, compound 94. Subsequent removal 
of the remaining blocking groups via conventional methods leads to the 
title compound 95. 
H. 1-Azido Compounds and Derivatives Thereof 
FIG. 11 illustrates a reaction scheme for the synthesis of 1-azido-3'-sulfo 
-Lewis.sup.X compounds. Subsequent reduction of the azido group leads to 
the amino group which, in turn, leads to amino derivatives of the formula 
3'-sulfo-Lewis.sup.X -NHR compounds where R is as defined above. 
Specifically, in FIG. 11, the known compound 
3,4,6-triacetyl-2-acetamido-2-deoxy-.alpha.-D-glucopyranoside chloride 100 
is converted to the 
4,6-O-benzylidine-2-acetamido-2-deoxy-D-glucopyranoside azide, compound 
103, by conventional conditions well known in the art and described by 
Unverzagt, et al..sup.35 Specifically, compound 100, as described by 
Srivastava, et al..sup.23, is first converted to the azido derivative by 
reaction with sodium azide in a suitable inert diluent such as 
dichloromethane:water in the presence of the phase transfer catalyst 
tri-n-capryl-methyl ammonium chloride (Aliquat 336) to provide for 
compound 101 which, in turn, is deacetylated by conventional Zemplen 
conditions (NaOMe/MeOH) and then treated under conventional conditions 
with p-methoxybenzyl dimethylacetal to provide for the 
4,6-O-p-methoxybenzylidine derivative 103. 
The 4,6-O-p-methoxybenzylidine derivative, compound 103, is then coupled 
with p-chlorophenyl 
2,3,4-tri-O-p-methoxybenzyl-.beta.-L-thiofucopyranoside, compound 104, 
under conventional coupling conditions to provide for disaccharide 105. 
Compound 104 is prepared in a manner disclosed in Example 1 of Srivastava, 
et al..sup.23 wherein the benzyl groups used in that example are replaced 
with p-methoxybenzyl groups. 
The 4,6-O-benzylidene group of compound 105 is then opened regioselectively 
to provide for compound 106 having an unblocked hydroxyl group at the 
4-position. 
Subsequently, disaccharide 106 is converted to trisaccharide 108 by 
conventional coupling of 
O-(2,3,4,6-tetra-O-acetyl-.alpha.-D-galactopyranosyl)-trichloroacetimidate 
, compound 107, and deacetylation under conventional Zemplin conditions. 
The resulting compound is then selectively protected at the 4,6-positions 
by forming the 4,6-p-methoxybenzylidene derivative by reaction with 
p-methoxybenzaldehyde dimethylacetal in the presence of an acidic 
catalyst, such as pTSA, to provide for compound 109. Selective 
sulfonation, as described above, provides for compound 110 which is 
followed by conventional removal of the protecting groups to provide for 
1-azido-3'-sulfo-Lewis.sup.X compound 111. 
Compound 111 provides for a convenient route for the synthesis of other 
compounds. Specifically, the azido group of compound 111 can be reduced by 
conventional means (e.g., hydrogenation with palladium on carbon) to 
provide for the amino derivative which can then be acetylated, alkylated, 
etc. by conventional means to provide for --NHR derivatives as illustrated 
in Examples 21-27 below. Conventional amine reactions well known in the 
art permit a wide range of --NHR compounds. If desired, the reactions of 
the amino group can be conducted while the reactive hydroxyl groups on the 
trisaccharide are blocked with removable blocking groups to avoid 
unintended reactions at these positions. 
I. Deoxy/Sulfo Compounds 
FIGS. 12 and 16 illustrate the synthesis of Lewis.sup.X -YR compounds 
having a sulfo group on the galactose unit and further having one of the 
hydroxyl groups on the fucose unit being replaced with hydrogen. 
The initial synthetic scheme provided in FIG. 12 illustrates the 
preparation of deoxyfucose compounds which can be incorporated into the 
Lewis.sup.X structures. Specifically, FIG. 12 illustrates the literature 
conversion of methyl 2-O-benzyl-L-fucopyranoside, compound 201, to methyl 
2,3-di-O-benzyl-L-fucopyranoside, compound 202, as reported by 
Deter-Jusynski, et al..sup.36 The free hydroxy in compound 202 is then 
converted to the corresponding (methylthio) thiocarbonyl derivative 203 by 
reaction carbon disulfide and methyl iodide or the corresponding 
imidazolethiocarbonyl derivative 204 by reaction with 
1,1'-thio-carbonyldiimidazole. Reduction of either compound 203 or 204 
provides for the corresponding deoxy derivative 205 which is then 
demethylated under acidic conditions to provide for 
2,3-di-O-benzyl-4-deoxy-L-fucopyranose, compound 206. In turn, compound 
206 is treated with p-chlorothiophenol to provide for the corresponding 
p-chlorophenyl thiofucopyranoside, compound 207, which is now ready for 
coupling to the N-acetylglucosamine unit. 
FIG. 12 illustrates one example of using compound 207 to couple with an 
N-acetylglucosamine unit. Specifically, compound 207 is coupled via 
conventional coupling conditions to disaccharide 208 disclosed in 
International Patent Application Serial No. PCT/US93/04909 to provide for 
fully protected trisaccharide 209. The benzoyl groups of compound 209 are 
differentially removed with sodium hydroxide to provide for trisaccharide 
diol 210. Selective sulfonation, as described above, provides for compound 
211 which is followed by conventional removal of the protecting groups to 
provide for 8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(4-deoxy-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo-. 
beta.-D-galactopyranosyl)-.beta.-D-gluco-pyranoside, compound 212. 
FIG. 16 illustrates another method for the preparation of Lewis.sup.X 
analogues wherein the --YR aglycon is --NHR. Specifically, the synthesis 
of FIG. 16 starts with compound 246 which was prepared in a manner similar 
to compound 103 with the exception that the N-acetyl group is replaced by 
N-phthalimido group and the azido group has been reduced to the amine and 
then converted to the --NHBz group by conventional methods. Compound 246 
is then coupled to compound 207 to provide for disaccharide 247. The 
benzylidene group of disaccharide 247 is then ring opened to provide for 
monohydroxy derivative 248 which is coupled to monosaccharide 249 to 
provide for trisaccharide 250. Removal of the acetyl groups on the 
galactose unit of trisaccharide 250 provides for compound 251 which is 
then converted to the corresponding 4,6-di-O-benzylidene structure 
(compound 252). Conventional removal of the N-phthalimido group provides 
for amine 253 which is then converted to the corresponding N-benzamido 
derivative 254. Selective sulfonation, as described above, provides for 
compound 255 which is followed by conventional removal of the protecting 
groups to provide for compound 256. 
J. 3',4"- and 3',3"-Disulfo-Lewis.sup.X Compounds 
FIG. 13 illustrates the synthesis of 3',4"-disulfo-Lewis.sup.X compounds. 
Specifically, in this figure, known p-chlorophenyl 
.beta.-L-thiofucopyranoside, 213, is converted to the corresponding 
protected 4,6-di-O-benzylidine structure, compound 214, and then the 
hydroxyl group at the 2-position is blocked with a benzyl group to provide 
for compound 215. Removal of the benzylidene group and selective 
benzylation of the 3-hydroxyl group leads to compound 217 which is then 
blocked at the remaining hydroxyl group with a p-methoxybenzyl group to 
provide for compound 218. 
FIG. 13 also illustrates one example of using compound 218 to couple with 
an N-acetylglucosamine unit. Specifically, compound 218 is coupled via 
conventional coupling conditions to disaccharide 208 to provide for fully 
protected trisaccharide 219. The benzoyl groups of compound 219 are 
differentially removed with sodium hydroxide to provide for trisaccharide 
diol 220. Selective sulfonation, as described above, provides for compound 
221 which is followed by conventional removal of the p-methoxybenzyl group 
to provide for diol 222. Again selective sulfonation of compound 222 as 
described above leads to compound 223 followed by removal of the 
protecting groups to provide for 8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(4-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside, compound 224. 
FIG. 14 illustrates the synthesis of 3',3"-disulfo-Lewis.sup.X compounds 
such as 8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside, compound 232. 
Specifically, in this figure, p-chlorophenyl 
2-O-benzyl-.beta.-L-thiofucopyranoside, compound 216 (as described above), 
is converted to the corresponding protected 3-O-p-methoxybenzyl 
derivative, compound 225, and then the hydroxyl group at the 4-position is 
blocked with a benzyl group to provide for compound 226. 
FIG. 14 also illustrates one example of using compound 226 to couple with 
an N-acetylglucosamine unit. Specifically, compound 226 is coupled via 
conventional coupling conditions to disaccharide 208 to provide for fully 
protected trisaccharide 227. The benzoyl groups of compound 227 are 
differentially removed with sodium hydroxide to provide for trisaccharide 
diol 228. Selective sulfonation, as described above, provides for compound 
229. Selective removal of the p-methoxybenzyl protecting group on the 
3-position of the fucose provides for compound 230 which is then 
selectively sulfonated, again as described above, to provide for compound 
231. Conventional removal of the remaining protecting groups provides for 
8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside, compound 232. 
K. 3'-sulfo-3'-methoxy-Lewis.sup.X derivatives 
FIG. 15 illustrates the synthesis of 3'-sulfo-3"methoxy-Lewis.sup.X 
compounds such as 8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-methyl-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulf 
o-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside, compound 245. 
Specifically, in this figure, known methyl 2-O-acetyl-L-fucopyranoside 233 
(Zehavi, et al., J. Org. Chem., 37:13 (1977)) is converted to the 
corresponding protected 3-p-methoxybenzyl derivative, compound 234. The 
acetyl group at the 2 position is removed and the 2,4-hydroxyl groups are 
blocked with benzyl groups to provide for compound 236. Selective removal 
of the p-methoxybenzyl group at the 3-position provides for compound 237 
which is then converted to the (methylthio) thiocarbonyl derivative, 
compound 238. Reduction of this compound provides for the methoxy 
derivative, compound 239 which is then treated under acidic conditions to 
provide for the reducing sugar (240) which is converted under conventional 
conditions to the corresponding p-chlorophenyl thiofucopyranoside 
(compound 241). 
FIG. 15 also illustrates one example of using compound 241 to couple with 
an N-acetylglucosamine unit. Specifically, compound 241 is coupled via 
conventional coupling conditions to disaccharide 208 to provide for fully 
protected trisaccharide 242. The benzoyl groups of compound 242 are 
differentially removed with sodium hydroxide to provide for trisaccharide 
diol 243. Selective sulfonation, as described above, provides for compound 
244 which is followed by conventional removal of the protecting groups to 
provide for 3'-sulfo-3"-methoxy-Lewis.sup.X compounds such as 
8-methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-methyl-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulf 
o-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside, compound 245. 
Additional compounds which can be prepared via similar methods are 
described in Examples 32-52 below the synthesis of which is illustrated in 
FIGS. 17-36. 
Lewis.sup.A Analogues 
The preparation of oligosaccharide glycosides having a 1.fwdarw.3 linkage 
between the galactose unit (or derivatized galactose unit) and the 
N-acetylglucosamine unit (or derivatized N-acetylglucosamine unit) as 
found in formula II above can be prepared by the procedures set forth 
above using appropriately protected N-acetylglucosamine compounds as 
described by, for example, Ippolito et al..sup.32 
Utility 
Without being limited to any theory, it is believed that the 
oligosaccharide glycosides disclosed herein affect the cell mediated 
immune response in a number of ways. Specifically, these compounds can 
inhibit the ability of the immune response to become educated about a 
specific antigen when the compound is administered simultaneously with the 
first exposure of the immune system to the antigen. 
Also, the oligosaccharide glycosides disclosed herein can inhibit the 
secondary immune response to an antigen in a sensitized mammal when 
administered after second or later exposures of the immune system to the 
same antigen. Additionally, the oligosaccharide glycosides disclosed 
herein can induce tolerance to antigens when administered at the time of 
second or later exposures of the immune system to the antigen. 
The suppression of the inflammatory component of the secondary immune 
response by the oligosaccharide glycosides disclosed herein requires 
administering such compounds after initiation of the mammal's secondary 
immune response but at or prior to one-half the period required for 
maximal antigen induced inflammation. This criticality is disclosed in 
allowed U.S. patent application No. 08/081, 214 entitled "Time Dependent 
Administration of Oligosaccharide Glycosides Related to Blood Group 
Determinants Having a Type I or Type II Core Structure in Reducing 
Inflammation in a Sensitized Mammal Arising from Exposure to an Antigen" 
which application is incorporated herein by reference in its entirety. 
In this embodiment, the oligosaccharide glycosides of this invention are 
preferably administered to the patient at least about 0.5 hours after 
antigen exposure, more preferably, at least about 1 to 10 hour after 
antigen exposure, and still more preferably, from about at least about 1 
to 5 hours after antigen exposure. 
Similarly, in cell-mediated inflammatory responses arising from injuries 
(e.g., adult respiratory distress injury (lung injury)), administration of 
an oligosaccharide glycoside of this invention is also conducted after 
initiation of the immune response to this injury but at or prior to 
one-half the period required for maximal inflammation. 
The oligosaccharide glycosides disclosed herein are effective in 
suppressing cell-mediated immune responses including cell-mediated immune 
response to an antigen (e.g., the inflammatory component of a DTH 
response) as well as in suppressing cell-mediated inflammatory responses 
to injury (e.g., lung injury) when administered at a dosage range of from 
about 0.5 mg to about 50 mg/kg of body weight per day, and preferably from 
about 0.5 to about 5 mg/kg of body weight per day. The specific dose 
employed is regulated by the particular cell-mediated immune response 
being treated as well as by the judgment of the attending clinician 
depending upon factors such as the severity of the adverse immune 
response, the age and general condition of the patient, and the like. The 
oligosaccharide glycosides of this invention are generally administered 
parenterally, such as intranasally, intrapulmonarily, transdermally and 
intravenously, although other forms of administration are contemplated. 
In addition to providing suppression of a mammal's secondary immune 
response to an antigen, administration of the oligosaccharide disclosed 
herein also imparts a tolerance to later challenges from the same antigen 
provided that the compound is administered during the critical period 
discussed above. In this regard, re-challenge by the same antigen weeks 
after administration of the oligosaccharide glycoside results in a 
significantly reduced immune response. 
Administration of the oligosaccharide glycosides disclosed herein 
simultaneously with first exposure to an antigen (i.e., a non-sensitized 
mammal) imparts suppression of a cell-mediated immune response to the 
antigen and tolerance to future challenges with that antigen. In this 
regard the term "reducing sensitization" means that the oligosaccharide 
glycoside, when administered to a mammal in an effective amount along with 
a sufficient amount of antigen to induce an immune response, reduces the 
ability of the immune system of the mammal to become educated and thus 
sensitized to the antigen administered at the same time as the 
oligosaccharide glycoside. An "effective amount" of this compound is that 
amount which will reduce sensitization (immunological education) of a 
mammal, including humans, to an antigen administered simultaneously as 
determined by a reduction in a cell-mediated response to the antigen such 
as DTH responses as tested by the footpad challenge test. Preferably the 
reduction in sensitization will be at least about 20% and more preferably 
at least about 30% or more. Generally, the oligosaccharide glycosides 
disclosed herein are effective in reducing sensitization when administered 
at a dosage range of from about 0.5 mg to about 50 mg/kg of body weight 
per day, and preferably from about 0.5 mg to about 5 mg/kg of body weight 
per day. The specific dose employed is regulated by the sensitization 
being treated as well as the judgement of the attending clinician 
depending upon the age and general condition of the patient and the like. 
"Simultaneous" administration of the compound with the antigen with regard 
to inhibiting sensitization means that the compound is administered once 
or continuously throughout a period of time within 3 hours of the 
administration of an antigen, more preferably the compound is administered 
within 1 hour of the antigen. 
The methods of this invention are generally achieved by use of a 
pharmaceutical composition suitable for use in the parenteral 
administration of an effective amount of a oligosaccharide glycoside of 
this invention. These compositions comprise a pharmaceutically inert 
carrier such as water, buffered saline, etc. and an effective amount of a 
oligosaccharide glycoside so as to provide the above-noted dosage of these 
compounds when administered to a patient. Preferably, the pharmaceutical 
compositions comprise from about 1 to 99 weight percent of said inert 
carrier and from 99 to 1 weight percent of the oligosaccharide 
glycoside(s) described herein. It is contemplated that suitable 
pharmaceutical compositions can additionally contain optional components 
such as a preservative, etc. 
It is also contemplated that other suitable pharmaceutical compositions can 
include oral compositions, transdermal compositions or bandages etc., 
which are well known in the art. Therefore, the compositions can be in the 
form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, 
suspensions, emulsions, solutions, syrups, aerosols, ointments, soft and 
hard gelatin capsules, suppositories, sterile injectable solutions and 
sterile packaged powders. It is still further contemplated that the 
oligosaccharide glycoside compound can be incorporated as a part of a 
liposome or a micelle which can then be formulated into a pharmaceutical 
composition. 
It is also contemplated that mixtures of these compounds can be used. 
EXAMPLES 
The following examples are set forth to illustrate the claimed invention 
and are not to be construed as a limitation thereof. 
Examples 1-52 illustrate synthetic procedures for representative 
oligosaccharide glycosides of the present invention. Example A illustrates 
the suppression of antigen-induced inflammation in a mammal by 
administering the oligosaccharide glycoside compounds of Examples 7, 8, 9, 
11, 12 and 13. 
In these examples, the following abbreviations have the following meanings. 
If not defined, any abbreviation used in this application has its 
generally accepted meaning. 
Ac=acetyl 
AIBN=azobisisobutyronitrile 
aq.=aqueous 
Bn=benzyl 
Bz=benzoyl 
CAN=ceric ammonium nitrate 
.degree. C.=degrees Celsius 
d=doublet 
DBU=1,8-diazabicyclo5.4.0!undec-7-ene 
DMF=dimethylformamide 
DTH=delayed type hypersensitivity 
EDTA=ethylene diamine tetraacetic acid 
eq.=equivalents 
g=gram 
Gr=--(CH.sub.2).sub.8 COCH.sub.3 
.sup.1 H-nmr=proton nuclear magnetic resonance 
kg=kilogram 
L=liter 
m=multiplet 
M=molar 
mg=milligrams 
mL=milliliter 
mmol=millimolar 
MP=p-methoxy 
N=normal 
PMB=p-methoxybenzyl 
s=singlet 
THF=tetrahydrofuran 
tlc=thin-layer chromatography 
TR=trityl 
.mu.g=microgram 
.mu.L=microliter 
Example 1 
Synthesis of 
8-Methoxycarbonyloctyl-2-benzamido3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium 
salt (compound 22) 
The synthesis of compound 22 is illustrated in FIG. 1. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-2-deoxy-.beta.-D-glucopyranoside (compound 
1a) 
3,4,6-Tri-O-acetyl-2-azido-2-deoxy-.alpha.-D-glucopyranosyl bromide 
(synthesized according to the procedure described by Paulsen, et 
al..sup.19 and BeMiller, et al..sup.20) (5 g, 12.6 mmol) in 
dichloromethane (5 mL) was added dropwise over a period of 0.5 hours to a 
stirred mixture of 8-methoxy-carbonyloctanol (5.0 g), molecular sieves 4A 
(7.5 g, crushed) and dry silver carbonate (4.5 g) in dichloromethane (5 
mL) at -20.degree. C. The mixture was warmed to -10.degree. C. and stirred 
for 3-4 hours at which time analysis of the mixture by tlc (hexane-ethyl 
acetate; 60:40) indicated that the reaction was complete. The mixture was 
then diluted with dichloromethane and filtered on Celite which had been 
washed twice with water. The solution was then evaporated and the 
resulting crude product was dissolved in pyridine (30 mL) and acetylated 
with acetic anhydride (1.5 mL) at 22.degree. C. for 48 hours. Methanol was 
added to the mixture which was then diluted with dichloromethane, washed 
with water, a solution of sodium bicarbonate, water and brine. The crude 
product was chromatographed on silica gel, eluting with hexane-ethyl 
acetate (75:25), to give 
8-methoxycarbonyloctyl-2-azido-2-deoxy-3,4,6-tri-O-acetyl-.beta.-D-glucopy 
ranoside (compound 1") (5.5 g, 87%). The product was crystallized from 
ethanol. .alpha.!.sub.D.sup.22 -13.2.degree. (C1.0, chloroform); m.p. 
59.degree.-61.degree. C.; .sup.1 H-nmr (CDCl.sub.3) .delta.=5.00(m, 2H, 
H-3 and H-4), 4.39 (d, 1H, J.sub.1,2 7.5 Hz, H-1), 3.45-4.45 m incl. 
OCH.sub.3 (s, 3.67)!, 2.10, 2.05 (2s, 6H, 2 OAc); Anal. Calc. for C.sub.22 
H.sub.35 O.sub.10 N.sub.3 : C, 52.68; H, 7.03; N, 8.38, Found: C, 52.74; 
H, 6.90: N, 8.42. 
A 0.2N solution of sodium methoxide in methanol (0.5 mL) was syringed into 
a flask containing the triacetate compound 1" (5.5 g, 11.0 mmol) in 
methanol (160 mL). After 1 day at 22.degree. C., Dowex(H.sup.+) resin was 
added to the solution and the mixture was stirred, filtered and evaporated 
to give 8-methoxycarbonyloctyl-2-azido-2-deoxy-.beta.-D-glucopyranoside 
(compound 1a) which was used directly in the next step without 
characterization. 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-4,6-O-benzylidene-2-deoxy-.beta.-D-glucopyr 
anoside (compound 1) 
Compound 1a (7.72 g, 20.6 mmol) from step (A) was dissolved in anhydrous 
acetonitrile (80 mL). Benzaldehyde dimethylacetyl (6.2 mL, 41.1 mmol) and 
a catalytic amount of p-toluenesulfonic acid (pTSA) were added and the 
reaction mixture was stirred at room temperature for 5 hours. The reaction 
mixture was then neutralized with triethylamine and evaporated. The 
resulting syrup was chromatographed on silica gel using hexane-ethyl 
acetate (4:1) as the eluent to provide for compound 1 (7.0 g, 73%). 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopyrano 
syl)-4,6-O-benzylidene-2-deoxy-.beta.-D-glucopyranoside (compound 3) 
To a suspension of cupric bromide (12.31 g, 55.12 mmol) and molecular 
sieves (11.0 g) in dry dichloromethane (20 mL) under nitrogen were added 
DMF (8.5 mL, 110.3 mmol) and tetraethylammonium bromide (2.32 g, 11.03 
mmol). After stirring the dark green mixture for approximately 30 minutes 
at room temperature, 
8-methoxycarbonyloctyl-2-azido-4,6-O-benzylidene-2-deoxy-.beta.-D-glucopyr 
anoside (compound 1--5.11 g, 11.03 mmol) was added. After stirring for 5 
minutes, p-chlorophenyl tri-O-benzyl-fucose thioglycoside (compound 
2--11.92 g, 21.2 mmol), was added and the mixture was stirred for 15 hours 
at room temperature. The reaction mixture was then diluted with 
dichloromethane (500 mL) and filtered. The filtrate was washed with 5% 
EDTA solution (5.times.500 mL) and water (2.times.500 mL) and evaporated 
to give a syrup. Chromatography of the syrup on Iatrobeads, eluting with 
hexane-ethyl acetate (5:1), provided compound 3 (5.41 g, 55%). 
Step (D)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopyrano 
syl)-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 4) 
Blocked disaccharide (compound 3--5.0 g, 5.68 mmol), was dissolved in dry 
THF (20 mL) at room temperature. The reaction mixture was cooled and 
molecular sieves were added (500 mg, 3A). Sodium cyanoborohydride (5.27 g, 
83.9 mmol) was then added along with a small amount of methyl orange (a 
few crystals). The reaction mixture was stirred for 15 minutes at 
0.degree. C. and then an etheral solution of hydrochloric acid was added 
until the mixture was acidic (pH.about.3). The reaction mixture was 
stirred for 1 hours at 0.degree. C. at which time all the starting 
material had been completely consumed and converted to the product. The 
reaction mixture was then diluted with dichloromethane (500 mL) and 
triethylamine was added to neutralize (pH.about.6-7) the mixture. The 
resulting mixture was filtered and the precipitate was washed thoroughly 
with dichloromethane (500 mL). The combined filtrates were then washed 
sequentially with a saturated solution of sodium bicarbonate (5.times.1 L) 
and water (2.times.1 L), and then evaporated to provide for compound 4 (3 
g, 60%) as a syrup. 
Step (E)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranosyl!-6-O-benzyl-2-d 
eoxy-.beta.-D-glucopyranoside (compound 6) 
Disaccharide acceptor (compound 4--3.39 g, 3.84 mmol), and imidate donor 
(compound 5--5.6 g, 11.35 mmol) were dissolved in a mixture of diethyl 
ether and dichloromethane (30 mL, 2:1) and stirred at -10.degree. C. for 
15 minutes. Boron trifluoride etherate (2.33 mL, 18.92 mmol) was added and 
the reaction mixture was stirred under nitrogen for 15 hours at 0.degree. 
C. The reaction mixture was then diluted with dichloromethane (500 mL), 
filtered and washed successively with a saturated solution of sodium 
bicarbonate (2.times.500 mL) and water (2.times.500 mL). Evaporation of 
the solvent gave a syrup which was purified by chromatography on 
Iatrobeads, eluting with hexane-ethyl acetate, to provide for compound 6 
(3.5 g, 75%). 
Step (F)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-3-O-(2,3,4-tri-O-benzyI-.alpha.-L-fucopyran 
osyl)-4-O-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyra 
noside (compound 7) 
Trisaccharide 6 (4.81 g, 3.97 mmol) was dissolved in methanol (50 mL) and a 
catalytic amount of sodium methoxide (0.5M solution) in methanol was 
added. The reaction mixture was stirred for 5 hours at room temperature 
and then neutralized with IR-120(H.sup.+) ion exchange resin and filtered. 
The filtrate was then evaporated and the resulting residue was purified by 
chromatography on silica gel, eluting with hexane-ethyl acetate (1:4), to 
provide tetrol trisaccharide 7 (4.0 g, 96.5 %). 
Step (G)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylldene-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy- 
.beta.-D-glucopyranoside (compound 8) 
To a solution of tetrol trisaccharide 7 (1.81 g, 1.73 mmol) dissolved in 
anhydrous acetonitrile (20.0 mL) was added benzaldehyde dimethylacetate 
(520.3 .mu.L, 3.47 mmol) and a catalytic amount of p-toluenesulfonic acid. 
The reaction mixture, which had a pH of .about.3, was monitored by tlc. 
After stirring the reaction mixture for 5 hours at room temperature, tlc 
indicated that the starting material had been completely consumed and a 
new spot having a higher Rf was observed. The reaction mixture was then 
neutralized with triethylamine (1.0 mL) and evaporated. The resulting 
residue was chromatographed on silica gel, eluting with hexane-ethyl 
acetate (1:2), to provide diol 8 (1.5 g, 77%). 
Step (H)--Preparation of 
8-Methoxycarbonyloctyl-2-amino-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy- 
.beta.-D-glucopyranoside (compound 9) 
A solution of diol 8 (1.5 g, 1.32 mmol) in a mixture of pyridine, 
triethylamine and water (2:0.5:0.05, 20 mL) was saturated with a stream of 
hydrogen sulfide, initially at 0.degree. C. for 2 hours and then at room 
temperature for 15 hours. After stirring the reaction mixture for 15 hours 
at room temperature, the solvents were evaporated and then co-evaporated 
with toluene under high vacuum to remove pyridine. The resulting material 
was chromatographed on silica gel, eluting with hexane-ethyl acetate (1:2) 
and (1:4), to provide compound 9 (1.4 g, 96%). 
Step (I)--Preparation of 
8-Methoxycarbonyloctyl-2-benzamido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopy 
ranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deo 
xy-.beta.-D-glucopyranoside (compound 11). 
To a solution of amino sugar 9 (5.59 g, 5.05 mmol) in methanol (50 mL) was 
added a saturated sodium hydrogen carbonate solution (100 mL). The 
reaction mixture was then stirred at 0.degree. C. for 10 minutes. Benzoyl 
chloride (1.15 mL, 9.94 mmol) was then added and stirring was continued 
for 1 hour at room temperature by which time the starting material had 
been completely consumed. The reaction mixture was then diluted with 
dichloromethane (500 mL), filtered and evaporated. The residue was 
chromatographed on an Iatrobeads column, eluting with hexane-ethyl acetate 
(2:1), to provide compound 11 (5.0 g, 82%). 
Step (J)--Preparation of 
8-Methoxycarbonyloctyl-2-benzamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-b 
enzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 15) 
To a solution of diol 11 (370 mg, 0.31 mmol) in pyridine (5.0 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (97.3 mg, 0.62 mmol) and 
the resulting reaction mixture was allowed to warm at room temperature. 
After stirring for 1 hour, tlc indicated that the starting material was 
not completely consumed so additional SO.sub.3 -pyridine complex (1 eq) 
was added and stirring was continued for 2 hours. At this time, tlc 
indicated that there was no remaining starting material. The mixture was 
then quenched with methanol (5.0 mL) and evaporated to dryness. The 
residue was chromatographed on Iatrobeads, eluting with 
dichloromethane-methanol-pyridine (95:5:0.5), to provided compound 15 (310 
mg, 76%). 
Step (K)--Preparation of 
8-Methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium 
salt (compound 22). 
A mixture of compound 15 (330 mg, 0.25 mmol) and 5 % palladium on carbon 
(330 mg) in methanol (5.0 mL) was stirred under one atmosphere of hydrogen 
for 5 hours. The mixture was then filtered through a pad of Celite to 
remove the catalyst and the Catalyst/Celite was washed with methanol (100 
mL). The filtrate and washings were combined and evaporated after adding a 
trace of pyridine (5.0 mL). The resulting product was chromatographed on 
Iatrobeads, eluting with isopropanol-water-ammonia (7:15:0.5), to provide 
compound 22 (150 mg, 70%) after conversion to the sodium salt by passage 
through Dowex-50-x-8-(Na.sup.+) resin. 
Example 2 
Synthesis of 
8-Methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-(.alpha.-L-fucopyranosyl)-4- 
O-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 23) 
The synthesis of compound 23 is illustrated in FIG. 1. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-(2,3,4-tri-O-benzyl-.alpha.- 
L-fucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O-benz 
yl-2-deoxy-.beta.-D-glucopyranoside (compound 12) 
To a solution of amino sugar 9 (310 mg, 0.28 mmol) (prepared as described 
in Example 1) in methanol (4.0 mL) was added a saturated solution of 
sodium bicarbonate (1.0 mL). The reaction mixture was stirred for 15 
minutes at room temperature, cooled to 0.degree. C., and then 
p-nitrobenzoyl chloride (104 mg, 0.56 mmol) was added. After 15 minutes, 
tlc indicated that 75% of starting material had been consumed. Additional 
4-nitrobenzoyl chloride (150.0 mg) was added and the reaction mixture was 
stirred at room temperature for 15 hours. At this time, tlc indicated the 
reaction was essentially complete. The mixture was then diluted with 
dichloromethane (100 mL) and washed with a saturated solution of sodium 
bicarbonate (2.times.100 mL) and water (2.times.100 mL). Evaporation of 
the solvent gave a residue which was purified by chromatography on 
Iatrobeads, eluting with hexane-ethyl acetate (1:2), to provide compound 
12 (250 mg, 71%). 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-p-nitro-benzamido-3-O-(2,3,4-tri-O-benzyl-.alpha. 
-L-fucopyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosy 
l!-2-deoxy-6-O-benzyl-.beta.-D-glucopyranoside sodium salt (compound 16) 
To a solution of diol 12 (277 mg, 0.22 mmol) in pyridine (3.0 mmol) at 
0.degree. C. was added SO.sub.3 -pyridine complex (52.7 mg, 0.33 mmol). 
The reaction mixture was stirred for 0.5 hours at 0.degree. C. and then 
for 2 hours at room temperature. An additional amount of SO.sub.3 
-pyridine complex (1 eq) was then added and stirring was continued for 2 
hours at room temperature. The excess reagent was destroyed by adding 
methanol and the mixture was evaporated. The resulting syrup was purified 
by chromatography on Iatrobeads, eluting with 
dichloromethane-methanol-pyridine (95:5:0.5), to provide compound 16 (250 
mg, 84%). 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-(.alpha.-L-fucopyranosyl)-4- 
O-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 23) 
Compound 16 (350 mg, 0.26 mmol) was hydrogenolyzed in the presence of 5% 
palladium on carbon (350 mg) using the procedure described in Example 1, 
Step K for compound 15. Conversion of the resulting product to its sodium 
salt by passage through Dowex-50-x-8 (Na.sup.+) resin provided compound 23 
(180 mg, 76%) after lyophilization. 
Example 3 
Synthesis of 
8-Methoxycarbonyloctyl-2-ortho-acetyl-benzamido-3-O-(.alpha.-L-fucopyranos 
yl)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranos 
ide sodium salt (compound 24) 
The synthesis of compound 24 is illustrated in FIG. 1. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-ortho-acetylbenzamido-3-O-(2,3,4-tri-O-benzyl-.al 
pha.-L-fucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O 
-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 13) 
To a solution of amino sugar 9 (270 mg, 0.24 mmol) (prepared as described 
in Example 1) in dichloromethane (5.0 mL) at room temperature was added 
2-o-acetylbenzoic acid (80 mg, 0.49 mmol) and 
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (145 mg, 0.49 
mmol). The reaction mixture was then stirred at room temperature 
overnight. Tlc indicated that some starting material remained so 1 
additional equivalent of both reagents were added and stirring was 
continued for 15 hours. The reaction mixture was then diluted with 
dichloromethane, washed with water, dried over anhydrous sodium sulfate 
and evaporated. Chromatography of the residue on Iatrobeads, eluting with 
toluene-ethanol (95:5), provided compound 13 (250 mg, 83%). 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-ortho-acetylbenzamido-3-O-(2,3,4-tri-O-benzyl-.al 
pha.-L-fucopyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyra 
nosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 
18). 
To a solution of diol 13 (300 mg, 0.24 mmol) in pyridine (3.0 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (75.2 mg, 0.47 mmol). 
The reaction mixture was stirred at 0.degree. C. for 1 hour and then at 
room temperature for 2 hours. Additional SO.sub.3 -pyridine complex (0.5 
eq) was then added and stirring was continued for an additional 3 hours at 
room temperature. The excess SO.sub.3 -pyridine complex was destroyed by 
adding methanol and the solution was evaporated. The residue was 
chromatographed on a silica gel, eluting with 
dichloromethane-methanol-pyridine (95:5:05), to provide compound 18 (250 
mg, 77%) after conversion to a sodium salt by passage through Dowex 50-X-8 
(Na.sup.+) resin. 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-ortho-acetylbenzamido-3-O-(.alpha.-L-fucopyranosy 
l)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosi 
de sodium salt (compound 24) 
Compound 18 (300 mg, 0.22 mmol) was hydrogenolyzed in the presence of 5% 
palladium on carbon (300 mg) using the procedure described in Example 1, 
Step K for compound 15. Conversion of the resulting product to its sodium 
salt by passage through Dowex-50-x-8 (Na.sup.+) resin provided compound 24 
(150 mg, 75%) after lyophilization. 
Example 4 
Synthesis of 
8-Methoxycarbonyloctyl-2-cyclohexamido-3-O-(.alpha.-L-fucopyranosyl)-4-O- 
3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 25) 
The synthesis of compound 25 is illustrated in FIG. 1. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-cyclohexamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-f 
ucopyranosyl)-4-O-4,6-O-benzylldene-.beta.-D-galactopyranosyl!-6-O-benzyl- 
2-deoxy-.beta.-D-glucopyranoside (compound 14) 
To a solution of amino sugar 9 (270 mg, 0.24 mmol) (prepared as described 
in Example 1) in dichloromethane (50 mL) at room temperature was added 
cyclohexanecarboxylic acid (31.27 mg, 0.49 mmol) and 
1-(3-dimethylaminopropyl)-3-ethylcarbodiimidate hydrochloride (145 mg, 
0.49 mmol). The reaction mixture was stirred for 15 hours at room 
temperature and then an additional 0.49 mmol amount of each reagent was 
added and stirring was continued overnight. The mixture was then diluted 
with dichloromethane (100 mL) and the dichloromethane layer washed with 
water (2.times.100 mL), dried and evaporated. The residue was 
chromatographed on Iatrobeads, eluting with dichloromethane-methanol 
(97:3), to provided compound 14 (230 mg, 79%). 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-cyclohexamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-f 
ucopyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6 
-O-benzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 17) 
To a solution of compound 14 (231.5 mg, 0.19 mmol) in dry pyridine (3.0 mL) 
at 0.degree. C. was added SO.sub.3 -pyridine complex (45.5 mg, 0.29 mmol). 
The solution was allowed to warm at room temperature by which time tlc 
indicated that all the starting material had been consumed. The excess 
SO.sub.3 -pyridine complex was destroyed by adding methanol (1 mL) and the 
reaction mixture was evaporated. The resulting residue was chromatographed 
on an Iatrobeads column eluting with dichloromethane-methanol-pyridine 
(95:5:0.5), to provide compound 17 (225 mg, 90%) after conversion to a 
sodium salt by passage through Dowex 50-X-8 (Na.sup.+) resin. 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-cyclohexamido-3-O-(.alpha.-L-fucopyranosyl)-4-O- 
3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 25) 
Compound 17 (216 mg, 0.16 mmol) was hydrogenolyzed in the presence of 5% 
palladium on carbon (200 mg) using the procedure described in Example 1, 
Step K for compound 15. Conversion of the resulting product to its sodium 
salt by passage through Dowex-50-x-8 (Na.sup.+) resin provided compound 25 
(120 mg, 86%) after lyophilization. 
Example 5 
Synthesis of 
8-Methoxycarbonyloctyl-2-fuc(C)amido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3- 
O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium 
salt (compound 26) 
The synthesis of compound 26 is illustrated in FIG. 1. 
Step (A)--Preparation of C-Fucoside 
To a stirred mixture of 
1-allyl-1-deoxy-2,3,4-tri-O-acetyl-.alpha.-L-fucopyranose (10 g, 31.9 
mmols) (prepared as described by Luengo, et al..sup.33) in a solvent 
mixture of acetonitrile:carbon tetrachloride:water (80 mL:80 mL:120 mL)), 
was added 28.0 g (131.2 mmole) of sodium periodate followed by ruthenium 
trichloride hydrate (145 mg) in the manner described by Carlsen et 
al..sup.34. The reaction became exothermic after 10 minutes and was 
stirred overnight at room temperature. The mixture was diluted with water 
(300 mL) and extracted with dichloromethane (2.times.300 mL). The combined 
organic layer was washed with water (100 mL) and concentrated. The 
residual oil was dissolved in ethyl acetate (200 mL) and extracted with 
saturated sodium bicarbonate (30 mL). The organic layer was washed again 
with water (20 mL) which was combined with the sodium bicarbonate solution 
extracts. This combined aqueous extract was acidified with 6N hydrochloric 
acid solution to pH 1 and extracted with dichloromethane (2.times.200 mL). 
The combined organic extracts were washed with water (100 mL), followed by 
saturated sodium chloride solution, dried over sodium sulfate, filtered 
and concentrated to give 6.9 g (20.8 mmole, 65%) of 
(1-deoxy-2,3,4-tri-O-acetyl-.alpha.-L-fucopyranoside) acetic acid. 
Deacetylation of this compound provides for fucose(C)carboxylic acid. 
If desired, the fucose(C)carboxylic acid can be converted to its 
NHS-C-fucoside via conventional methods. For example, 
(1-deoxy-2,3,4-tri-O-acetyl-.alpha.-L-fucopyranoside) acetic acid (1.97 g, 
6.16 mmol) was dissolved in dichloromethane (25 mL) and 
N-hydroxysuccinimide (NHS, 1.0 g, 8.69 mmol) was added to the solution, 
and the solution was warmed to dissolve the NHS. Dicyclohexylcarbodiimide 
(DCC, 1.41 g, 6.83 mmol) was dissolved in dichloromethane (5 mL) and added 
to the reaction mixture with stirring. After 5 hours, the reaction mixture 
was cooled to 4.degree. C., filtered and evaporated. The syrupy residue 
was taken up in ethyl acetate (50 mL), filtered and washed with water 
(2.times.25 mL). The ethyl acetate layer was dried over anhydrous sodium 
sulfate, filtered and evaporated. After drying under high vacuum, 2.5 g 
(94%) of an amorphous white solid 
(1-deoxy-2,3,4-tri-O-acetyl-.alpha.-L-fucopyranosyl) acetic acid 
N-hydroxysuccinimide ester was obtained. 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-(2,3,4-tri-O-acetyl-fuc-(C)-amido)-3-O-(2,3,4-tri 
-O-benzyl-.alpha.-L-fucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactop 
yranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 19) 
To a solution of amino sugar 9 (270 mg, 0.24 mmol) (prepared as described 
in Example 1) in dichloromethane (2.0 mL) at room temperature was added 
fucose(C)carboxylic acid (443 mg) and 
1-(3-dimethylaminopropyl)-3-ethylcarbodiimidate hydrochloride (443 mg). 
The reaction mixture was stirred for 15 hours at room temperature and then 
diluted with dichloromethane (100 mL). The organic layer was washed with 
water (3.times.100 mL), dried over anhydrous sodium sulfate and 
evaporated. The residue was then chromatographed on Iatrobeads, eluting 
with dichloromethane-methanol (95:5), to provided compound 19 (286 mg, 
84%). 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-(2,3,4-tri-O-acetyl-fuc(C)amido)-3-O-(2,3,4-tri-O 
-benzyl-.alpha.-L-fucopyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D- 
galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt 
(compound 20) 
To a solution of diol 19 (286 mg, 0.2 mmol) in anhydrous dichloromethane 
(3.0 mL) at 0.degree. C. was added SO.sub.3 -pyridine complex (2 eq). The 
reaction mnixture was allowed to warm to room temperature and was stirred 
for 3 hours. The excess SO.sub.3 -pyridine complex was destroyed by adding 
methanol (1.0 mL) and the solution was then evaporated. The resulting 
residue was chromatographed on an Iatrobead column, eluting with 
dichloromethane-methanol-pyridine (95:5:0.5), to provided compound 20 (250 
mg, 82%) after conversion to the sodium salt by passage through Dowex 
50-X-8 (Na.sup.+) resin. 
Step (D)--Preparation of 
8-Methoxycarbonyloctyl-2-fuc(C)amido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fuc 
opyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O 
-benzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 21) 
To a solution of compound 20 (240 mg, 0.158 mmol) in methanol (5.0 mL) was 
added sodium methoxide in methanol (0.5M solution). The resulting solution 
was stirred for 5 hours at room temperature and then neutralized with 
IR-120(H.sup.+) ion exchange resin, filtered (the filtered residue was 
washed with methanol) and evaporated. The resulting residue was 
chromatographed on Iatrobeads, eluting with 
dichloromethane-methanol-pyridine (95:5:0.5), to provide compound 21 (180 
mg, 82%) after conversion to the sodium salt by passage through Dowex 
50-X-8 (Na.sup.+) resin. 
Step (E)--Preparation of 
8-Methoxycarbonyloctyl-2-fuc(C)amido-3-O-(.alpha.-L-fucopyranosyol)-4-O-3 
-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium 
salt (compound 26) 
Compound 21 (250 mg, 0.179 mmol) was hydrogenolyzed in the presence of 5% 
palladium on carbon (250 mg) using the procedure described in Example 1, 
Step K for compound 15. Conversion of the resulting product to its sodium 
salt by passage through Dowex-50-x-8 (Na.sup.+) resin provided compound 26 
(150 mg, 88%) after lyophilization. 
Example 6 
Synthesis of 
8-Methoxycarbonyloctyl-2-amino-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulf 
o-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium salt 
(27) 
The synthesis of compound 27 is illustrated in FIG. 1. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-azido-3-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-benzy 
l-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 10) 
To a solution of diol 8 (5.0 g, 4.42 mmol)(prepared as described in Example 
1) dissolved in pyridine (50.0 mL) at 0.degree. C. was added SO.sub.3 
-pyridine complex (1.05 g, 6.62 mmol). The reaction mixture was stirred 
for 0.5 hours at 0.degree. C. and then for 1 hour at room temperature. The 
reaction was not complete, so additional SO.sub.3 -pyridine complex (500 
mg) was added and stirrng was continued for an additional 2 hours. The 
reaction mixture was then quenched with methanol and the solvent 
evaporated. Chromatography of the resulting syrup using 
dichloromethane-methanol-pyridine (95:5:0.5) as eluent provided compound 
10 (4.0 g, 73 % ) after sodium ion exchange column. 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-amino-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulf 
o-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium salt 
(compound 27) 
Compound 10 (250 mg, 0.2 mmol) was dissolved in methanol (5.0 mL) 
containing 0.1% HCl in MeOH and 5 % palladium on carbon (250 mg) was 
added. The reaction mixture was stirred for 6 hours at room temperature 
and then the catalyst was removed by filtration. Pyridine was added and 
the solution was evaporated. Conversion of the resulting product into its 
sodium salt by passage through Dowex-50-x-8 (Na.sup.+) resin provided 
compound 27 (120 mg, 78%) as a white powder after lyophilization. 
Example 7 
Synthesis of 
8-Methoxycarbonyloctyl-2-p-nitrobenzamido-4O-(.beta.-D-galactopyranosyl)-2 
-deoxy-.beta.-D-glucopyranose (30) 
The synthesis of compound 30 is illustrated in FIG. 2. 
8-methoxycarbonyloctyl-2-amino-4-O-(.beta.-D-galactopyranosyl)-2-deoxy-.bet 
a.-D-glucopyranose (28) (250 mg, 0.489 mmol), prepared by glycosylation of 
2-azido-2-deoxy-3,6,2',3',4',6'-hexa-O-acetyl-.alpha.-D-lactopyranosyl 
bromide.sup.22 with 8-methoxycarbonyloctanol followed by reduction with 
H.sub.2 S in pyridine:triethylamine:water (4:1:0.1) and deacetylation, was 
added to pyridine (5 mL) followed by addition of p-nitrobenzoyl chloride 
(2.5 g). The reaction mixture was stirred for 15 hours at room temperature 
and then excess p-nitrobenzoyl chloride was destroyed by adding methanol 
(5 mL). The mixture was evaporated and the residue was diluted with 
dichloromethane (100 mL). This solution was washed with a 5% solution of 
hydrochloric acid (2.times.100 mL), aqueous sodium bicarbonate 
(2.times.100 mL) and water (2.times.100 mL), then dried over sodium 
sulfate, filtered and evaporated to dryness to give compound 29 which was 
used without further purification. 
Compound 29 was debenzoylated by dissolving the compound in sodium 
methoxide (0.5M solution) in methanol and stirring the resulting mixture 
for 15 hours at room temperature. The reaction mixture was then 
neutralized by adding IR-120(H+) ion exchange resin and the resin was 
removed by filtration. The filtrate was evaporated to dryness and the 
resulting residue was purified by chromatography on Iatrobeads, eluting 
with dichloromethane-methanol-water (80:20:2), to provide compound 30 (210 
mg, 68% based on compound 28). 
Example 8 
Synthesis of 
8-methoxycarbonyloctyl-4-O-(4-O-sulfo-.beta.-D-galactopyranosyl)-.beta.-D- 
glucopyranoside sodium salt (compound 38) 
The synthesis of compound 38 is illustrated in FIG. 3. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-4-O-(2,3,6-tri-O-benzoyl-.beta.-D-galactopyranosyl) 
-2,3,6-tri-O-benzoyl-.beta.-D-glucopyranoside (compound 36) 
To a solution of 8-methoxycarbonyloctyl lactopyranoside (compound 31) (9.5 
g, 18.5 mmol) (prepared as described in Banoub, et al..sup.24) in 
acetonitrile (100 mL) at room temperature was added 2,2-dimethoxypropane 
(4.56 mL, 37 mmol) and p-toluenesulfonic acid (95 mg). After stirring for 
3 hours at room temperature, the reaction mixture was neutralized by 
adding trimethylamine (1.0 mL). The mixture was then evaporated to dryness 
and the residue filtered through silica gel using dichloromethane-methanol 
(80:20) to provide the 3,4- and 4,6-O-isopropylidene derivatives 32 and 
33. 
The mixture of compounds 32 and 33 prepared above was dissolved in pyridine 
and dichloromethane (50 mL) (1:9) and cooled to 0.degree. C. Benzoyl 
chloride (10.0 mL) was added dropwise at 0.degree. C. and resulting 
mixture was stirred for 15 hours at room temperature. The excess benzoyl 
chloride was then neutralized by adding methanol (5.0 mL) and the reaction 
mixture evaporated. The residue was diluted with dichloromethane (250 mL), 
washed with 5% aq. hydrochloric acid (2.times.250 mL), saturated sodium 
bicarbonate (2.times.250 mL) and water (2.times.250 mL), dried over 
anhydrous sodium sulfate, filtered and evaporated. The resulting residue 
was chromatographed on silica gel, eluting with dichloromethane-methanol 
(98:2) and (95:5), to provide a mixture of compounds 34 and 35 (14.5 g). 
The mixture of compounds 34 and 35 prepared above was dissolved in 80% 
aqueous acetic acid and this solution was stirred at room temperature for 
15 hours. The mixture was then evaporated and co-evaporated with toluene 
to dryness. The resulting residue was then benzoylated by adding benzoyl 
chloride (1.3 eq) in a mixture of dichloromethane-pyridine (9:1) at 
-50.degree. C. Standard work-up procedures gave a residue (one major spot 
by tlc) which was chromatographed on silica gel, eluting with hexane-ethyl 
acetate (2:1), to provide compound 36 (11.5 g). 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-4-O-(4-O-sulfo-2,3,6-tri-O-benzoyl-.beta.-D-galacto 
pyranosyl)-2,3,6-tri-O-benzoyl-.beta.-D-glucopyranoside sodium salt 
(compound 37) 
To a solution of compound 36 (50 mg, 0.44 mmol) in pyridine (2.0 mL) was 
added SO.sub.3 -pyridine complex (14 mg, 0.88 mmol). The resulting mixture 
was stirred for 1 hour at room temperature. Additional SO.sub.3 -pyridine 
complex (36 mg) was then added and stirring was continued for 3 hours. The 
reaction mixture was quenched with methanol (1.0 mL) and evaporated to 
dryness. The residue was chromatographed on silica gel, eluting with 
dichloromethane-methanol-pyridine (95:5:0.5), to provide compound 37 (50 
mg, 92%) after conversion to sodium salt by passage through Dowex-50-x-8 
(Na.sup.+) resin. 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-4-O-(4-O-sulfo-.beta.-D-galactopyranosyl)-.beta.-D- 
glucopyranoside sodium salt (compound 38) 
To a solution of compound 37 (50 mg, 0.04 mmol) in methanol (5.0 mL) was 
added a 0.5 molar solution of sodium methoxide in methanol. The resulting 
solution was stirred at room temperature for 15 hours. The mixture was 
then neutralized by adding IR-120 (H.sup.+) resin, filtered and evaporated 
to dryness. The residue was chromatographed on silica gel, eluting with 
dichloromethane-methanol-water-pyridine (80:20:2:2), to provide compound 
38 (20.0 mg, 81 %) after sodium exchange and lyophilization. 
Example 9 
Synthesis of 
8-Methoxycarbonyloctyl-4-O-(4-O-phospho-.beta.-D-galactopyranosyl)-.beta.- 
D-glucopyranoside disodium salt (compound 40) 
The synthesis of compound 40 is illustrated in FIG. 3. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-4-O-(4-O-phospho-2,3,6-tri-O-benzoyl-.beta.-D-galac 
topyranosyl)-2,3,6-tri-O-benzoyl-.beta.-D-glucopyranoside disodium salt 
(compound 39) 
To a solution of compound 36 (1.0 g, 0.88 mmol) in dry pyridine (5.0 mL) at 
0.degree. C. was added dimethylaminopyridine (161 mg, 1.32 mmol) and 
diphenylphosphorochloride (365 .mu.L, 1.76 mmol). The resulting mixture 
was stirred at 0.degree. C. for 1 hour and then at room temperature for 5 
hours by which time tic showed complete consumption of the starting 
material. The mixture was then diluted with dichloromethane (250 mL), 
washed with cold 5% HCl solution (2.times.250 mL), saturated sodium 
bicarbonate solution (2.times.250 mL) and water (2.times.250 mL), and 
evaporated to dryness. The residue was chromatographed on a silica gel, 
eluting with dichloromethane-methanol (95:5), to provided compound 39 (1.0 
g, 83%). 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-4-O-(4-O-phospho-.beta.-D-galactopyranosyl)-.beta.- 
D-glucopyranoside disodium salt (compound 40) 
A solution of compound 39 (750 mg, 0.55 mmol) in methanol (20.0 mL) 
containing PtO.sub.2 on carbon (750 mg) was hydrogenolysed for 15 hours at 
1 atmosphere of hydrogen. The catalyst was filtered and the solution was 
evaporated after adding pyridine (1.0 mL). The residue was saponified by 
reacting with sodium methoxide (0.5 molar solution) in methanol using 
standard conditions and workup. The debenzoylated product was 
chromatographed on an Iatrobeads column, eluting with 
isopropanol-water-ammonia (7:3:1), to provide compound 40 (300 mg, 86%). 
Example 10 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(3,6-di-O-sulfo-.beta.-D-galactopyr 
anosyl)-2-deoxy-.beta.-D-glucopyranoside disodium salt (compound 43) 
The synthesis of compound 43 is illustrated in FIG. 4. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.beta.-D-galactopyranosyl)-2-deoxy 
-4,6-O-benzylidene-.beta.-D-glucopyranoside (compound 41) 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.beta.-D-galactopyranosyl)-2-deoxy- 
4,6-O-benzylidene-.beta.-D-glucopyranoside, compound 41, was prepared by 
coupling with thiobenzyl-2,3,4,6-tetraacetyl-.beta.-D-galactopyranoside 
(reported by Ippolito et al..sup.32) with the 
8-methoxycarbonyloctyl-2-acetamido-4,6-O-benzylidene-2-deoxy-.beta.-D-gluc 
opyranoside (also reported by Ippolito et al..sup.32). Specifically, 1.5 
equivalents of n-iodosuccinimide, 1 equivalent of 
8-methoxycarbonyloctyl-2-acetamido-4,6-O-benzylidene-2-deoxy-.beta.-D-gluc 
opyranoside (glycosyl donor), 1.5 equivalents of 
thiobenzyl-2,3,4,6-tetraacetyl-.beta.-D-galactopyranoside (glycosyl 
acceptor) and molecular sieves were first combined in dichloromethane and 
then stirring the mixture for 0.5 hours at -20.degree. C. Then, 1 to 1.5 
equivalents of trifluoromethane sulfonic acid was added and the reaction 
mixture stirred for 3 hours at -20.degree. C. The reaction mixture was 
quenched by adding triethylamine until neutral pH was reached. The 
reaction solution was filtered, washed with sodium bicarbonate and water. 
The organic layer was dried over sodium sulfate and the solvent evaporated 
to provide for the fully protected 
8-methoxycarbonyloctyl-3-O-(2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranos 
yl)-2-acetamido-4,6-O-benzylidene-2-deoxy-.beta.-D-glucopyranoside which 
was then subjected to Zemplen conditions (sodium methoxide/methanol) to 
provide for 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.beta.-D-galactopyranosyl)-2-deoxy 
-4,6-O-benzylidene-.beta.-D-glucopyranoside, compound 41. 
Step (B)--Preparation of 8-Methoxycarbonyloctyl-2-acetamido-3-O-(3, 
6-di-O-sulfo-.beta.-D-galactopyranosyl)-2-deoxy-4,6-O-benzylidene-.beta.-D 
-glucopyranoside disodium salt (compound 42) 
To a solution of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.beta.-D-galactopyranosyl)-2-deoxy 
-4,6-O-benzylidene-.beta.-D-glucopyranoside (compound 41) (1.5 g, 2.34 
mmol) (prepared as described above) in pyridine (7.5 mL) at 0.degree. C. 
was added SO.sub.3 -pyridine complex (4.0 equivalent). The reaction 
mixture was stirred for 5 hours at room temperature, quenched by adding 
methanol (2 mL), and evaporated to dryness. The residue was 
chromatographed on Iatrobeads, eluting with 
dichloromethane-methanol-pyridine (9:1:0.5), to provide compound 42 (700 
mg, 35%) after conversion to a sodium salt using the procedures described 
earlier. 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(3,6-di-O-sulfo-.beta.-D-galactopyr 
anosyl)-2-deoxy-.beta.-D-glucopyranoside disodium salt (compound 43) 
Compound 42 (550 mg, 0.65 mmol) was dissolved in methanol (50 mL) and 
hydrogenolysed in the presence of 5 % palladium on carbon (550 mg) using 
the procedure described previously. The mixture was filtered, evaporated 
and chromatographed on an Iatrobeads column, eluted with 
dichloromethane-methanol-water-pyridine (80:20:2:2), to provide compound 
43 (350 mg, 71 %) after conversion to the sodium salt as described above. 
Example 11 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(3,6-diphospho-.beta.-D-galactopyra 
nosyl)-2-deoxy-.beta.-D-glucopyranoside tetrasodium salt (compound 45) 
The synthesis of compound 45 is illustrated in FIG. 4. 
To a solution of compound 41 (1.2 g, 1.87 mmol) (prepared as described 
above) in pyridine (10.0 mL) at 0.degree. C. was added 
dimethylaminopyridine (1.5 eq) and diphenylphosphorochloride (4.0 eq). The 
resulting mixture was stirred at 0.degree. C. for 5 hours and then diluted 
with dichloromethane (100 mL), washed with cold 5% HCl solution 
(2.times.100 mL), saturated sodium bicarbonate solution (2.times.100 mL) 
and water (2.times.100 mL), dried over sodium sulfate, filtered and 
evaporated to dryness. The residue was chromatographed on silica gel, 
eluting with dichloromethane-methanol (95:5), to provide compound 44 (850 
mg, 41 %). 
Compound 44 (750 mg, 0.68 mmol) was hydrogenolyzed in the presence of 
PtO.sub.2 on carbon (750 mg) in methanol using standard procedures and 
work-up conditions to provide deblocked phospho-Le.sup.c, compound 45 (400 
mg, 73%). 
Example 12 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3,4, 
6-tri-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
trisodium salt (compound 48) 
The synthesis of compound 48 is illustrated in FIG. 5. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-3,4,6-tri-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-6-O-ben 
zyl-.beta.-glucopyranoside trisodium salt (compound 47) 
To a solution of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O--.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-gluc 
opyranoside (46) (2.5 g, 2.36 mmol) (prepared as described by Srivastava, 
et al..sup.23) in pyridine (15.0 mL) at 0.degree. C. was added SO.sub.3 
-pyridine complex (5 eq). This reaction mixture was stirred at 0.degree. 
C. for 0.5 hours and then overnight at room temperature. The mixture was 
then quenched with methanol (5.0 mL), evaporated and the residue 
chromatographed on Iatrobeads using dichloromethane-methanol-pyridine 
(9:1:0.5) and dichloromethane-methanol-water-pyridine (80:20:2:0.5) as an 
eluent to provide compound 47 (1.0 g, 31%) as a syrup. 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-(3,4 
,6-tri-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
trisodium salt (compound 48) 
Compound 47 (800 mg, 0.59 mmol) was hydrogenolyzed with palladium on carbon 
(800 mg) using the procedures and work-up conditions as described above to 
provide compound 48 (400 mg, 67%) as the sodium salt. 
Example 13 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-2-O-(-.alpha.-L-fucopyranosyl)-.beta.-D-galactopyranosyl!-2-deoxy-.be 
ta.-D-glucopyranoside sodium salt (compound 52) 
The synthesis of compound 52 is illustrated in FIG. 6. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-3-benzoyl-4,6-O-benzylidene-2-O-(3,4,6-tri-O-benzyl-.alpha.- 
L-fucopyranosyl)-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glu 
copyranoside (compound 49) 
Compound 49 was prepared by selective benzoylation at the 3' of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-O-benzyl-2-de 
oxy-.beta.-D-glucopyranoside (prepared as described by Srivastava.sup.31) 
followed by fucosylation at the 2' position using CuBr.sub.2 /DMF 
catalyzed reaction conditions and tribenzyl thiofucose as the glycosyl 
donor in methylene chloride. 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-O-benzylidene-2-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucopyra 
nosyl)-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranosi 
de (compound 50) 
To a solution of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-3-O-benzoyl-4,6-O-benzylidene-2-O-(3,4,6-tri-O-benzyl-.alpha 
.-L-fucopyranosyl)-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-g 
lucopyranoside (compound 49) (1.45 g, 0.87 mmol) (prepared by as above) 
(1.45 g, 0.87 mmol) in dichloromethane was added sodium methoxide (0.5M 
solution) in methanol and the resulting solution was stirred for 5 hours 
at room temperature. The mixture was then neutralized with resin, filtered 
and evaporated to dryness to obtain compound 50 (1.2 g, 88%) which was 
used without further purification. 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-3-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucopyranosyl)-4- 
O-4,6-O-benzylidene-3-O-sulfo-2-O-(3,4,6-tri-O-benzyl-.alpha.-L-fucopyrano 
syl)-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 51) 
To a solution of compound 50 (150 mg, 0.096 mmol) in pyridine (2.0 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (30.5 mg, 0.19 mmol). 
The resulting mixture was stirred for 20 minutes at 0.degree. C. and then 
overnight at room temperature. Standard work-up procedures as described 
above gave a residue which was chromatographed on Iatrobeads, eluting with 
dichloromethane-methanol-pyridine (95:5:0.5), to provide compound 51 (135 
mg, 84%). 
Step (D)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-2-O-(.alpha.-L-fucopyranosyl)-.beta.-D-galactopyranosyl!-2-deoxy-.bet 
a.-D-glucopyranoside sodium salt (compound 52) 
Blocked sulfo-tetrasaccharide 51 (120 mg, 0.072 mmol) was hydrogenolyzed 
over palladium on carbon (120 mg) using the procedures and work-up 
conditions described above to provide for compound 52 (54 mg, 79%). 
Example 14 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-ch 
loro-6-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-.beta.-D-glucopyranoside 
sodium salt (compound 60) 
The synthesis of compound 60 is illustrated in FIG. 7. 
Step (A)--Preparation of 6-Chloro-6-deoxy-1,2,3,4-tetra-O-acetyl-glucose 
(compound 54) 
1,2,3,4-Di-O-isopropylidene-D-galactopyranose (compound 53) (11.33 g, 43.6 
mmol) was dissolved in 200 mL of dry pyridine and cooled to -40.degree. C. 
Sulfuryl chloride (11 mL) was added and the reaction mixture was stirred 
at -40.degree. C. for 1 hour. The reaction was then warmed to room 
temperature and stirring was continued for 3 hours at room temperature. 
Dichloromethane (1 L) was added and the resulting solution was washed with 
a saturated solution of sodium bicarbonate and twice with water. The 
solvent was evaporated and the residue was chromatographed on a silica gel 
column using hexane-ethyl acetate (5:1) as the eluent. The isolated 
product was dissolved in 200 mL of 90% trifluoroacetic acid and the 
resulting mixture was stirred at room temperature for 1 hour and then 
evaporated and co-evaporation with toluene. The residue was then 
acetylated in a mixture of pyridine-acetic anhydride (1:1, 300 mL) for 20 
hrs. After standard work-up conditions, the residue was chromatographed, 
eluting with hexane-ethyl acetate (3:1), to provide 
tetra-O-acetyl-6-chloro-6-deoxy-D-galactopyranose (compound 54) (6.36 g, 
40%) as a foam. 
Step (B)--Preparation of 
O-(2,3,4Tri-O-acetyl-6-Chloro-6-deoxy-.alpha.-D-glucopyranosyl) 
Trichloroacetimidate (compound 55) 
To a solution of tetra-O-acetyl-6-chloro-6-deoxy-D-galactopyranose 
(compound 54) (6.36 g, 17.3 mmol) in DMF (60 mL) was added hydrazine 
acetate (2.4 g, 26.0 mmol). The mixture was stirred for 1 hour at room 
temperature and then 1 L of dichloromethane was added and the resulting 
solution washed 4 times with water. The organic layer was dried over 
anhydrous sodium sulfate and evaporated. Flash column chromatography using 
hexane-ethyl acetate (1:1) as the eluent gave 
2,3,4-tri-O-acetyl-6-chloro-6-deoxy-.alpha.-D-galactopyranose (5.79 g). 
This material was dissolved in 50 mL of dichloromethane and cooled to 
0.degree. C. Trichloroacetonitrile (8.93 mL, 89.2 mmol) was added followed 
by DBU (1.33 mL, 8.9 mmol). This solution was stirred for 1.5 hours and 
then evaporated. The residue was chromatographed on a silica gel column, 
eluting with hexane-ethyl acetate (2:1), to provide compound 55 (4.1 g, 
51%) as a foam. 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranoysl)-4-O-6-chloro-6-deoxy-2,3,4-tri-O-acetyl-.beta.-D-galactopyranosy 
l!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 57) 
To a solution of compound 56 (9.7 g, 10.8 mmol) (prepared by the procedure 
described by Srivastava, et al..sup.23) in 35 mL of dichloromethanediethyl 
ether (1:2), stirred under nitrogen, was added imidate 55 (10.3 g 21.9 
mmol) and then an additional 10 mL of dichloromethane-ether (1:2). The 
resulting mixture was cooled to -10.degree. C. to -15.degree. C. at which 
temperature a gel type mass formed. Dichloromethane was added until the 
solution became clear and then 3.5 mL of BF.sub.3 -etherate solution was 
added dropwise and stirring was continued for 1 hour at low temperature. 
The reaction mixture was then diluted with dichloromethane and washed with 
water, saturated NaHCO.sub.3 solution and water. The resulting solution 
was dried over anhydrous sodium sulfate and evaporated. The residue was 
chromatographed on a silica gel column, eluting with hexane-ethyl acetate 
(1:1), to provide compound 57 (12.09 g, 93%) as a white foam. 
Step (D)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopy 
ranosyl)-4-O-6-chloro-6-deoxy-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deox 
y-.beta.-D-glucopyranoside (compound 58) 
To a solution of compound 57 (5 g, 4.12 mmol) in 160 mL of methanol was 
added 10 mL of a 0.5N solution of sodium methoxide in methanol. The 
resulting mixture was stirred at room temperature overnight and then 
neutralized with Amberlite IR-120 (H.sup.+) resin, filtered and 
evaporated. The residue was chromatographed on a silica gel column, 
eluting with dichloromethane-methanol (97:3), to provide compound 58 (3.93 
g, 87%). 
Step (E)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-chloro-6-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-be 
nzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 59) 
To a solution of compound 58 (3.92, 3.63 mmol) in pyridine (50 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (860 mg, 1.5 eq). The 
resulting mixture was stirred at 0.degree. C. for 0.5 hours and then 
allowed to warm to room temperature while stirring. After 0.5 hours at 
room temperature, 0.5 eq. of SO.sub.3 -pyridine complex was added. An 
additional 0.5 eq. of SO.sub.3 -pyridine complex was added after 1.5 
hours. After 3 hours, the reaction was terminated by adding methanol. The 
solvent was evaporated and the resulting residue was chromatographed on a 
silica gel column, eluting with dichloromethane-methanol-pyridine 
(95:5:05). After evaporation, the product was dissolved in methanol and 
passed through Bio-Rex.RTM. 70 resin (100-200 mesh, sodium form) using 
methanol as an eluent to provide compound 59 (2.82 g, (66%). 
Step (F)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-ch 
loro-6-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl)!-.beta.-D-glucopyranoside 
sodium salt (compound 60) 
To a solution of compound 59 (537 mg, 0.46 mmol) in methanol (50 mL) was 
added (530 mg) of 5% Pd/C. The resulting mixture was hydrogenolyzed at 
room temperature for 2.5 hours at atmospheric pressure and then filtered 
and evaporated. The residue was chromatographed on an Iatrobead column, 
eluting with dichloromethane-methanol-water-pyridine (80:20:2:0.5). The 
fractions were pooled and evaporated and passed through Bio-Rex.RTM. 70 
Resin (100-200 mesh, sodium form) using methanol as an eluent. 
Freeze-drying gave compound 60 (285 mg, 76%) as a white solid. 
Example 15 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-6-de 
oxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 63) 
The synthesis of compound 63 is illustrated in FIG. 7. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-deoxy-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta. 
-D-glucopyranoside (compound 61) 
A mixture of compound 57 (6.1 g, 5.1 mmol), tributyltin hydride (13.6 mL, 
10 eq) and AIBN (115 mg) in toluene (250 mL) was heated at 90.degree. C. 
for 4 hours. The reaction mixture was then evaporated and the residue was 
chromatographed on a silica gel column, eluting with hexane-ethyl acetate 
(1:1), to provide crude compound 60a as a foam (.about.6.2 g with some 
impurities and tin residue). This crude material was dissolved in a 
mixture of methanol (100 mL) and dichloromethane (20 mL) and 10 mL of a 
0.5N solution of sodium methoxide in methanol was added. The reaction 
mixture was stirred overnight at room temperature and neutralized with 
Amberlite IR-120(H.sup.+) resin, filtered and evaporated. The residue was 
chromatographed on a silica gel column, eluting with 
dichloromethane-methanol (95:5), to provide compound 61 (4.42 g, 83%) as a 
white foam. 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2-d 
eoxy-.beta.-D-glucopyranoside sodium salt (compound 62) 
To a solution of compound 61 (4.42 g, 4.2 mmol) in 50 mL of pyridine at 
0.degree. C. was added SO.sub.3 -pyridine complex (1 g, 1.5 eq). The 
reaction mixture was stirred for 0.5 hours at 0.degree. C. and then 
allowed to warm to room temperature. After 0.5 hours at room temperature, 
0.5 eq. of SO.sub.3 -pyridine complex was added followed by an additional 
0.5 eq. after 1.5 hours. After 3 hours, the reaction was terminated by 
adding methanol and the solvents were evaporated. The residue was 
chromatographed on a silica gel column, eluting with 
dichloromethane-methanol (95:5) containing 2 mnL of pyridine per 1 L of 
solvent, and the resulting product was passed through Bio-Rex.RTM. 70 
Resin (100-200 mesh, sodium form) using methanol as an eluent to provide 
compound 62 (2.65, 55%). 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)4-O-6-deo 
xy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 63) 
A mixture of compound 62 (562 mg, 0.49 mmol) and 560 mg of 5% Pd/C in 50 mL 
of methanol was hydrogenolyzed for 2 hours under standard conditions. The 
mixture was then filtered, evaporated and chromatographed on an Iatrobead 
column, eluting with dichloromethane-methanol-water (80:20:2) containing 
pyridine (2 mL per 1 L of eluent), to provide a product which was then 
passed through Bio-Rex.RTM. 70 Resin (100-200 mesh, sodium form) using 
water as an eluent. The resulting solution was freeze-dried to provide 
compound 63 (216 mg, 56%). 
Example 16 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4-ch 
loro-4-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyr 
anoside sodium salt (compound 77) 
The synthesis of compound 77 is illustrated in FIG. 8. 
Step (A)--Preparation of Methyl 
4,6-O-Benzylidene-2,3-di-O-benzoyl-.alpha.-D-glucopyranoside (compound 65) 
To a mixture of 25 g (0.13 mmol) of methyl-.alpha.-D-glucopyranoside (64) 
(commercially available from Aldrich Chemical Co., Milwaukee, Wis., USA) 
in 750 mL of acetonitrile was added .alpha..alpha.-dimethoxytoluene (20 
mL) and p-toluenesulfonic acid (600 mg). The resulting mixture was stirred 
at room temperature for 20 hours and then neutralized with triethylamine 
and evaporated. The residue was dissolved in pyridine (200 mL) and cooled 
in an ice bath. Benzoyl chloride (5 eq) was then added and the mixture was 
stirred overnight at room temperature. After standard work-up procedures, 
compound 65 (44.2 g, 70%) was crystallized from a mixture of ethyl acetate 
and ether. 
Step (B)--Preparation of Methyl 
6-O-Benzyl-2,3-di-O-benzoyl-.alpha.-D-glucopyranoside (compound 66) 
A mixture of methyl 
4,6-O-benzylidene-2,3-di-O-benzoyl-.beta.-D-glucopyranoside (compound 65) 
(16.3 g, 33.2 mmol), sodium cyanoborohydride (42.9 g, 0.68 mmol), 3A 
molecular sieves and crystals of methyl orange in 500 mL of 
tetrahydrofuran was stirred at 0.degree. C. while diethyl ether saturated 
with hydrogen chloride was added until the solution became pink and 
evolution of gas ceased. After 1 hour, tic indicated that the starting 
material had been consumed. The reaction mixture was then poured into a 
cold mixture of dichloromethane and a saturated aqueous solution of sodium 
bicarbonate. The organic layer was separated and washed with saturated 
sodium bicarbonate solution and water (5 times), then dried over anhydrous 
sodium sulfate and evaporated to provide crude methyl 
6-O-benzyl-2,3-di-O-benzoyl-.alpha.-D-glucopyranoside (compound 66) as a 
white solid which was used in the next step without further purification. 
Step (C)--Preparation of Methyl 6-O-Benzyl-2, 
3-di-O-benzoyl-4-chloro-4-deoxy-.alpha.-D-glucopyranoside (compound 67) 
To a solution of crude methyl 
6-O-benzyl-2,3-di-O-benzoyl-.alpha.-D-glycopyranoside (compound 66) (from 
previous step) in 300 mL of pyridine at -40.degree. C. was added sulfuryl 
chloride (15 mL). After 1 hour, the cooling bath was removed and stirring 
was continued at room temperature for 3 hours. Dichloromethane was then 
added and the resulting solution was washed with saturated sodium 
bicarbonate solution and water, dried over anhydrous sodium sulfate and 
evaporated. The residue was chromatographed on a silica gel, eluting with 
dichloromethane, to provide methyl 
6-O-benzyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-.alpha.-D-galactopyranoside 
(compound 67) (15.3 g, 90.0% --based on compound 65) as a syrup. 
Step (D)--Preparation of Acetyl 
6-O-acetyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-D-galacopyranoside (compound 
68) 
To a solution of methyl 
6-O-benzyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-.alpha.-D-galactopyranoside 
(compound 67) (14.4 g, 28.2 mmol) in 75 mL of acetic anhydride was added a 
mixture of acetic anhydride and concentrated sulfuric acid (60 mL, 13 
.mu.L of conc. H.sub.2 SO.sub.4 per 1 mL of acetic anhydride). The 
resulting mixture was stirred at room temperature overnight and then the 
solvent was evaporated under high vacuum. The residue was dissolved in 
dichloromethane and this solution was washed with saturated sodium 
bicarbonate solution and water, and evaporated. The residue was 
chromatographed on a silica gel column, eluting with hexane-ethyl acetate 
(3:1), to provide acetyl 
6-O-acetyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-D-galactopyranoside (compound 
68) (8.53 g, 62%). 
Step (E)--Preparation of 
.alpha.-(6-O-acetyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-.alpha.-D-galactopyr 
anosyl)-trichloroacetimidate (compound 69) 
A solution of acetyl 
6-O-acetyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-D-galactopyranoside (68) 
(8.53 g, 17.4 mmol) and hydrazine acetate (2.4 g, 26.0 mmol, 1.5 eq) in 70 
mL of DMF was stirred for 1 hour at room temperature. The reaction mixture 
was then evaporated, washed with water (5 times) and evaporated. The 
residue was chromatographed on a silica gel, eluting with hexane-ethyl 
acetate (2:1), to provide 
6-O-acetyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-D-galactopyranose (7.44 g, 
95.3%). This material was dissolved in dichloromethane (50 mL) and the 
resulting solution was cooled to 0.degree. C. Trichloroacetonitrile (8.3 
mL, 82.9 mmol) was added and the mixture was stirred for 2 hours. The 
solvent was then evaporated and the residue was chromatographed on a 
silica gel column, eluting with hexane-ethyl acetate (3:1), to give 
imidate 69 (6.3 g, 64%). 
Step (F)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-O-acetyl-2,3-di-O-benzoyl-4-chloro-4-deoxy-.beta.-D-galact 
opyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-galacopyranoside (compound 70) 
To a solution of compound 56 (1.98 g 2.2 mmol) (prepared by the procedure 
described by Srivastava, et al..sup.23) in 10 mL of dichloromethane-ether 
(1:2) was added imidate 69 (2.45 g, 4.13 mmol) and 4 mL of 
dichloromethane-diethyl ether (1:2). The reaction mixture was then cooled 
to -15.degree. C. to -10.degree. C. and BF.sub.3 -etherate (0.7 mL) was 
added. This mixture was stirred for 1 hour and then diluted with 
dichioromethane. The resulting solution was washed with sodium bicarbonate 
solution and water, and then evaporated to give a syrup. The syrup was 
chromatographed on silica gel, eluting with hexane-ethyl acetate (2:1) and 
(1:1), to give trisaccharide 70 (1.42 g, 49%) as a white solid. 
Step (G)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4-chloro-4-deoxy-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta. 
-D-glucopyranoside (compound 71) 
To a solution of compound 70 (1.42 g 1.1 mmol) in 20 mL of methanol was 
added 5 mL of 0.5N sodium methoxide in methanol. The reaction mixture was 
stirred at room temperature for 5 hours and then neutralized with 
Amberlite IR-120 (H.sup.+) resin, filtered and evaporated. The residue was 
chromatographed on a silica gel column, eluting with 
dichloromethane-methanol (95:5), to provide compound 71 (1.11 g, 94%). 
Step (H)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)4-O-2,3-di-O-acetyl-4-chloro-4-deoxy-6-tert-butyl-dimethylsiyl-.b 
eta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside 
(compound 72) 
A solution of compound 71 (1.05 g, 0.97 mmol) and tert-butyldimethylsilyl 
chloride (296 mg, 1.96 mmol) in pyridine (10 mL) was stirred overnight at 
room temperature. Acetic anhydride (5 mL) was added at 0.degree. C. and 
stirring was continued for 3 hours at room temperature. The solution was 
worked-up followed by chromatography using hexane-ethyl acetate (1:1) as 
an eluent gave compound 72 (1.08 g, 87%). 
Step (I)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-2,3-di-O-acetyl-4-chloro4-deoxy-.beta.-D-galactopyranosyl!-2 
-deoxy-6-O-benzyl-.beta.-5 D-glucopyranoside (compound 73) 
To a solution of compound 72 (1.07 g , 0.84 mmol) in 25 mL of THF was added 
tetrabutylammonium fluoride hydrate (399 mg 1.26 mmol). The resulting 
mixture was stirred at room temperature for 1 hour and then diluted with 
dichloromethane (100 mL), washed with water (2.times.100 mL) and 
evaporated. The residue was chromatographed, eluting with hexane-ethyl 
acetate (1:1), to provide compound 73 (815 mg, 84%). 
Step--(J) Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-2,3-di-O-acetyl-6-O-benzyl-4-chloro-4-deoxy-.beta.-D-galacto 
pyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 74) 
To a solution of compound 73 (815 mg, 0.7 mmol) in 10 mL of toluene was 
added benzyl bromide (167 mL, 1.4 mmol) and silver oxide (715 mg, 3.5 
mmol). The reaction mixture was stirred at room temperature for 24 hours 
and then filtered and evaporated. The residue was chromatographed on a 
silica gel column, eluting with hexane-ethyl acetate (1:1), to provide 
compound 74 (471 mg, 54%). 
Step (K)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-O-benzyl-4-chloro-4-deoxy-.beta.-D-galactopyranosyl!-6-O-b 
enzyl-2-deoxy-.beta.-D-glucopyranoside (compound 75) 
To a solution of compound 74 (467 mg, 0.34 mmol) in 10 mL of methanol was 
added 5 mL of 0.5N sodium methoxide in methanol. The resulting mixture was 
stirred for 3 hours at room temperature and then neutralized with 
Amberlite IR-120(H.sup.+) resin, filtered and evaporated. The residue was 
chromatographed on a silica gel, eluting with dichloromethane-methanol 
(98:2), to provide compound 75 (390 mg, 90%). 
Step (L)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-6-O-benzyl-4-chloro-4-deoxy-3-O-sulfo-.beta.-D-galactopyrano 
syl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 76) 
To a solution of compound 75 (390 mg, 0.34 mmol) in pyridine (1 mL) at 
0.degree. C. was added SO.sub.3 -Pyridine complex (80 mg, 0.5 mmol). The 
reaction mixture was allowed to warm to room temperature and additional 
SO.sub.3 -pyridine complex was added after 0.5 hours (0.5 eq) and 1 hour 
(0.5 eq). The reaction was terminated after 2 hour by adding methanol and 
the solvents were then evaporated. The residue was chromatographed on a 
silica gel column, eluting with dichloromethane-methanol (95:5) containing 
2 mL of pyridine per 1 L of solvent, to provide compound 76 (241 mg, 57%) 
after Bio-Rex.RTM. 70 Resin (sodium form) ion exchange. 
Step (M)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4-ch 
loro-4-deoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyr 
anoside sodium salt (compound 77) 
A solution of compound 76 (241 mg, 0.19 mmol) in methanol (20 mL) 
containing 240 mg of 5% Pd/C was hydrogenolyzed at room temperature for 
1.5 hours. The reaction mixture was then filtered and evaporated. The 
residue was chromatographed, eluting with dichloromethane-methanol (80:20) 
containing 2 mL of pyridine per 1 L of solvent, to provide a product which 
was passed through a Bio-Rex.RTM.70 Resin (sodium form) column using water 
as an eluent. The resulting solution was freeze-dried to give compound 77 
(135 mg, 87%). 
Example 17 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dichloro-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-.beta.-D-glucopyr 
anoside sodium salt (compound 87) 
The synthesis of compound 87 is illustrated in FIG. 9. 
Step (A)--Preparation of 3-O-Benzyl-4,6-O-benzylidene glucopyranose 
(compound 79) 
A solution of 3-O-benzyl-D-glucopyranose (78) (12.8 g, 47.4 mmol) (prepared 
by the procedure described by Finan, et al..sup.18), 
.alpha.,.alpha.-dimethoxy-toluene (10 mL) and p-toluenesulfonic acid (265 
mg) in 500 mL of acetonitrile was stirred at room temperature for 1.5 
hours. The mixture was then neutralized with triethylamine and evaporated. 
The residue was chromatographed, eluting with dichloromethane-methanol, to 
provide compound 79 (5.21 g, 31%). 
Step (B)--Preparation of Acetyl 2-O-acetyl-3-O-benzyl-D-glucopyranose 
(compound 80) 
3-O-Benzyl-4,6-O-benzylidene-D-glucopyranose (compound 79) (5.21 g, 14.5 
mmol) was acetylated in a mixture of pyridine (40 mL) and acetic anhydride 
(140 mL) at room temperature for 2 hours. After standard work-up 
procedures and evaporation of the solvent, the residue was heated with 80% 
aqueous acetic acid (500 mL) for 17 hours. Flash column chromatography 
using hexane-ethyl acetate (1:2) as an eluent gave acetyl 
2-O-acetyl-3-O-benzyl-D-glucopyranoside (compound 80) (3.5 g, 68%). 
Step (C)--Preparation of Acetyl 
2-O-Acetyl-3-O-benzyl-4,6-dichloro-4,6-dideoxy-glucopyranose (compound 81) 
To a solution of acetyl 2-O-acetyl-3-O-benzyl-D-glucopyranose (compound 80) 
(3.5 g, 9.88 mmol) in pyridine at -40.degree. C. was added a solution of 
SO.sub.2 Cl.sub.2 (100 mL) in 100 mL of pyridine. The reaction mixture was 
allowed to warm to room temperature and was stirred for 3 hours. The 
mixture was then diluted with dichloromethane (500 mL) and this solution 
was washed with water (2.times.500 mL), saturated sodium bicarbonate 
solution and water (2.times.500 mL), dried over anhydrous sodium sulfate 
and evaporated. The residue was chromatographed on a silica gel column, 
eluting with hexane-ethyl acetate (5:1), to provide acetyl 
2-O-acetyl-3-O-benzyl-4,6-dichloro-4,6-dideoxy-D-galactopyranoside 
(compound 81) (2.89 g, 75%). 
Step (D)--Preparation of Acetyl-2, 
3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-glucopyranose (compound 82) 
A solution of 
acetyl-2-O-acetyl-3-O-benzyl-4,6-dichloro-4,6-dideoxy-D-galactopyranoside 
(compound 81) (2.89 g, 7.4 mmol) in 60 mL of methanol was hydrogenolyzed 
in the presence of 1.4 g of 5% Pd/C for 3 hours. The solution was then 
filtered and evaporated and the residue was acetylated in a mixture of 
pyridine (10 mL) and acetic anhydride (10 mL). Standard work-up procedures 
and column chromatography using hexane-ethyl acetate (2:1) as an eluent 
provided acetyl 2, 
3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-D-galactopyranose (compound 82) 
(2.34 g, 92%). 
Step (E)--Preparation of 
.alpha.-(2,3-Di-O-acetyl-4,6-dichloro-4,6-dideoxy-.alpha.-D-glucopyranosyl 
)-trichloroacetimidate (compound 83) 
A solution of acetyl 
2,3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-D-galactopyranose (compound 82) 
(2.24 g, 6.5 mmol) and hydrazine acetate (903 mg) in DMF (22 mL) was 
stirred for 2 hours at room temperature. The reaction mixture was then 
diluted with dichloromethane (250 mL) and washed 4 times with water 
(4.times.250 mL), dried over anhydrous sodium sulfate and evaporated. 
Flash chromatography using hexane-ethyl acetate (1:1) as an eluent gave 
2,3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-D-galactopyranose (.about.6.88 
mmol). This compound was then dissolved in dichloromethane (20 mL) cooled 
to 0.degree. C., and trichloroacetonitrile (3.35 mL, 34.4 mmol) was added. 
After stirring at 0.degree. C. for 40 minutes, the solvent was evaporated 
and the residue was chromatographed on a silica gel column, eluting with 
hexane-ethyl acetate (5:1), to give imidate 83 (1.14 g, 39%) as a white 
solid. 
Step (F)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopy 
ranosyl)-4-O-2,3-di-O-acetyl-4,6-dichloro-4,6-dideoxy-.beta.-D-galactopyra 
nosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 84) 
To a solution of compound 56 (990 mg, 1.10 mmol) in dichloromethane-diethyl 
ether (1:2) (5 mL), stirred under nitrogen, was added dichloro imidate 83 
(997 mg, 2.94 mmol) followed by additional dichloromethane-diethyl ether 
(1:2) (2 mL). The solution was cooled to -10.degree. C. to -15.degree. C. 
over 1 hour, at which temperature a gel-type mass formed. Dichloromethane 
was added until solution became clear and then BF.sub.3 -etherate solution 
(350 .mu.L) was added dropwise. The reaction mixture was stirred for 1 
hour and then diluted with dichloromethane (250 mL), washed with 
NaHCO.sub.3 solution (2.times.250 mL) and water (2.times.250 mL), dried 
over anhydrous sodium sulfate and evaporated. The residue was 
chromatographed on a silica gel, eluting with hexane-ethyl acetate (2:1) 
and (1:1), to provide compound 84 (853 mg, 66%). 
Step (G)--Preparation of 
8-Methyoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fuco 
pyranosyl)-4-O-4,6-dichloro-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-O-ben 
zyl-2-deoxy-.beta.-D-glucopyranoside (compound 85) 
To a solution of compound 84 (402 mg, 0.34 mmol) in 20 mL of methanol was 
added 2 mL of 0.5N sodium methoxide in methanol. The resulting mixture was 
stirred at room temperature for 1 hour and then neutralized with Amberlite 
IR-120(H.sup.+) resin, filtered, evaporated under high vacuum. The residue 
was chromatographed on a silica gel column, eluting with 
dichloromethane-methanol (95:5), to provide compound 85 (358 mg, 96%). 
Step (H)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dichloro-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl 
!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (86) 
To a solution of compound 85 (356 mg, 0.32 mmol) in pyridine (7 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (70 mg, 0.44 mmol). The 
reaction mixture was stirred for 30 minutes at 0.degree. C. then the 
cooling bath was removed and stirring was continued at room temperature. 
Additional SO.sub.3 -pyridine complex was added after 1 hour (0.5 eq), 2.5 
hours (0.5 eq), 3.5 hours (0.5 eq) and 4 hours (1.5 eq). The reaction was 
then terminated after 5.5 hours by adding methanol. The solvents were 
evaporated and the residue was chromatographed on a silica gel column, 
eluting with dichloromethane-methanol (95:5) containing 2 mL of pyridine 
per 1 L of solvent, to provide compound 86 (240 mg, 63%) after 
Bio-Rex.RTM. 70 Resin (sodium form). 
Step (I)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dichloro-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-.beta.-D-glucopyr 
anoside sodium salt (compound 87) 
A solution of compound 86 (215 mg, 0.18 mmol) in 20 mL of methanol 
containing 215 mg of 5% Pd/C was hydrogenolyzed at room temperature and 
atmospheric pressure for 6 hours. The solution was then filtered and 
evaporated. The residue was chromatographed on an latrobead column using 
dichloromethane-methanol-water (80:20:2) containing pyridine (12 mL per 1 
L of solvent) as eluent. The collected material was passed through 
Bio-Rex.RTM. 70 Resin (sodium form) using water as an eluent and the 
resulting solution was freeze-dried to provide compound 87 (128 mg, 85%). 
Example 18 
Synthesis of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosi 
de sodium salt (compound 91) 
The synthesis of compound 91 is illustrated in FIG. 9. 
Step (A)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-2,3-di-O-acetyl-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-O-b 
enzyl-2-deoxy-.beta.-D-glucopyranoside (compound 88) 
A mixture of blocked di-chloro trisaccharide (compound 84) (412 mg, 0.35 
mmol), tributyltin hydride (1.88 mL, 6.98 mmol) and AIBN (20 mg) in 20 mL 
of toluene was heated at 90.degree. C. for 3 hours. The solvent was then 
evaporated and the residue was chromatographed on a silica gel column, 
eluting with hexane-ethyl acetate (2:1), to provide compound 88 (298 mg, 
77%). 
Step (B)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.b 
eta.-D-glucopyranoside (compound 89) 
To a solution of compound 88 (298 mg, 0.27 mmol) in methanol (10 mL) and 
dichloromethane (2 mL) was added a 0.5N solution of sodium methoxide in 
methanol (5 mL). After 2 hours at room temperature, the reaction mixture 
was neutralized with Amberlite IR-120(H.sup.+) resin, filtered and 
evaporated. The residue was chromatographed on a silica gel column, 
eluting with dichloromethane-methanol (95:5), to provide compound 89 (253 
mg, 91%). 
Step (C)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopy 
ranosyl)-4-O-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-benzyl-2 
-deoxy-.beta.-D-glucopyranoside sodium salt (compound 90) 
To a solution of compound 89 (253 mg, 0.23 mmol) in 5 mL of pyridine at 
0.degree. C. was added SO.sub.3 -pyridine complex (59 mg, 0.37 mmol). 
After 0.5 hours at 0.degree. C., the cooling bath was removed and stirring 
was continued at room temperature. Additional SO.sub.3 -pyridine complex 
was added after 1.5 hours (0.75 eq), 2.5 hours (0.75 eq) and 3.5 hours 
(0.75 eq). After 5 hours, the reaction was terminated by adding methanol. 
The solvents were evaporated and the residue was chromatographed on a 
silica gel column, eluting with dichloromethane-methanol (95:5) containing 
pyridine (2 mL per 1 L of solvent), to provide compound 90 (227 mg, 87%) 
after passing the recovered product through Bio-Rex.RTM. 20 Resin (sodium 
form) using methanol as an eluent. 
Step (D)--Preparation of 
8-Methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosi 
de sodium salt (compound 91) 
A solution of compound 90 (225 mg, 0.20 mmol) in 20 mL of methanol 
containing 225 mg of 5% Pd/C was hydrogenolyzed for 2 hours at room 
temperature. The solution was then filtered and evaporated. The residue 
was chromatographed on an Iatrobeads column, eluting with 
dichloromethane-methanol-water (80:20:2) containing 2 mL of pyridine per 
liter of solvent, to provide a product which was converted into its sodium 
salt by passage through Bio-Rex.RTM. 70 Resin (sodium form) using water as 
an eluent. The resulting solution was freeze-dried to give compound 91 
(147 mg, 96%). 
Example 19 
Synthesis of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4O-4-deo 
xy-3-O-sulfo-13-D-galactopyranosyl-2-deoxy-.beta.-D-glucopyranoside sodium 
salt (95) 
The synthesis of compound 95 is illustrated in FIG. 10. 
Step (A) Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-2,3-di-O-acetyl-4-deoxy-6-O-benzyl-.beta.-D-galactopyranosyl 
!-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 92) 
A mixture of blocked trisaccharide (compound 74) (374 mg, 0.30 mmol), 
tributyltin hydride (1.7 mL) and AIBN (10 mg) in 20 mL of toluene was 
heated at 90.degree. C. for 3-5 hours. The solvent was evaporated and the 
residue was chromatographed on a silica gel column eluting with 
hexane-ethyl acetate (1:1) to provide for compound 92 (325 mg, 89%). 
Step (B) Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-.alpha. 
-L-fucopyranosyl)-4O-4-deoxy-6-O-benzyl-.beta.-D-galactopyranosyl!-6-O-ben 
zyl-2-deoxy-.alpha.-D-glucopyranoside (93) 
A 0.5M solution of sodium methoxide in methanol (5.0 mL) was added to a 
soltuion of compound 92 (325 mg, 0.27 mmol) in methanol (10 mL). After 
stirring for 3 hours at room temperature, the reaction mixture was 
neutralized with Amberlite IR-120 (H.sup.+) resin, filtered and the 
solvent evaporated. The residue was chromatographed on a silica gel column 
eluting with dichloromethane-methanol (97:3) to provide compound 93 (289 
mg, 95.5%). 
Step (C) Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopy 
ranosyl)-4-O-4-deoxy-3-O-sulfo-6-O-benzyl-.beta.-D-galactopyranosyl!-6-O-b 
enzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (94) 
To a solution of compound 93 (289 mg, 0.26 mmol) in 5 mL of pyridine at 
0.degree. C. was added SO.sub.3 -pyridine complex (51 mg, 0.38 mmol) and 
the reaction mixture was stirred for 15 minutes at 0.degree. C. and then 
2-5 hours at room temperature. Additional amounts of SO.sub.3 -pyridine 
complex were added (0.7 equivalents) after 1 and 2 hours. After 5.5 hours, 
the reaction was terminated by adding methanol. The solvents were 
evaporated and the residue was chromatographed on a silica gel column, 
eluting with dichloromethane-methanol (95:5) containing pyridine (2 mL per 
1 L of solvent), to provide compound 94 (266 mg, 84.4%), after passing the 
recovered product through Bio-Rex.RTM. 70 Resin (sodium form) using 
methanol as eluent. 
Step (D) Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4-de 
oxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (95) 
A solution of compound 94 (266 mg, 0.22 mmol) in 10 mL of methanol 
containing 266 mg of 5% palladium on carbon was hydrogenolyzed for 2 hours 
at room temperature. The solution was then filtered and evaporated. The 
residue was chromatographed on an Iatrobead column, eluting with 
dichloromethane-methanol-water (80:20:2) containing a bit of pyridine (2 
mL/1 L of the solvent mixture) to provide a product which was converted 
into a sodium salt by passage through BioRex.RTM. 70 Resin (sodium form) 
using water as the eluent. The residue was freeze dried to give compound 
95 (145 mg, 86.9%). 
Example 20 
Preparation of 
2-Acetamido-2-deoxy-3-O-.alpha.-L-fucopyranosyl!-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl azide sodium salt (compound 111) 
The synthesis of compound 111 is illustrated in FIG. 11. 
Step (A) Preparation of 
2-Acetamido-2-deoxy-3-O-2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranos 
yl!-4,6-O-p-methoxybenzylldine-.beta.-D-gIucopyranosyl azide (compound 105) 
Copper (II) bromide (59.7 g, 0.268 mol, 5.0 eq.) and pulverized 4A 
molecular sieves (100 g) were added to a reaction vessel. Dry 
dichloromethane (120 mL) was syringed into the flask followed by dry DMF 
(47 mL, 10 eq.). Tetraethylammonium bromide (11.2 g, 0.0535 mol. 1.0 eq.) 
was added to the reaction flask and the greenish-black mixture was stirred 
for 30 minutes. The acceptor 
2-N-acetamido-2-deoxy-4,6-O-p-methoxybenzylidene-.beta.-D-glucopyranosyl 
azide, compound 103 (19.5 g, 0.0535 mol, 1.0 eq.), was added to the 
reaction, followed by the donor p-chlorothiophenyl 
2,3,4-tri-O-p-methoxybenzyl-.beta.-L-fucopyranoside, compound 104 (43.5 g, 
0.0668 mol, 1.25 eq.). The mixture was stirred for three hours at room 
temperature before being quenched with triethylamine until neutral (3 mL, 
pH=7). The reaction was filtered through Celite and washed with 800 mL of 
dichloromethane. The organic layer was washed 4.times.1 L with a 5% EDTA 
solution (made by mixing 150 g tetrasodium EDTA salt with 75 g of fully 
protonated EDTA, pH=7). 
The organic layer was washed once with 1.5 L of water, dried (MgSO.sub.4), 
filtered and concentrated to give a golden syrup. This syrup was 
recrystallized from ethyl acetate/hexane to give 33.1 g of compound 105 
(71%). MW 870.97 (C.sub.46 H.sub.54 O.sub.13 N.sub.4). 
Step (B) Preparation of 
2-Acetamido-2-deoxy-3-O-2,3,4-tri-O-p-methoxybenzyI-.alpha.-L-fueopyranos 
yl!-6-O-p-methoxybenzyl-.beta.-D-glucopyranosyl azide (compound 106) 
The benzylidene acetal (compound 105--23.2 g, 26.6 mmol, 1 eq.), sodium 
cyanoborohydride (16.7 g, 266 mmol, 10 eq.), 3A molecular sieves (50 g), 
and methyl orange (2 mg) were charged to a round bottom flask. THF (350 
mL) was poured into the flask and the mixture was cooled to 0.degree. C. A 
solution of hydrochloric acid in ether was added in a dropwise fashion to 
the reaction mixture until a pink color persisted. After 3 hours, the 
reaction was quenched by pouring the mixture into 600 mL of saturated 
sodium bicarbonate solution. Dichloromethane (600 mL) was added and the 
organic layer was separated. The organic layer was washed with 3.times.500 
mL of bicarbonate solution, 1.times.500 mL water and 1.times.500 mL of a 
saturated solution of sodium chloride. The organic layer was dried 
(MgSO.sub.4), filtered and concentrated. The golden syrup was 
recrystallized from isopropanol to give 19 g (82%) of compound 106 as a 
white solid. MW 872.98 (C.sub.46 H.sub.56 O.sub.13 N.sub.4). 
Step (C) Preparation of 
2-Acetamido-2-deoxy-3-O-2,3,4-tri-O-p-methoxybenzyl-(.alpha.-L-fucopyrano 
syl!-4-O-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzyl-.beta.-D-glucopyra 
nosyl azide 
The acceptor 
2-Acetamido-2-deoxy-3-O-2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranos 
yl!-6-O-p-methoxybenzyl-.beta.-D-glucopyranosyl azide (compound 106--15.0 
g, 0.017 mol) and the donor 
2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranosyl trichloroacetimidate 
(compound 107--12.5 g, 0.025 mol, 1.5 eq.) were added to a round bottomed 
flask. Dichloromethane, 200 mL, was poured into the round bottomed flask 
and the mixture was cooled to 0.degree. C. Boron trifluoride etherate 
(1.05 mL, 8.5 mmol, 0.5 eq.) was syringed into the mixture. The reaction 
continued for eight hours and was quenched with triethylamine (0.6 mL). 
The final pH of the reaction mixture was 7. The reaction was concentrated 
and purified by silica gel chromatography. The eluent used was a step 
gradient (25%-60% ethyl acetate in hexane). Compound 108 (15.5 g, 75%) was 
obtained as a yellowish foam. MW 1203.28 (C.sub.60 H.sub.74 O.sub.22 
N.sub.4). 
The tetraacetylated galactose intermediate (compound 108--15.5 g, 0.0129 
mol) was dissolved in 200 mL of methanol. A sodium methoxide in methanol 
solution (5 mL of a 0.5M solution, 2.5 mmol, 0.2 eq) was syringed into the 
mixture. The mixture was stirred overnight and neutralized with Amberlite 
IR-120 (H.sup.+) resin. The neutralized mixture was filtered and 
concentrated. The product was purified by silica gel chromatography. The 
eluent used was 3-5% methanol in dichloromethane. The product (11.2 g, 
83%) was obtained as a white solid. MW 1035.13 (C.sub.52 H.sub.66 O.sub.22 
N.sub.4). 
Step (D) Preparation of 
2-Acetamido-2-deoxy-6-O-p-methoxybenzyl-3-O-2,3,4-tri-O-p-methoxybenzyl-. 
alpha.-L-fucopyranosyl!-4-O-4,6-O-p-methoxybenzylidene-.beta.-D-galactopyr 
anosyl!-.beta.-D-glucopyranosyl azide (compound 109) 
2-Acetamido-2-deoxy-3-O-2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosy 
l!-4-O-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzyl-.beta.-D-glucopyrano 
syl azide (11.2 g, 10.8 mmol, 1 eq.) was dissolved in 150 mL of 
acetonitrile. Anisaldehyde dimethyl acetal (3.7 mL, 22 mmol, 2 eq.) was 
syringed into the stirred mixture. Toluene sulfonic acid (50 mg) was added 
to the reaction mixture ensuring a pH of 2-3. The reaction was stirred at 
pH 2-3 for 30 minutes at room temperature. The reaction was quenched by 
neutralization with triethylamine. The solution was concentrated and 
purified by silica gel chromatography. The chromatography eluent was 2% 
methanol in dichloromethane. The product, compound 109, obtained was a 
white solid (10.2 g, 82%). MW 1153.26 (C.sub.60 H72O.sub.19 N.sub.4). 
Step (E) Preparation of 
2-Acetamido-2-deoxy-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranos 
yl)-4-O-4,6-O-p-methoxybenzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6- 
O-p-methoxybenzyI-.beta.-D-glucopyranosyl azide sodium salt (compound 110) 
2-Acetamido-2-deoxy-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosy 
l)-4-O-4,6-O-p-methoxybenzylidene-.beta.-D-galactopyranosyl!-6-O-p-methoxy 
benzyl-.beta.-D-glucopyranosyl azide (compound 109--4.02 g, 3.49 mmol, 1 
eq.) was dissolved in pyridine (40 mL) and cooled to 0.degree. C. Sulfur 
trioxide pyridine complex (1.11 g, 6.97 mmol, 2 eq) was added to the 
reaction mixture. The reaction was slowly allowed to reach room 
temperature. After 90 minutes another portion of sulfur trioxide pyridine 
complex was added (0.28 g, 0.5 eq.). After a total reaction time of three 
hours, the reaction was quenched by the addition of 2 mL of methanol. The 
solution was concentrated and purified by silica gel chromatography. The 
chromatographic eluent was 5% methanol in dichloromethane with 0.5% added 
pyridine. After purification, the product was concentrated and passed 
through 50 g of analytical grade Na.sup.+ ion exchange resin using 
methanol as the eluent. The product was concentrated to give compound 110 
as a white solid (3.98 g, 92%). MW 1255.30 (C.sub.60 H.sub.71 O.sub.22 
N.sub.4 SNa). 
Step (F) Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl azide sodium salt (compound 111) 
2-N-Acetamido-2-deoxy-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyrano 
soyl)-4-O-4,6-O-p-methoxybenzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!- 
6-O-p-methoxybenzyl-.beta.-D-glucopyranosyl azide sodium salt (1.0 g, 0.797 
mmol) was dissolved in 30 mL of 90% aqueous acetonitrile. The reaction 
mixture was cooled to 0.degree. C. and ceric ammonium nitrate (3.5 g, 6.4 
mmol, 8 eq.) was added to the mixture all at once. The reaction was 
gradually warmed to room temperature and quenched at 6.5 hours by the 
addition of pyridine. The reaction required 1.7 mL of pyridine for 
complete neutralization. The product was concentrated, and purified by 
column chromatography using Iatrobead silica gel. The chromatographic 
eluent was 70:30:3:1 dichloromethane:methanol:water:pyridine. The product 
was concentrated to dryness and passed through 40 g of analytical grade 
Na.sup.+ ion exchange resin. The product was then filtered through a 
0.22.mu. Millipore filter and lyophilized. The product, compound 111, was 
isolated as a fluffy white solid (443 mg, 85%). MW 656.56 (C.sub.20 
H.sub.33 O.sub.17 N.sub.4 SNa). 
Example 21 
Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl amine 
Procedure A. 
2-Acetamido-2-deoxy-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosy 
l)-4-O-4,6-O-p-methoxybenzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O 
-p-methoxybenzyl-.beta.-D-glucopyranosyl azide (compound 110--500 mg, 0.398 
mmol) was weighed into a reaction flask. The vessel was then flushed with 
nitrogen and 500 mg of 5% palladium on charcoal was added to the flask. 
Dry methanol (6.0 mL) was syringed into the flask followed by 4.0 mL of a 
0.37% methanolic hydrochloric acid solution. The mixture was then purged 
with hydrogen gas and remained under hydrogen atmosphere for four hours at 
room temperature. At this time, another 1.0 mL of acidic solution was 
added to the reaction (total mmols of HCl=0.51, 1.28 eq.). The reaction 
was stirred an additional four hours and quenched by the addition of 
pyridine until the pH of the solution was basic. The reaction solution was 
then filtered and the catalyst washed well with water and methanol. The 
solution was concentrated on a rotary evaporator (water bath&lt;25.degree. 
C.) and purified by column chromatography (Iatrobeads 85:10:5 
isopropanol:water:ammonia was the eluant). The total time the product was 
in contact with silica gel was three hours. The product was collected, 
pyridine added to the collection flask and concentrated as noted above. 
The product was then loaded onto 8 g of Na.sup.+ analytical grade ion 
exchange resin and lyophilized to yield 191 mg (75%) of a fluffy white 
powder. MW of sodium salt 630.55 (C.sub.20 H.sub.35 O.sub.17 N.sub.2 SNa). 
NMR revealed the product was 20-30% decomposed. It was found that the 
lifetime of the product could be enhanced by using the reaction mixture 
immediately after hydrogenation. MW (pyridinium salt) 687.68 (C.sub.25 
H.sub.41 O.sub.17 N.sub.3 S.sup.-). 
Procedure B. 
2-Acetamido-2-deoxy-(3-O-.alpha.-L-fucopyranosyl!-4-O-3-O-sulfo-.beta.-D-g 
alactopyranosyl)-.beta.-D-glucopyranosyl azide (compound 111--150 mg, 0.22 
mmol) and 5% palladium on charcoal (200 mg) were added to a reaction 
vessel and purged with nitrogen. Dry methanol (10 mL) was syringed into 
the flask and the reaction contents were cooled to 0.degree. C. The 
reaction vessel was then purged with hydrogen gas and stirred at 0.degree. 
C. for two hours. The reaction was quenched by the addition of pyridine, 
filtered and concentrated. Caution was used to maintain all procedures at 
or below room temperature to reduce risk of product decomposition. The 
crude product was used directly for further chemical manipulations without 
any characterization. Tic of the reaction mixture when complete indicates 
a major product spot at Rf=0.30 (75:20:5 isopropanol:water:ammonia) with a 
minor spot at Rf=0.20 (approximately 20% as intense as the product spot by 
sulfuric acid charring). 
Example 22 
Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
gaIactopyranosyl!-.beta.-D-glucopyranosyl benzamide sodium salt 
The crude glycosyl amine (190 mg, 0.28 mmol--pyridinium salt from Example 
21--Procedure A) was dissolved in 8.5 mL of methanol and 3.0 mL of a 
saturated solution of sodium bicarbonate. The reaction mixture was cooled 
to 0.degree. C. and benzoyl chloride (0.175 mL, 1.5 mmol, 5.4 eq.) was 
syringed into the mixture all at once. The reaction was complete within 5 
minutes, as indicated by an increase in Rf on tic (Rf starting 
material=0.31, product=0.53 in 75:20:5 isopropanol:water:ammonia). A few 
drops of pyridine were added to the reaction mixture and it was 
concentrated under reduced pressure. The product was isolated by Iatrobead 
column chromatography using 70:30:3:1 
dichloromethane:methanol:water:pyridine as eluent. Concentration of the 
product was followed by ion exchange chromatography using 10 g of 
analytical grade Na.sup.+ resin. Lyophilization yielded 122 mg of product 
(59%) as a fluffy white powder. MW 734.66 (C.sub.27 H.sub.39 O.sub.18 
N.sub.2 SNa). 
Example 23 
Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-40-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranosyl p-nitrobenzamide sodium salt 
The crude glycosyl amine (335 mg, 0.49 mmol--pyridinium salt from Example 
21--Procedure A) was dissolved in 15 mL of methanol and 5 mL of a 
saturated solution of sodium bicarbonate. The reaction mixture was cooled 
to 0.degree. C. and p-nitrobenzoyl chloride (698 mg, 3.8 mmol, 7.7 eq.) 
was added to the reaction mixture. Acetone (1 mL) was syringed into the 
mixture to enhance the solubility of the acid chloride. The reaction was 
stirred overnight at room temperature. A few drops of pyridine was added 
to the reaction and the mixture was concentrated. The product was purified 
as described for the preparation of the benzamido product (Example 22). 
The chromatography eluent was 70:30:3:1 
dichloromethane:methanol:water:pyridine. The product, 88 mg (23%), was 
obtained as a fluffy white solid. MW 779.66 (C.sub.27 H.sub.38 O.sub.20 
N.sub.3 SNa). 
Example 24 
Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl butyramide sodium salt 
The crude glycosyl amine (292 mg, 0.42 mmol--pyridinium salt from Example 
21--Procedure A) was dissolved in 12 mL of methanol and 4 mL of a 
saturated solution of sodium bicarbonate. The reaction mixture was cooled 
to 0.degree. C. and butyric anhydride (0.39 mL, 2.4 mmol, 5.7 eq.) was 
added to the reaction mixture. After 5 minutes, a few drops of pyridine 
was added to the reaction and the mixture was concentrated. The product 
was purified as described for the preparation of the benzamido product 
(Example 22). The chromatography eluent was 70:30:2:1 
dichloromethane:methanol:water:pyridine. A second column using 85:10:5 
isopropanol:water:ammonia was used to repurify the product. The product, 
90 mg (30%), was obtained as a fluffy white solid. MW 700.65 (C.sub.24 
H.sub.41 O.sub.18 N.sub.2 SNa). 
Example 25 
Preparation of 
2-Acetamido-2-deoxy-3-(.alpha.-L-fucopyranosyl)-40-3-O-sulfo-.beta.-D-gal 
actopyranosyl!-.beta.-D-glucopyranosyl acetamide sodium salt 
The crude glycosyl amine (135 mg, 0.20 mmol--pyridinium salt from Example 
21--Procedure A) was dissolved in 4.5 mL of methanol and 1.5 mL of a 
saturated solution of sodium bicarbonate. The reaction mixture was cooled 
to 0.degree. C. and acetic anhydride (0.095 mL, 1.0 mmol, 5 eq.) was added 
to the reaction mixture. After several hours, a few drops of pyridine were 
added to the reaction and the mixture was concentrated. The product was 
purified as described for the preparation of the benzamido product 
(Example 22). The chromatography eluent was 85:11:4 
isopropanol:water:ammonia. A second column was used to repurify the 
product (eluent was 70:30:2.5:1 dichloromethane:methanol:water:pyridine). 
The product, 118 mg (88%), was obtained as a fluffy white solid. MW 672.59 
(C.sub.22 H.sub.37 O.sub.18 N.sub.2 SNa). 
Example 26 
Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl stearamide sodium salt 
Stearic acid (564 mg, 2.0 mmol, 9 eq.) and dicyclohexylcarbodiimide (590 
mg, 2.9 mmol, 13 eq.) were weighed into a reaction flask. Methanol (70 mL) 
was added to the flask and the mixture was stirred at 0.degree. C. for 30 
minutes. The crude glycosyl amine (158 mg, 0.23 mmol, 1 eq.--pyridinium 
salt from Example 21--procedure B) was dissolved in 2.times.5 mL of 
methanol and added to the reaction flask. The reaction was stirred 
overnight at room temperature and then a few drops of pyridine were added 
to the reaction flask. The mixture was then concentrated and purified as 
described for the preparation of the benzamido product (Example 22). The 
chromatography eluent was 80:20:2 dichloromethane:methanol:pyridine. The 
product, 62 mg (30%), was obtained as a fluffy white solid. MW 897.02 
(C.sub.38 H.sub.69 O.sub.18 N.sub.2 SNa). 
Example 27 
Preparation of 
2-Acetamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl L-serine sodium salt 
N-Benzyloxycarbonyl-L-serine (450 mg, 1.9 mmol, 9 eq.) and EDC (560 mg, 2.9 
mmol, 14 eq.) were weighed into a reaction flask. Methanol (65 mL) was 
added to the flask and the mixture was stirred at 0.degree. C. for 30 
minutes. The crude glycosyl amine (142 mg, 0.21 mmol, 1 eq--pyridinium 
salt from Example 21 procedure B) was dissolved in 2.times.5 mL of 
methanol and added to the reaction flask. The reaction was stirred 
overnight at room temperature and then a few drops of pyridine were added 
to the reaction flask. The mixture was then concentrated and purified as 
described for the preparation of the benzamido product (Example 22). The 
chromatography eluent was 70:30:2:0.1 
dichloromethane:methanol:water:pyridine. The benzyloxycarbonyl protected 
product, 115 mg (64%), was obtained as a fluffy white solid. MW 851.77 
(C.sub.31 H.sub.46 O.sub.21 N.sub.3 SNa). 
The benzyloxycarbonyl protected product (115 mg, 0.13 mmol) was added to a 
reaction flask followed by 200 mg of 5% palladium on charcoal. The flask 
was argon purged and then methanol (10 mL) was added. The reaction flask 
was then purged with hydrogen for one hour at room temperature. Tlc of the 
reaction after one hour indicated the reaction was complete. Several drops 
of pyridine were added to the reaction and the catalyst was removed by 
filtration. The filtrate was concentrated and purified as described for 
the preparation of the benzamido product (Example 22). The chromatography 
eluent was 65:35:4:0.1 dichloromethane:methanol:water:pyridine. The 
glucopyranosyl serine product was obtained after lyophilization as a 
fluffy white solid (60 mg, 62%). MW 717.64 (C.sub.23 H.sub.40 O.sub.19 
N.sub.3 SNa). 
Example 28 
Preparation of 
8-methoxycarbonyloctyl-2-acetamido-2-deoxy-3-O-(4-deoxy-.alpha.-L-fucopyra 
nosyl)-4-O-(3-O-sulfo-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside 
sodium salt (compound 212) 
The synthesis of this compound is illustrated in FIG. 12. 
Step A--Preparation of Methyl 2-O-benzyl-L-fucopyranoside, compound 201 
The title compound, compound 201, was prepared according to Deter-Jusynski, 
et al..sup.36 
Step B--Preparation of Methyl 2,3-di-O-benzyl-L-fucopyranoside (compound 
202) 
A mixture of compound 201 (7 g, 26.089 mmol), di-n-butyltin oxide (7 g, 
28.12 mmol) in anhydrous benzene (300 mL) was boiled under reflux with 
azetropic removal of water for 6 hours and then concentrated to 50 mL. 
Tetrabutylammonium fluoride monohydrate (9.8 g, 37.48 mmol), 4A molecular 
sieves (23 g) and benzyl bromide (9.25 mL, 77.77 mmol) were then added and 
the mixture was kept at room temperature overnight. Column chromatography 
on silica gel (hexane-ethyl acetate, 2:1) gave compound 202 (9.1 g, 97%). 
Step C--Preparation of Methyl 
2,3-di-O-benzyl-4-O-(methylthio)thiocarbonyl-L-fucopyranoside (compound 
203) 
Sodium hydride (428 mg, 60% in mineral oil, 10.7 mmol) and imidazole (10 
mg) were added to compound 202 (750 mg, 2.092 mmol) in THF (16 mL). The 
reaction mixture was heated at 50.degree. C. for 0.5 hours and carbon 
disulfide (16 mL) was added. In another 1 hour, methyl iodide (16 mL) was 
added. Heating was continued for 1 more hour and the mixture was cooled to 
room temperature and methanol was added. Concentration and then column 
chromatography (hexane-ethyl acetate, 3:1) gave compound 203 (850 mg, 
90%). 
Step D--Preparation of Methyl 
2,3-di-O-benzyl-4-O-(imidazole)thiocarbonyl-L-fucopyranoside (compound 
204) 
A mixture of compound 202 (8 g, 22.32 mmol) and 
1,1'-thiocarbonyldiimidazole (9 g, 50.50 mmol) in 1,2-dichloroethane (100 
mL) was refluxed for 4 hours and then concentrated. Column chromatography 
of the residue (hexane-ethyl acetate, 2:1, 1:1) yielded compound 204 (10.1 
g, 96%). 
Step E--Preparation of Methyl 2,3-di-O-benzyl-4-deoxy-L-fucopyranoside 
(compound 205) 
Preparation A (from compound 203) 
Compound 203 (850 mg, 1.895 mmol) in anhydrous toluene (20 mL) was heated 
at 80.degree. C. AIBN (350 mg, 2.142 mmol) was added followed by 
tributyltin hydride (8 mL, 29.74 mmol). Heating was continued for 2 hours 
and the mixture was concentrated and chromatographed (hexane-ethyl 
acetate, 3:1) to give compound 205 (620 mg, 95%). 
Preparation B (from compound 204) 
Compound 204 (10 g, 21.3 mmol) in anhydrous toluene (160 mL) was heated at 
100.degree. C. AIBN (2.6 g, 15.912 mmol) and tributyltin hydride (50 g, 
171.8 mmol) were then added. Heating was continued for 2 hours and the 
mixture was concentrated and chromatographed (hexane-ethyl acetate, 6:1) 
to give compound 205 (5.4 g, 74%). 
Step F--Preparation of 2,3-Di-O-benzyl-4-deoxy-L-fucopyranose (compound 
206) 
Compound 205 (10 g, 29.2 mmol) in glacial acetic acid (180 mL) and 6N HCl 
(36 mL) was heated at 65.degree. C. for 3 hours and evaporated. The crude 
product, compound 206, was used in the next reaction without purification. 
Step G--Preparation of p-Chlorophenyl 
2,3-di-O-benzyl-4-deoxy-.beta.-L-thiofucopyranoside (compound 207) 
A mixture of compound 206 (29.2 mmol), anhydrous NaOAc (2.5 g, 30.48 mmol) 
and acetic anhydride (53 mL) in 1,2-dichloroethane (90 mL) was heated at 
60.degree. C. for 3 hours and cooled to room temperature. Water was added 
and the organic layer was separated and washed with water and aqueous 
sodium bicarbonate. After concentration, the dried residue was dissolved 
in dichloromethane (100 mL) and the mixture was cooled at 0.degree. C. 
p-Chlorothiophenol (4.5 g, 31.116 mmol) was added followed by BF.sub.3 
-ether (7.3 mL). The reaction mixture was allowed to reached room 
temperature and kept there for 1.5 hours. It was then poured into 
ice-NaHCO.sub.3 and extracted with dichloromethane. Column chromatography 
(hexane-ethyl acetate, 6:1) of the residue on evaporation gave compound 
207 (10.5 g, 79% 3-steps). 
Step H--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-4-O-(2,3-di-O-benzoyl-4,6-O-benzylidene-.beta.-D-ga 
lactopyranosyl)-2-deoxy-.beta.-D-glucopyranoside (compound 208) 
Compound 208 was prepared according to the procedures provided in 
International patent application Ser. No. PCT/US93/04909 which is 
incorporated herein by reference in its entirety. 
Step I--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-2-deoxy-3-O-(2,3-di-O-benzyl-4-deoxy-.alpha.-L-fuco 
pyranosyl)-4-O-(2,3-di-O-benzoyl-4,6-O-benzylidene-.beta.-D-galactopyranosy 
l)-.beta.-D-glucopyranoside (compound 209) 
DMF (3 mL) and tetraethylammonium bromide (768 mg, 3.654 mmol) were added 
to a suspension of copper bromide (4.17 g, 18.669 mmol) and 4A molecular 
sieves (7.2 g) in dichloromethane (6 mL). After string at room temperature 
for 0.5 hours, a solution of compound 208 (3.6 g, 3.83 mmol) in 
dichloromethane (7 mL) was added followed by compound 207 (4 g, 8.79 mmol) 
in dichloromethane (6 mL). The mixture was then kept in the dark for 16 
hours and pyridine (1 mL) was added. The resulting solution was filtered 
through Celite, concentrated and column chromatographed (hexane-acetone, 
5:2) to give compound 209 (3.5 g, 73%) 
Step J--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,3-di-O-benzyl-4-deoxy-.alpha.-L-fucopyranosy 
l)-4-O-(4,6-O-benzylidene-.beta.-D-galactopyranosyl)-2-deoxy-.beta.-D-gluco 
pyranoside (compound 210) 
Compound 209 (3.3 g, 2.64 mmol) was treated with 0.06N methanolic sodium 
methoxide (90 mL) for 16 hours. It was neutralized by Amberlite IR 120 
(H.sup.+), filtered and evaporated. Column chromatography of the residue 
(hexane-acetone, 2:1) provided for compound 210 (2.5 g, 91%). 
Step K--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,3-di-O-benzyl-4-deoxy-.alpha.-L-fucopyranosy 
l)-4-O-(4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl)-2-deoxy-.bet 
a.-D-glucopyranoside sodium salt (compound 211) 
Sulfur trioxide-pyridine complex (687 mg, 4.32 mmol) was added to compound 
210 (2.5 g, 2.4 mmol) in pyridine (16 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature and more sulfur 
trioxide-pyridine complex (300 mg, 1.885 mmol) was added. Stirring was 
continued for 1 more hour and methanol was added. After evaporation of the 
solvent, the residue was applied to a column of silica gel 
(methanol-dichloromethane, 1:9, 0.1% pyridine). The product obtained was 
then passed through a column of Amberlite IR-120 Na.sup.+ (MeOH) to give 
compound 211 (2.2 g, 80%). 
Step L--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(4-deoxy-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo-. 
beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside sodium salt (compound 
212) 
Compound 211 (1.5 g, 1.311 mmol) and palladium on carbon (5%, 2.2 g) in 
MeOH (80 mL) were hydrogenated for 3 hours and pyridine was added. After 
filtration of the catalyst and evaporation of the solvent, the crude 
product was purified by chromatography on silica gel 
(dichloromethane-methanol-water, 80:20:2, 0.2% pyridine) and then a column 
of Bio-Rex.RTM. 70 (Na.sup.+ form) to provide for compound 212 (750 mg, 
73%). 
Example 29 
Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(4-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside sodium salt (compound 
224) 
The synthesis of this compound is illustrated in FIG. 13. 
Step A--Preparation of p-Chlorophenyl 
3,4-O-benzylidene-.beta.-L-thiofucopyranoside (compound 214) 
A mixture of compound 213 (1.8 g, 6.19 mmol), p-toluenesulfonic acid (20 
mg) and .alpha.,.alpha.-dimethoxytoluene (1.6 mL, 10.66 mmol) in 
acetonitrile (10 mL) was kept at room temperature overnight and 
concentrated to 6 mL. It was then heated at 55.degree. C. for 2 hours and 
neutralized by triethylamine and evaporated to give crude compound 214 
which was used in the next reaction. 
Step B--Preparation of p-Chlorophenyl 
2-O-benzyl-3,4-O-benzylidene-.beta.-L-thiofucopyranoside (compound 215) 
Sodium hydride (383 mg, 60% in mineral oil, 9.575 mmol) was added in small 
portions to compound 214 (3.1 mmol) in DMF (4 mL) which was cooled in dry 
ice. After 0.5 hours, benzyl bromide (1.2 mL) was added and the reaction 
mixture was allowed to reach room temperature and kept there for 2 hours. 
Methanol was added to destroy the remaining NaH and the solvent were then 
removed by evaporation. The residue was taken up in dichloromethane, 
filtered through Celite and evaporated to leave crude compound 215 as a 
syrup. 
Step C--Preparation of p-Chlorophenyl 
2-O-benzyl-.beta.-L-thiofucopyranoside (compound 216) 
Compound 215 (3.0 mmol) in 80% acetic acid (20 mL) was heated at 50.degree. 
C. for 2 hours. It was evaporated and co-evaporated with toluene. 
Chromatography of the residue (hexane-ethyl acetate, 1:1) provided 
compound 216 (720 mg, 63%, 3 steps). 
Step D--Preparation of p-Chlorophenyl 
2,3-di-O-benzyl-.beta.-L-thiofucopyranoside (compound 217) 
A mixture of compound 216 (700 mg, 1.838 mmol) and di-n-butyltin oxide (495 
mg, 1.988 mmol) in benzene (40 mL) was boiled under reflux with azetropic 
removal of water for 6 hours and then concentrated to 5 mL. 
Tetrabutylammonium fluoride monohydrate (700 mg, 2.67 mmol), 4A molecular 
sieves (1.7 g) and benzyl bromide (0.7 mL, 5.89 mmol) were then added and 
the mixture was kept at room temperature overnight. Column chromatography 
on silica gel (hexane-ethyl acetate, 3:1) gave compound 217 (810 mg, 93%). 
Step E--Preparation of p-Chlorophenyl 
2,3-di-O-benzyl-4-O-(4-methoxybenzyl)-.beta.-L-thiofucopyranoside 
(compound 218) 
A solution of compound 217 (660 mg, 1.401 mmol) in DMF (6 mL) was cooled in 
dry ice and sodium hydride (584 mg, 60% in mineral oil, 14.6 mmol) was 
added in small portions. After 0.5 hours, p-methoxybenzyl chloride (1.83 
mL, 13.50 mmol) was added and the reaction mixture was then kept at room 
temperature for 3 hours. Methanol was then added. After evaporation, the 
residue was applied to a column of silica gel (hexane-ethyl acetate, 10:1) 
and the appropriate fractions collected to provide for compound 218 (605 
mg, 73%). 
Step F--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-2-deoxy-3-O-(2,3-di-O-benzyl-4-O-(4-methoxybenzyl)- 
.alpha.-L-fucopyranosyl)-4-O-(2,3-di-O-benzoyl-4,6-O-benzylidene-.beta.-D-g 
alactopyranosyl)-.beta.-D-glucopyranoside (compound 219) 
DMF (0.39 mL) and tetraethylammonium bromide (106 mg, 0.505 mmol) were 
added to a suspension of copper bromide (552 mg, 2.473 mmol) and 4A 
molecular sieves (880 mg) in dichloromethane (1 mL). After stirring at 
room temperature for 0.5 hours, a solution of compound 208 (490 mg, 0.521 
mmol) in dichloromethane (1 mL) was added followed by compound 218 (440 
mg, 0.745 mmol) in dichloromethane (1 mL). The mixture was then kept in 
the dark for 24 hours and pyridine (0.3 mL) was added. It was filtered 
through Celite, concentrated and column chromatographed (hexane-acetone, 
5:2) to give compound 219 (680 mg, 94%). 
Step G--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-2-deoxy-3-O-(2,3-di-O-benzyl-4-O-(4-methoxybenzyl)- 
.alpha.-L-fucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!- 
.beta.-D-glucopyranoside (compound 220) 
Compound 219 (670 mg, 0.483 mmol) was treated with 0.06N methanolic sodium 
methoxide (15 mL) for 16 hours. It was neutralized by Amberlite IR 120 
(H.sup.+), filtered and evaporated. Column chromatography of the residue 
(hexane-acetone, 1:1) provided compound 220 (550 mg, 97%). 
Step H--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,3-di-O-benzyl-4-O-(4methoxybenzyD)-.alpha.-L 
-fucopyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl! 
-2-deoxy-.beta.-D-glucopyranoside (compound 221) 
Sulfur trioxide pyridine complex (119 mg, 0.747 mmol) was added to compound 
220 (550 mg, 0.467 mmol) in pyridine (2 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature. Stirring was continued for 
1 more hour and methanol was added. After evaporation of the solvent, the 
crude product, compound 221, was used in the next reaction. 
Step I--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,3-di-O-benzyl-.alpha.-L-fucopyranosyl)-4-O- 
4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glu 
copyranoside (compound 222) 
A mixture of compound 221 (0.336 mmol) and CAN (460 mg, 0.839 mmol) in 
acetonitrile-water (9:1, 10 mL) was kept at room temperature for 1 hour 
and pyridine (0.6 mL) was added followed by dichloromethane. The organic 
layer was separated and washed with water. After evaporation of the 
solvent, the residue was applied to a column of silica gel 
(dichloromethane-methanol, 85:15, 0.2% pyridine) to provide for compound 
222 (350 mg, 87%, 2 steps). 
Step J--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6O-benzyl-3-O-(2,3-di-O-benzyl-4-O-sulfo-.alpha.-L-fucopyranos 
yl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.be 
ta.-D-glucopyranoside disodium salt (compound 223) 
Sulfur trioxide-pyridine complex (80 mg, 0.502 mmol) was added to compound 
222 (350 mg, 0.291 mmol) in pyridine (2.4 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature and more sulfur 
trioxide-pyridine complex (120 mg, 0.753 mmol) was added in small 
portions. Stirring was continued for 3 hours and methanol was added. After 
evaporation of the solvent, the residue was applied to a column of silica 
gel (water-methanol-dichloromethane, 2:20:80, 0.2% pyridine used as 
eluent). The product obtained was then passed through a column of 
Amberlite R-120 Na.sup.+ (MeOH) to give compound 223 (180 mg, 49%). 
Step K--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(4-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo 
-.beta.-D-galactopyranosyl!-.beta.-D-glucopyranoside disodium salt 
(compound 224) 
Compound 223 (150 mg, 0.119 mmol) and palladium on carbon (5%, 280 mg) in 
MeOH (8 mL) were hydrogenated for 2 hours and pyridine (0.8 mL) was added. 
After filtration of the catalyst and evaporation of the solvent, the crude 
product was purified by chromatography on silica gel 
(dichloromethane-methanol-water, 70:30:3, 0.2% pyridine) and then a column 
of Bio-Rex.RTM. 70 (Na.sup.+ form) to provide for compound 224 (81 mg, 
76%). 
Example 30 
Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo 
-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside disodium salt 
(compound 232) 
The synthesis of compound 232 is illustrated in FIG. 14. 
Step A--Preparation of p-Chlorophenyl 
2-O-benzyl-3-O-(4-methoxybenzyl)-.beta.-L-thiofucopyranoside (compound 
225) 
A mixture of compound 216 (660 mg, 1.732 mmol) and di-n-butyltin oxide (495 
mg, 1.988 mmol) in benzene (60 mL) was boiled under reflux with azetropic 
removal of water for 6 hours and then concentrated to 10 mL. 
Tetrabutylammonium fluoride monohydrate (660 mg, 2.524 mmol), 4A molecular 
sieves (1.7 g) and 4-methoxybenzyl chloride (0.77 mL, 5.66 mmol) were then 
added and the mixture was kept at room temperature overnight. Column 
chromatography on silica gel (hexane-ethyl acetate, 3:1) gave compound 225 
(770 mg, 89%). 
Step B--Preparation of p-Chlorophenyl 
2,4-di-O-benzyl-3-O-(4-methoxybenzyl)-.beta.-L-thiofucopyranoside 
(compound 226) 
A solution of compound 225 (750 mg, 1.497 mmol) in DMF (5 mL) was cooled in 
dry ice and sodium hydride (600 mg, 60% in mineral oil, 15 mmol) was added 
in small portions. After 0.5 hours, benzyl bromide (1.7 mL, 14 mmol) was 
added and the reaction mixture was then kept at room temperature for 2 
hours. Methanol was added. After evaporation, the residue was applied to a 
column of silica gel (hexane-ethyl acetate, 6:1) to provide for compound 
226 (705 mg, 80%). 
Step C--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-2-deoxy-3-O-(2,4-di-O-benzyl-3-O-(4-methoxybenzyl)- 
.alpha.-L-fucopyranosyl)-4-O-2,3-di-O-benzoyl-4,6-O-benzylidene-.beta.-D-g 
alactopyranosyl!-.beta.-D-glucopyranoside (compound 227) 
DMF (0.34 mL) and tetraethylammonium bromide (106 mg, 0.504 mmol) were 
added to a suspension of copper bromide (477 mg, 2.137 mmol) and 4A 
molecular sieves (760 mg) in dichloromethane (1 mL). After stirring at 
room temperature for 0.5 hours, a solution of compound 208 (300 mg, 0.319 
mmol) in dichloromethane (1.5 mL) was added followed by compound 226 (380 
mg, 0.642 mmol) in dichloromethane (1.5 mL). The mixture was then kept in 
the dark for 5 hours and pyridine (0.5 mL) was added. It was filtered 
through Celite, concentrated and column chromatographed (hexane-acetone, 
5:2) to give compound 227 (360 mg, 81%). 
Step D--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4-di-O-benzyl-3-O-(4-methoxybenzyl)-.alpha.- 
L-fucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-2-deoxy- 
.beta.-D-glucopyranoside (compound 228) 
Compound 227 (330 mg, 0.237 mmol) was treated with 0.06N methanolic sodium 
methoxide (8 mL) for 16 hours. It was neutralized by Amberlite IR 120 
(H.sup.+), filtered and evaporated. Column chromatography of the residue 
(hexane-acetone, 1:1) provided for compound 228 (255 mg, 91%). 
Step E--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4-di-O-benzyl-3-O-(4-methoxybenzyl)-.alpha.- 
L-fucopyranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl 
!-2-deoxy-.beta.-D-glucopyranoside (compound 229) 
Sulfur trioxide-pyridine complex (50 mg, 0.314 mmol) was added to compound 
228 (245 mg, 0.207 mmol) in pyridine (1.6 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature and more sulfur 
trioxide-pyridine complex (20 mg) was added. Stirring was continued for 
0.5 more hours and methanol was added. After evaporation of the solvent, 
the crude product, compound 229, was used in the next reaction. 
Step F--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4di-O-benzyl-.alpha.-L-fucopyranosyl)-4-O-4 
,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-gluc 
opyranoside (compound 230) 
A mixture of compound 229 (0.207 mmol) and CAN (400 mg, 0.730 mmol) in 
acetonitrile-water (9:1, 10 mL) was kept at room temperature for 3 hours 
and pyridine (0.6 mL) was added followed by dichloromethane. The organic 
layer was separated and washed with water. After evaporation of the 
solvent, the residue was applied to a column of silica gel 
(dichloromethane-methanol, 85:15, 0.2% pyridine) to yield compound 230 
(190 mg, 76%, 2 steps). 
Step G--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4-di-O-benzyl-3-O-sulfo-.alpha.-L-fucopyrano 
syl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.b 
eta.-D-glucopyranoside disodium salt (compound 231) 
Sulfur trioxide-pyridine complex (80 mg, 0.502 mmol) was added to compound 
230 (140 mg, 0.116 mmol) in pyridine (1 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature and more sulfur 
trioxide-pyridine complex (70 mg) was added in small portions. Stirring 
was continued for 1.5 hours and methanol was added. After evaporation of 
the solvent, the residue was applied to a column of silica gel 
(methanol-dichloromethane, 15:85, 0.2% pyridine). The product obtained was 
then passed through a column of Amberlite IR-120 Na.sup.+ (MeOH) to give 
compound 231 (110 mg, 75%). 
Step H--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-sulfo-.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo 
-.beta.-D-galactopyranosyl!-.beta.-D-glucopyranoside disodium salt 
(compound 232) 
Compound 231 (110 mg, 0.087 mmol) and palladium on carbon (5%, 150 mg) in 
MeOH (4 mL) were hydrogenated for 2 hours and pyridine (2 mL) was added. 
After filtration of the catalyst and evaporation of the solvent, the crude 
product was purified by chromatography on silica gel 
(dichloromethane-methanol-water, 70:30:3, 0.2% pyridine) and then a column 
of Bio-Rex.RTM. 70 (Na.sup.+ form) to provide for compound 232 (68 mg, 
87%). 
Example 31 
Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-methyl-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulf 
o-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside sodium salt (compound 
245) 
The synthesis of compound 245 is illustrated in FIG. 15. 
Step A--Preparation of Methyl 
2-O-Acetyl-3-O-(4-methoxybenzyl)-L-fucopyranoside (compound 234) 
A mixture of compound 233 (2.1 g, 9.5 mmol), di-n-butyltin oxide (2.6 g, 
10.446 mmol) in anhydrous benzene (100 mL) was boiled under reflux with 
azetropic removal of water for 6 hours and then concentrated to 20 mL. 
Tetrabutylammonium fluoride monohydrate (3.638 g, 13.914 mmol), 4A 
molecular sieves (8.664 g) and p-methoxylbenzyl chloride (4 mL, 29.5 mmol) 
were then added and the mixture was kept at room temperature overnight. 
Column chromatography on silica gel (hexane-ethyl acetate, 3:2) gave 
compound 234 (2.7 g, 83%). 
Step B--Preparation of Methyl 3-O-(4-methoxybenzyl)-L-fucopyranoside 
(compound 235) 
Compound 234 (900 mg, 2.64 mmol) was treated with 0.06N methanolic sodium 
methoxide (12 mL) for 2 hours. It was then neutralized by Amberlite IR 120 
(H.sup.+), filtered and evaporated to give compound 235 (785 mg, 100%). 
Step C--Preparation of Methyl 
2,4-di-O-benzyl-3-O-(4-methoxybenzyl)-L-fucopyranoside (compound 236) 
Sodium hydride (480 mg, 50% in mineral oil, 10 mmol) was added in small 
portions to compound 235 (774 mg, 2.6 mmol) in DMF (6 mL) which was cooled 
in dry ice. After 0.5 hours, benzyl bromide (1.05 mL, 8.8 mmol) was added 
and the reaction mixture was allowed to reach room temperature and kept 
there for 1 hour. Methanol was added to destroy the remaining sodium 
hydride and it was then evaporated. The residue was S taken up in 
dichloromethane, filtered through Celite and the filtrate was washed with 
water. Evaporation then gave crude compound 236. 
Step D--Preparation of Methyl 2,4di-O-benzyl-L-fucopyranoside (compound 
237) 
A mixture of 236 (2.6 mmol) and CAN (2.85 g, 5.2 mmol) in 
acetonitrile-water (9:1, 12 mL) was kept at room temperature for 1.5 hours 
and dichloromethane was added. The organic layer was separated and washed 
with water. After evaporation of the solvent, the residue was applied to a 
column of silica gel (hexane-ethyl acetate, 3:1) to yield compound 237 
(670 mg, 72%, 2 steps). 
Step E--Preparation of Methyl 
2,4-di-O-benzyl-3-O-(methylthio)thiocarbonyl-L-fucopyranoside (compound 
238) 
Sodium hydride (428 mg, 60% in mineral oil, 10.7 mmol) and imidazole (10 
mg) were added to compound 237 (640 mg, 1.787 mmol) in THF (16 mL). The 
reaction mixture was heated at 50.degree. C. for 0.5 hours and carbon 
disulfide (12 mL) was added. In another 1 hour, methyl iodide (12 mL) was 
added. Heating was continued for 1 more hour and the mixture was then 
cooled to room temperature and methanol was added. Concentration followed 
by column chromatography (hexane-ethyl acetate, 4:1) gave compound 238 
(790 mg, 98%). 
Step F--Preparation of Methyl 2,4di-O-benzyl-3-O-methyl-L-fucopyranoside 
(compound 239) 
Compound 238 (780 mg, 1.738 mmol) in anhydrous toluene (20 mL) was heated 
at 80.degree. C. AIBN (330 mg, 2.02 mmol) was added followed by 
tributyltin hydride (7.2 mL, 26.7 mmol). Heating was continued for 2 hours 
and the mixture was then concentrated and chromatographed (hexane-ethyl 
acetate, 3:1) to give compound 239 (450 mg, 70%). 
Step G--Preparation of 2,4-Di-O-benzyl-3-O-methyl-L-fucopyranose (compound 
240) 
Compound 239 (520 mg, 1.395 mmol) in glacial acetic acid (11 mL) and 6N HCl 
(2.3 mL) was heated at 65.degree. C. for 1.5 hours and evaporated, 
co-evaporated with toluene. The crude product 240 was used in the next 
reaction without purification. 
Step H--Preparation of p-Chlorophenyl 
2,4-di-O-benzyl-3-O-methyl-.beta.-L-thiofucopyranoside (compound 241) 
A mixture of compound 240 (490 mg, 1.367 mmol), anhydrous NaOAc (160 mg) 
and acetic anhydride (3.8 mL) in 1,2-dichloroethane (5 mL) was heated at 
60.degree. C. for 3.5 hours and cooled to room temperature. Water was 
added and the organic layer was separated and washed with water and 
aqueous sodium bicarbonate. After concentration, the dried residue was 
dissolved in dichloromethane (10 mL) and the mixture was cooled at 
0.degree. C. p-Chlorothiophenol (237 mg, 1.639 mmol) was added followed by 
BF.sub.3 -ether (0.5 mL). The reaction mixture was allowed to reach room 
temperature and kept there for 1.5 hours. It was then poured into 
ice-NaHCO.sub.3 and extracted with dichloromethane. Column chromatography 
(hexane-ethyl acetate, 6:1) of the residue on evaporation gave compound 
241 (440 mg, 66%). 
Step I--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4-di-O-benzyl-3-O-methyl-.alpha.-L-fucopyran 
osyl)-4-O-2,3-di-O-benzoyl-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-2- 
deoxy-.beta.-D-glucopyranoside (compound 242) 
DMF (0.5 mL) and tetraethylammonium bromide (160 mg, 0.76 mmol) were added 
to a suspension of copper bromide (870 mg, 3.90 mmol) and 4A molecular 
sieves (1.5 g) in dichloromethane (1 mL). After stirring at room 
temperature for 0.5 hours, a solution of compound 208 (480 mg, 0.51 mmol) 
in dichloromethane (2 mL) was added followed by compound 241 (550 mg, 1.13 
mmol) in dichloromethane (2 mL). The mixture was then kept in the dark for 
1 day and pyridine (1 mL) was added. The system was filtered through 
Celite, concentrated and column chromatographed (hexane-acetone, 5:2) to 
give compound 242 (430 mg, 66%). 
Step J--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4-di-O-benzyl-3-O-methyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-gl 
ucopyranoside (compound 243) 
Compound 242 (420 mg, 0.328 mmol) was treated with 0.06N methanolic sodium 
methoxide (8 mL) for 16 hours. The reaction system was then neutralized by 
Amberlite IR 120 (H.sup.+), filtered and evaporated. Column chromatography 
of the residue (hexane-acetone, 1:1) provided compound 243 (315 mg, 90%). 
Step K--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-6-O-benzyl-3-O-(2,4di-O-benzyl-3-O-methyl-.alpha.-L-fucopyrano 
syl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.b 
eta.-D-glucopyranoside sodium salt (compound 244) 
Sulfur trioxide-pyridine complex (70 mg, 0.44 mmol) was added to compound 
243 (300 mg, 0.279 mmol) in pyridine (1.7 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature. Stirring was continued for 
1 more hour and methanol was added. After evaporation of the solvent, the 
residue was applied to a column of silica gel (methanol-dichloromethane, 
15:85, 0.2% pyridine). The product obtained was then passed through a 
column of Amberlite IR-120 Na.sup.+ (MeOH) to give compound 244 (296 mg, 
90%). 
Step L--Preparation of 8-Methoxycarbonyloctyl 
2-acetamido-2-deoxy-3-O-(3-O-methyl-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulf 
o-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside sodium salt (compound 
245) 
Compound 244 (212 mg, 0.18 mmol) and palladium on carbon (5%, 220 mg) in 
MeOH (6 mL) were hydrogenated for 2 hours and pyridine was then added. 
After filtration of the catalyst and evaporation of the solvent, the crude 
product was purified by chromatography on silica gel (a) ethyl 
acetate-methanol-aqueous ammonia, 70:30:3, (b) isopropanol-water-aqueous 
ammonia, 80:6:2, (c) dichloromethane-methanol-water, 70:30:3, 0.2% 
pyridine) and then a column of Bio-Rex.RTM. 70 (Na.sup.+ form) to provide 
for compound 245 (99 mg, 68%). 
Example 32 
Preparation of 
2-benzamido-2-deoxy-3-O-(4-deoxy-.alpha.-L-fucopyranosyl)-4-O-(3-O-sulfo-. 
beta.-D-galactopyranosyl)-.beta.-D-glucopyranosyl benzamide sodium salt 
(compound 256) 
The synthesis of compound 256 is illustrated in FIG. 16. 
Step A--Preparation of Compound 247 
DMF (0.85 mL) and tetraethylammonium bromide (240 mg, 1.14 mmol) were added 
to a suspension of copper bromide (1305 mg, 5.85 mmol) and 4A molecular 
sieves (1.7 g) in dichloromethane (1 mL). After stirring at room 
temperature for 0.5 hours, a solution of compound 246 (400 mg, 0.8 mmol) 
in dichloromethane (1.6 mL) was added followed by compound 207 (1100 mg, 
2.418 mmol) in dichloromethane (1.6 mL). The mixture was then kept in the 
dark for 6 hours and pyridine (1 mL) was added. The solution was filtered 
through Celite, concentrated and column chromatographed (hexane-acetone, 
3:1) to give compound 247 (629 mg, 97%). 
Step B--Preparation of Compound 248 
Diethyl ether saturated with HCl was added to a mixture of 247 (600 mg, 
0.741 mmol), sodium cyanoborohydride (900 mg, 14.322 mmol), a few crystals 
of methyl orange and 3A molecular sieves (0.5 g) in dry THF (10 mL) at 
0.degree. C. until the color of the indicator turned red. Then stirring 
was continued for 1.5 hours and the reaction mixture was neutralized with 
triethylamine and filtered. The filtrate was washed with water, aqueous 
sodium bicarbonate and concentrated. The residue was dissolved in 
dichloromethane-methanol (1:1, 6 mL) and deionized by Amberlite MB-1 (2 
g). Chromatography on silica gel (hexane-acetone, 5:2) yielded compound 
248 (460 mg, 77%). 
Step C--Preparation of Compound 250 
A mixture of compound 248 (400 mg, 0.492 mmol), compound 249 (432 mg, 0.981 
mmol) and 4A molecular sieves (1.4 g) was stirred at -20.degree. C. 
N-Iodosuccinimide (317 mg, 1.412 mmol) was added followed by TfOH (42 
.mu.L). Stirring was continued for 1 hour at -20.degree. C. and pyridine 
(1 mL) was added. After concentration of the reaction mixture, the residue 
was applied to a column of silica gel (hexane-ethyl acetate, 3:2) to 
provide for compound 250 (360 mg, 64%). 
Step D--Preparation of Compound 251 
Compound 250 (400 mg, 0.35 mmol) was treated with 0.06N methanolic sodium 
methoxide (3 mL) at 0.degree. C. for 2 hours. It was neutralized by 
Amberlite IR 120 (H.sup.+), filtered and evaporated. The crude product, 
compound 251, was used in the next reaction without further purification. 
Step E--Preparation of Compound 252 
p-Toluene sulfonic acid (20 mg) was added to a solution of compound 251 
(0.35 mmol) in acetonitrile (3 mL) followed by 
.alpha.,.alpha.-dimethoxytoluene (0.1 mL, 0.67 mmol). After 0.5 hours at 
room temperature, the reaction mixture was neutralized with triethylamine 
and concentrated. Chromatography of the residue (hexane-acetone, 1:1) gave 
compound 252 (250 mg, 67%, 2 steps). 
Step E--Preparation of Compound 253 
A solution of compound 252 (220 mg, 0.205 mmol) in methanol (6 mL) and 
hydrazine hydrate (1 mL) was refluxed overnight and evaporated, 
co-evaporated with toluene and then dried on vacuum. The crude product, 
compound 253, was used in the next reaction without any further 
purification. 
Step F--Preparation of Compound 254 
Compound 253 was dissolved in a mixture of methanol (6 mL) and saturated 
aqueous sodium bicarbonate (4 mL). Benzoyl chloride (0.25 mL) was added to 
this mixture at 0.degree. C. After 0.5 hours, dichloromethane was added 
and the organic layer was separated. The residue, after evaporation of the 
solvent, was chromatographed (methanol-dichloromethane, 5:95) to yield 
compound 254 (150 mg, 70%--2-steps). 
Step G--Preparation of Compound 255 
Sulfur trioxide-pyridine complex (40 mg, 0.251 mmol) was added to compound 
254 (150 mg, 0.143 mmol) in pyridine (1.5 mL) at 0.degree. C. The reaction 
mixture was allowed to reach room temperature and more sulfur 
trioxide-pyridine complex (20 mg) was added. Stirring was continued for 1 
more hour and methanol was added. After evaporation of the solvent, the 
residue was applied to a column of silica gel (methanol-dichloromethane, 
10:90, 15:85, 0.2% pyridine). The product obtained was then passed through 
a column of Amberlite IR-120 Na.sup.+ (MeOH) to give compound 255 (120 
mg, 73%). 
Step H--Preparation of Compound 256 
Compound 255 (100 mg, 0.087 mmol) and Pd-C (5%, 200 mg) in MeOH (4 mL) were 
hydrogenated for 3.5 hours and pyridine (1.5 mL) was then added. After 
filtration of the catalyst and evaporation of the solvent, the crude 
product was purified by chromatography on silica gel 
(dichloromethane-methanol-water, 75:25:2.5, 0.2% pyridine) and then a 
column of Bio-Rex.RTM. 70 (Na.sup.+ form) to provide for compound 256 (40 
mg, 60%). 
Example 33 
Preparation of phenyl alanine 
amido-2-fuc(C)-amido-4-O-(3-O-sulfo-.beta.-D-galactopyranosyl)-.beta.-D-gl 
ucopyranoside (compound 315) 
The synthesis of compound 315 is illustrated in FIGS. 17-19. 
Step A--Preparation of 
4,6-O-Benzylidene-2-deoxy-2-phthalimido-.beta.-D-glucopyranosyl azide 
(compound 303) 
To a solution of compound 301 (19.0 g, 41.3 mmol), was added 20 mL of a 
0.5N solution of sodium methoxide in methanol. The resulting mixture was 
stirred for 2 hours at room temperature and then neutralized with 
Amberlite IR-120 (H.sup.+) resin, filtered and evaporated to obtain 
compound 302 which was directly converted into its 4,6-O-benzylidene 
derivative by dissolving the crude mass in acetonitrile (260 mL) and 
.alpha.,.alpha.-dimethoxy-toluene (15.0 mL), followed by addition of 
p-toluenesulfonic acid (1.3 g) and stirring the mixture overnight at room 
temperature. Neutralize the reaction mixture with triethylamine and 
evaporate. The crude mass was purified by chromatography on silica gel 
column, using hexane-ethyl acetate (2:1) as eluent to provide for compound 
303 (14.5 g, 85.5%). 
Step B--Preparation of 
3-O-Benzyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-.beta.-D-glucopyranosyl 
azide (compound 304) 
Compound 303 (13.0 g, 30.9 mmol) was dissolved in toluene (110 mL) and 
benzyl bromide (7.3 mL, 2.0 eq.) and silver oxide (31.4 g, 5.0 eq.) were 
added and the reaction mixture stirred for 24 hours at room temperature. 
The reaction solution was filtered and the solvent evaporated. The residue 
was purified by chromatography on silica gel using hexane-ethyl acetate 
(4:1) as eluent to provide for compound 304 (11.9 g, 75%). 
Step C--Preparation of 
2,6-Di-O-benzyl-2-deoxy-2-phthalimido-.beta.-D-glucopyranosyl azide 
(compound 305) 
Compound 304 (9.9 g, 19.4 mmol) was dissolved in dry THF (150 mL) at room 
temperature. The reaction mixture was cooled to 0.degree. C. and molecular 
sieves were added (10 g, 3A). Sodium cyanoborohydride (12.2 g, 194.0 mmol) 
was then added along with a small amount of methyl orange (a few 
crystals). The reaction mixture was stirred for 15 minutes at 0.degree. C. 
and then an etheral solution of hydrochloric acid was added until the 
mixture was acidic (pH.about.3). The reaction mixture was stirred for 2 
hours at 0.degree. C. at which time all the starting material had been 
completely consumed and converted to the product. The reaction mixture was 
then diluted and filtered and the precipitate was washed thoroughly with 
dichloromethane (1.0 L). The combined filtrates were then washed 
sequentially with a saturated solution of sodium bicarbonate (3.times.1.0 
L) and water (3.times.1.0 L), dried over sodium sulfate, filtered and 
evaporated. The product was purified by chromatography on silica gel using 
hexane-ethyl acetate (2:1) as eluent to give compound 305 (5.2 g, 52%). 
Step D--Preparation of 
3,6-Di-O-benzyl-2-phthalimido-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-.beta.-D 
-galactopyranosyl)-.beta.-D-glucopyranosyl azide (compound 307) 
Monosaccharide acceptor compound 305 (2.0 g, 3.9 mmol) and imidate donor 
compound 306 (4.8 g, 9.7 mmol), disclosed in Srivastava et al..sup.23, 
were dissolved in a mixture of ether and dichloromethane (20 mL, 2:1) and 
stirred at -10.degree. C. for 15 minutes. Boron trifluoride ethereate 
(1.34 mL, 10.9 mmol) was added and the reaction mixture was stirred under 
nitrogen at -10.degree. C. for 1.5 hours. After completion, the reaction 
medium was diluted with dichloromethane (250 mL), filtered and washed 
successively with a saturated solution of sodium bicarbonate (2.times.250 
mL) and water (2.times.250 mL). Evaporation of the solvent gave a syrup 
which was purified by chromatography on silica gel column using 
hexane-ethyl acetate (2:1) as eluent to provide for compound 307 (1.9 g, 
58.4%). 
Step E--Preparation of 1-Benzamido 
3,6-Di-O-benzyl-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-.beta.-D-galacto 
pyranosyl)-2-deoxy-.beta.-D-glucopyranoside (compound 307b) 
3,6-Di-O-benzyl-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl)-.beta.-D-galacto 
pyranosyl)-2-deoxy-.beta.-D-glucopyranosyl azide, compound 307 (10.4 g, 
12.3 mmol), was dissolved in a mixture of pyridine:water:triethylamine 
(4:1:0.1). The mixture was cooled to 0.degree. C. over 10 minutes and then 
hydrogen sulfide was passed through the reaction mixture over 1 hour at 
0.degree. C. The color of the solution turned to brownish-yellow and tlc 
indicated that the reaction was complete. After a 30 minute nitrogen purge 
was employed to remove hydrogen sulfide and the solvent was evaporated and 
then co-evaporated with toluene (200 mL) twice to dryness. The residue was 
passed through a short silica gel column (70-230 mesh), using hexane:ethyl 
acetate (1:1) as the eluent to provide for compound 307a. 
Compound 307a was then dissolved in a mixture of dry dichloromethane (200 
mL) and pyridine (5 mL) and then benzoyl chloride (5 mL, 43 mmol) was 
added. The mixture was stirred for 10 minutes at room temperature. Tlc 
indicated that the reaction was complete. The reaction mixture was washed 
with water and dried over anhydrous sodium sulfate, and then the solvent 
evaporated. The crude product was then chromatographed on silica gel 
(230-400 mesh) using hexane:ethyl acetate (2:1) as the eluent to provide 
11 g of compound 307b (yield 96%). 
Step F--Preparation of 1-Benzamido 
2-amino-3,6-Di-O-benzyl-4O-(.beta.-D-galactopyranosyl)-2-deoxy-.beta.-D-gl 
ucopyranoside (compound 307c) 
3,6-Di-O-benzyl-2-phthalimido-4-O-(2,3,4,6-tetra-O-acetyl-.beta.-D-galactop 
yranosyl)-2-deoxy-.beta.-D-glucopyranosyl azide, compound 307a, (7.8 g, 
8.45 mmol) was dissolved in methanol (200 mL) and then hydrazine hydrate 
(5 mL) was added. The mixture was heated to reflux for 2 hours and, then, 
tlc indicated that the reaction was complete. The solvent was evaporated 
and then co-evaporated with toluene (200 mL) twice to dryness. The residue 
was passed through a short silica gel column (70-230 mesh), using 
dichloromethane: methanol (5:1) as the eluent to provide for 2.8 g of 
compound 307c as a white solid (yield 53%). 
Step G--Preparation of 
2-amino-2-deoxy-3,6-Di-O-benzyl-4-O-(.beta.-D-galactopyranosyl)-.beta.-D-g 
lucopyranosyl azide (compound 308) 
Compound 307 (11.5 g, 13.6 mmol) was dissolved in methanol (20 mL) and a 
solution of hydrazine hydrate (8 mL, 164.6 mmol) was added. The reaction 
mixture was refluxed for 15 hours and then the solvent was evaporated to 
dryness. The residue was purified by chromatography on silica gel column 
using dichloromethane-methanol (80:20) as eluent to yield compound 308 
(6.1 g, 82%). 
Step H--Preparation of 
3,6-di-O-benzyl-2-(2,3,4-tri-O-benzyl-Fuc(C)-amido)-4O-.beta.L-D-galactop 
yranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide (compound 310) 
To a solution of compound 308 (3.9 g, 7.0 mmol) in dichloromethane (60.0 
mL) at room temperature was added 2,3,4-tri-O-benzylfucose carboxylic 
acid, compound 309 (5.9 g, 12.3 mmol) and 
1-(3-dimethylaminopropyl)-3-ethyl-carbodiimidate hydrochloride (4.7 g, 
24.6 mmol). The reaction mixture was stirred for 2 hours at room 
temperature and then the solvent was evaporated. The residue was purified 
on silica gel column chromatography using dichloromethane-methanol (95:5) 
as eluent to obtain compound 310 (5.7 g, 80%). 
Step I--Preparation of 
3,6-Di-O-benzyl-2-(2,3,4tri-O-benzyl-fuc-(C)-amido)-4-O-4,6-O-benzylidene 
-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide (compound 
311) 
To a solution of compound 310 (7.8 g, 7.8 mmol) dissolved in anhydrous 
acetonitrile (200 mL) was added benzaldehyde dimethylacetal (15.0 mL) and 
a catalytic amount of p-toluene sulfonic acid (350 mg). The reaction 
mixture was stirred for 15 hours at room temperature and neutralized with 
triethylamine. After evaporation, the residue was chromatographed on 
silica gel column eluting with dichloromethane-methanol (97.5:2.5) to 
provide for compound 311 (5.5 g, 65%). 
Step J--Preparation of 1-phenylalanineamido 
3,6-di-O-benzyl-2-(2,3,4tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O-benzylidene- 
.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside (compound 313) 
Compound 311 (500 mg, 0.46 mmol) was dissolved in a mixture of 
isopropanol-water (9:1, 40 mL) and hydrogenated with Raney nickel (100 mg) 
under atmospheric pressure for 1.5 hours. The catalyst was filtered and 
the solvent evaporated to obtain compound 312 which was directly converted 
into its phenylalanine amido derivative by dissolving in dichloromethane 
(7.0 mL) and reacting with N-CBz-L-phenylalanine (500 mg, 1.67 mmol) and 
EDC-HCl (500 mg, 2.6 mmol) for 0.5 hours. The solvent was evaporated and 
the residue chromatographed on silica gel using chloroform-ethyl acetate 
(2:3) as eluent to obtain compound 313 (426 mg, 69%). 
Step K--Preparation of 1-phenylalanineamido 
3,6-di-O-benzyl-2-(2,3,4-tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O-benzylidene 
-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 314) 
Compound 313 (362 mg, 0.27 mmol) was added to pyridine (6.0 mL) at 
0.degree. C. SO.sub.3 -pyridine complex (64 mg, 0.4 mmol) was added and 
stirring was continued for 0.5 hours at 0.degree. C. and 2 hours at room 
temperature. An additional amount of SO.sub.3 -pyridine complex (0.5 eq) 
was added and the mixture stirred for 3.5 hours and quenched with methanol 
(1.5 mL) and evaporated to dryness. The residue was chromatographed on a 
silica gel column eluting with dichloromethane-methanol-pyridine 
(95:5:0.1) to provide compound 314 (321 mg, 82.4%) after conversion to its 
sodium salt by passage through Dowex-50-X-8 (Na.sup.+) resin. 
Step L--Preparation of 1-phenylalanine 
amido-2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-.beta.-D- 
glucopyranoside sodium salt (compound 315) 
A mixture of compound 314 (321 mg, 0.22 mmol) and 5% palladium on carbon 
(330 mg) in methanol (30.0 mL) was stirred under one atmosphere of 
hydrogen for 5 hours. The mixture was then filtered through a pad of a 
Celite to remove the catalyst and the catalyst-Celite was washed with 
methanol (100 mL). The filtrate and washings were combined and evaporated 
after adding a trace of pyridine (5.0 mL). The resulting product was 
chromatographed on Iatrobeads eluting with isopropanol-water-ammonia 
(7:1.5:0.3) to provide compound 315 (70 mg, 41%) after conversion to the 
sodium salt by passage through Dowex-50-X-8 (Na.sup.+) resin. 
Example 34 
Preparation of 1-cyclohexylalanine 
amido-2-N-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-.beta.- 
D-glucopyranoside sodium salt (compound 316) 
The synthesis of compound 316 is illustrated in FIG. 19. 
Compound 314 (320 mg, 0.22 mmol) was hydrogenated in methanol (30 mL) using 
20% Pa(OH).sub.2 /C (1.5 g) for 4 days as described earlier to provide for 
compound 316 (17.0 mg, 10%) after purification by chromatography on silica 
gel using isopropanol-water-ammonia (7:1.5:0.5) as eluent and converting 
to sodium salt by passage through Dowex-50-X-8 (Na.sup.+) resin. 
Example 35 
Preparation of 
1-tryptophanamido-2-(fuc(C)-amido)-4-O-(3-O-sulfo-.beta.-D-galactopyranosy 
l)-.beta.-D-glucopyranoside (compound 319) 
The synthesis of compound 319 is illustrated in FIG. 20. 
Step A--Preparation of 
1-tryptophanamido-2-(2,3,4-tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O-benzylide 
ne-.beta.-D-galactopyranosyl!-2-deoxy-3,6-di-O-benzyl-.beta.-D-glucopyranos 
ide (compound 317). 
Compound 311 (500 mg, 0.46 mmol) was dissolved in a mixture of 
isopropanol-water (9:1, 50 mL) and hydrogenated with Raney nickel (100 mg) 
under atmospheric pressure for 45 minutes. The catalyst was filtered and 
the solvent evaporated to dryness. The residue without purification was 
dissolved in dichloromethane (7.0 mL) and reacted with EDC-HCl (500 mg, 
2.61 mmol) and Z-2-tryptophan for 1 hour. The reaction mixture was 
evaporated and the residue chromatographed on a silica gel column using 
dichloromethane-methanol (98:2) as eluent to provide for compound 317 (378 
mg, 60%) after sodium exchange. 
Step B--Preparation of 
1-tryptophanamido-2-(2,3,4-tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O-benzylide 
ne-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-3,6-di-O-benzyl-.beta.-D-gl 
ucopyranoside sodium salt (compound 318) 
Compound 317 (378 mg, 0.27 mmol) was dissolved in pyridine (6.0 mL) and to 
this mixture was added SO.sub.3 -pyridine complex (66 mg, 0.42 mmol) at 
0.degree. C. and reaction mixture was allowed to warm to room temperature. 
After 1 hour, another portion of SO.sub.3 -pyridine complex (0.5 eq) was 
added and addition was continued at the same rate at every 1.5, 2.5 and 3 
hours until all the starting material was completely converted into 
product. The reaction was quenched by the addition of methanol. 
Evaporation and co-evaporation provided a syrup which was purified by 
chromatography on silica gel column using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent to provide for pure 
compound 318 (260 mg, 64%) after sodium exchange. 
Step C--Preparation of 
1-tryptophanamido-2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosy 
l!-.beta.-D-glucopyranoside sodium salt (compound 319) 
Compound 318 (260 mg, 0.17 mmol) was hydrogenated for 6 hours in methanol 
(0.25 mL) and 5% palladium on carbon (750 mg) using hydrochloric acid (1.2 
eq) to provide for compound 319 (40 mg, 28%) after purification with 
chromatography on silica gel using isopropanol-water-ammonia (7:1.5:0.5) 
as eluent followed by its conversion into sodium salt. 
Example 36 
Preparation of 
1-acetamido-2-(fuc(C)-amido-4-O-3-O-sulfo-.beta.-D-galactopyranosyl)-2-de 
oxy-.beta.-D-glucopyranoside (compound 322) 
The synthesis of compound 322 is illustrated in FIGS. 18-21. 
Step A--Preparation of 1-thiophenyl 
acetamido-2-(2,3,4tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O-benzylidene-.beta. 
-D-galactopyranosyl!-2-deoxy-3,6-di-O-benzyl-.beta.-D-glucopyranoside 
(compound 320) 
Compound 311 (400 mg, 0.37 mmol) was dissolved in a mixture of 
pyridine-water-triethylamine (13:2:0.4). Hydrogen sulfide gas was bubbled 
through the solution at 0.degree. C. for 1 hour and then allowed to warm 
to room temperature for 1.5 hours. Evaporation of the mixture provided 
crude amine which was dissolved in pyridine (8.0 mL) and then 
(phenylthio)acetylchloride (117 .mu.L, 0.79 mmol) was added at 0.degree. 
C. and the resulting mixture stirred for 0.5 hours at room temperature 
before evaporation and chromatography of the residue on silica gel using 
dichloromethane-methanol (98:2) as eluent to provide compound 320 (177.6 
mg, 40%). 
Step B--Preparation of 1-thiophenyl 
acetamido-2-(2,3,4-tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O-benzylidene-3-O-s 
ulfo-.beta.-D-galactopyranosyl!-2-deoxy-3,6-di-O-benzyl-.beta.-D-glucopyran 
oside sodium salt (compound 321) 
Compound 320 (177.6 mg, 0.15 mmol) was dissolved in pyridine (4 mL) and 
cooled to 0.degree. C. SO.sub.3 -pyridine complex (40 mg, 0.25 mmol) was 
added to the reaction mixture and then the reaction mixture was allowed to 
warm to room temperature. An additional amount of SO.sub.3 -pyridine 
complex (2 eq, 0.5 eq. portions after every 0.5 hours) was added and the 
mixture stirred for 4 hours at room temperature. After addition of 
methanol (2 mL), the solvent was evaporated and the residue was 
chromatographed on a silica gel column using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent to obtain compound 
321 (172.3 mg, 90% after sodium exchange column). 
Step C--Preparation of 
1-acetamido-2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl)-2-d 
eoxy-.beta.-D-glucopyranoside (compound 322) 
Compound 321 (172.8 mg, 0.13 mmol) was hydrogenated under atmospheric 
pressure using methanol (30 mL) and 20% Pd(OH).sub.2 /C (200 mg) as 
described earlier to provide compound 322 (23.2 mg, 16%) after 
chromatography on silica gel using isopropanol-water-ammonia (7:1.5:0.5) 
as eluent followed by Na.sup.+ ion exchange column. 
Example 37 
Preparation of 1-Benzamido 
2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!)-2-deoxy-.beta. 
-D-glucopyranoside (compound 326) 
The synthesis of compound 326 is illustrated in FIGS. 21 and 22. 
Step A--Preparation of 1-Benzamido 
3,6-di-O-benzyl-2-(2,3,4-tri-O-benzyl-fuc(C)-amido)-4-O-3-D-galactopyrano 
syl!-2-deoxy-.beta.-D-glucopyranoside (compound 323). 
Compound 307c (325 mg, 0.52 mmol) was dissolved in dichloromethane (6.0 mL) 
and tri-O-benzyl-fucose-(C)-carboxylic acid (495 mg, 1.04 mmol) and 
EDC-HCl (398 mg, 2.1 mmol) were added thereto. The resulting mixture was 
stirred for 1 hour at room temperature. The solvent was evaporated and the 
residue chromatographed on silica gel using dichloromethane-methanol 
(95:5) as eluent to provide compound 323 (508 mg, 90%). 
Step B--Preparation of 
1-Benzamido-3,6-di-O-benzyl-2-(2,3,4-tri-O-benzyl-fuc(C)-amido)-4-O-4,6-O 
-benzylidene-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
(compound 324) 
Compound 323 (508 mg, 0.47 mmol) was dissolved in dry acetonitrile (15.0 
mL) and .alpha.,.alpha.-dimethoxytoluene (1.0 mL) was added thereto 
followed by p-toluene sulfonic acid (20.0 mg) and the reaction mixture was 
stirred for 45 minutes at room temperature, neutralized with triethylamine 
and the solvent evaporated. The residue was purified by chromatography on 
silica gel using dichloromethane-methanol (97.5:2.5) as eluent to provide 
compound 24 (298 mg, 54.2%). 
Step C--Preparation of 1-Benzamido 
3,6-di-O-benzyl-2-(2,3,4-tri-O-benzyI-fuc(C)-amido)-40-4,6-O-benzylidene- 
3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside 
(compound 325). 
Compound 324 (298 mg, 0.25 mmol) was dissolved in pyridine (5.0 mL) and 
cooled to 0.degree. C. SO.sub.3 -pyridine complex (61 mg, 0.38 mmol) was 
added to the reaction mixture and the reaction mixture was then allowed to 
warm to room temperature. After 1 hour, SO.sub.3 -pyridine complex (1.0 
eq) was again added and the reaction mixture stirred for 2 hours at room 
temperature. Methanol (2.0 mL) was added and the solvent was evaporated to 
dryness. The residue was purified by chromatography on silica gel using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent to provide for 
compound 325 (228 mg, 70.4%). 
Step D--Preparation of 
1-benzamido-2-(fuc(C)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyranosyl!-2-d 
eoxy-.beta.-D-glucopyranoside sodium salt (compound 326). 
Compound 325 (228 mg, 0.18 mmol) was dissolved in methanol (25 mL) and 
hydrogenated with 5% palladium on carbon (250 mg) as described earlier to 
provide for compound 326 (105 mg, 80%) after conversion to its sodium 
salt. 
Example 38 
reparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.varies.-L-fucopyranosyl)-4-O-3-O 
-sulfo-.beta.-D-galactopyranosyl!-6-O-sulfo-.beta.-D-glucopyranoside 
(compound 335) 
The synthesis of compound 335 is illustrated in FIGS. 22 and 23. 
Step A--Preparation of 
8-methoxyearbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-2-deoxy-.beta.-D-glucopyranoside (compound 328) 
Compound 327 (10.0 g), disclosed in Srivastava, et al..sup.23, was 
dissolved in a mixture of acetic acid-water (4:1, 100 mL) and heated to 
40.degree. C. for 15 hours. Only 50% reaction was complete. The reaction 
mixture was stirred for an additional 3 hours at 55.degree. C. and the 
solvent was was evaporated to dryness. The residue was redissolved in 
dichloromethane (150 mL) and washed with water (2.times.250 mL), 6% sodium 
hydrogen carbonate (2.times.250 mL) and water (2.times.250 mL), dried over 
sodium sulfate, filtered and the solvent evaporated. The syrup was 
purified by chromatography on silica gel using dichloromethane-methanol 
(9:1) as eluent to provide for compound 328 quantitatively. 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-6-O-mesyl-3-O-(2,3,4-tri-O-benzyl-.vari 
es.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside (compound 329) 
Compound 328 (10.0 g, 12.377 mmol) was dissolved in pyridine (90 mL) and 
mesyl chloride (1.14 mL, 14.8 mmol) was dropwise added thereto at 
0.degree. C. Stirring was continued for 2 hours at this temperature. 
Afterwards, the solvent was removed and the residue was chromatographed on 
a silica gel column using dichloromethane-methanol (97.5:2.5) as eluent to 
provide for compound 329 (10.05 g, 91.6%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-6-O-benzoyl-3-O-(2,3,4-tri-O-benzyl-.va 
ries.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside (compound 330) 
Compound 329 (1.0 g, 1.129 mmol) was dissolved in DMF (20.0 mL). Sodium 
benzoate (0.81 mg, 5.6 mmol) was added thereto and the resulting mixture 
stirred at 100.degree. C. for 24 hours by which time there was a complete 
consumption of starting material. After evaporation of the solvent, the 
residue was chromatographed on silica gel column using hexane-ethyl 
acetate (3:2) as eluent to provide for compound 330 (650 mg, 59%). 
S Step D--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-6O-benzoyl-3-O-(2,3,4tri-O-benzyl 
.varies.-L-fucopyranosyl)-4O-2,3-di-O-benzoyl-4,6-dichloro-4,6dideoxy-.be 
ta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside (compound 332) 
To a solution of compound 330 (605 mg, 0.663 mmol) in a mixture of 
dichloromethane-ether (1:2, 5.0 mL) stirred under nitrogen, was added 
dichloro dibenzoyl imidate (905 mg, 1.6 mmol) and the resulting mixture 
was cooled to -10.degree. C. to -15.degree. C. BF.sub.3 -ethereate 
solution (200 14L, 1.63 mmol) was added dropwise and stirring was 
continued for 1 hour at -10.degree. C. The reaction mixture was then 
diluted with dichloromethane and washed with water saturated NaHCO.sub.3 
solution and water. The resulting solution was dried over anhydrous sodium 
sulfate and evaporated. The residue was chromatographed on a silica gel 
column, eluting with hexane-ethyl acetate (2:1) as eluent to provide 
compound 332, 485 mg (55.6%). 
Step E--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-4-O-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-2-deoxy-.be 
ta.-D-glucopyranoside (compound 333) 
To a solution of compound 332 (485 mg, 0.372 mmol) in dry methanol (20.0 
mL) was added sodium methoxide (5 mL, 0.5M) solution in methanol and the 
resulting solution was stirred at room temperature for 5 hours. The 
mixture was then neutralized with resin, filtered and evaporated to 
dryness to provide for compound 333 (340 mg, 91.8%) after purification by 
chromatography on silica gel using dichloromethane-methanol (95:5) as 
eluent. 
Step F--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-2,3,4tri-O-benzyl-.varies.-L-fucop 
yranosyl!-4-O-4,6-dichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2- 
deoxy-6-O-sulfo-.beta.-D-glucopyranoside sodium salt (compound 334) 
To a solution of compound 333 (340 mg, 0.338 mmol) in pyridine (5.0 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (248 mg, 1.56 mmol). The 
sulfonation reaction was stirred at room temperature for 3 hours and 
methanol was added before evaporation and co-evaporation with toluene 
(3.times.20 TL). The residue was purified by chromatography on silica gel 
using dichloromethane-methanol-pyridine (93:7:0.1) as eluent to provide 
for compound 334 (320 mg, 78%) after sodium column. 
Step G--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.varies.-L-fucopyranosyl)-4-O-3-O 
-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-6-O-sulfo-.beta.-D-glucopyranosid 
e disodium salt (compound 335). 
Disulfo trisaccharide 334 (320 mg, 0.264 mmol) was hydrogenated over 
palladium on carbon (350 mg) in methanol (20.0 mL) as described earlier to 
provide for compound 335 (194 mg, 79%) after conversion to its sodium 
salt. 
Example 39 
Preparation 8-methoxycarbonyloctyl 
2-acetamido-3-O-.alpha.-L-fucopyranosyl!-4-O-4,6-dichloro-dideoxy-3-O-su 
lfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyrano 
side (compound 341) 
The synthesis of compound 341 is illustrated in FIG. 24. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-6-azido-2,6-dideoxy-.beta.-D-glucopyranoside (compound 336) 
Compound 329 (1.0 g, 1.13 mmol) was dissolved in dry DMF (10.0 mL) and 
sodium azide (550 mg, 7.7 mmol) was added thereto. The resulting solution 
was heated at 80.degree. C. under nitrogen for 3 days by which time most 
of the starting material was completely converted into product. The 
solvent was evaporated and the residue dissolved in dichloromethane (25.0 
mL). The organic layer was washed with water (2.times.25 mL), dried over 
Na.sub.2 SO.sub.4 and evaporated to give a yellow solid which was purified 
by chromatography on silica gel using hexane-ethyl acetate-methanol 
(1:1:0.05) as eluent to provide for compound 336 (657 mg, 70.0%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-4-O-2,3-di-O-benzoyl-4,6-dichloro-dideoxy-.beta.-D-galactopyran 
osyl!-6-azido-2,6-dideoxy-.beta.-D-glucopyranoside (compound 337) 
Compound 336 (2.73 g, 3.28 mmol) as a glycosyl acceptor and dichloro 
dibenzoyl imidate (4.67 g, 8.20 mmol) were dissolved in a mixture of 
dichloromethane-ether (40 mL, 1:1) and stirred at 0.degree. C. for 0.5 
hours. A solution of BF.sub.3 -ethereate (1.1 mL, 8.9 mmol) was added 
dropwise at this temperature and the reaction was then stirred overnight 
at 0.degree. C. The reaction solution was then diluted with 
dichloromethane (150 mL) and worked successively with water (2.times.150 
mL), 6% solution of sodium hydrogen carbonate (2.times.50 mL) and water 
(2.times.150 mL), dried over sodium sulfate, filtered and the solvent 
evaporated to dryness. The residue was purified by chromatography on 
silica gel using hexane-ethyl acetate (2:1) as eluent to yield compound 
337 (1.68 g, 43%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-4-O-2,3-di-O-benzoyl-4,6-dichloro-dideoxy-.beta.-D-galactopyran 
osyl!-6-amino-2,6-dideoxy-.beta.-D-glucopyranoside (compound 338). 
Compound 337 (1.68 g, 1.35 mmol) was dissolved in a mixture of 
pyridine-water-triethylamine (13:2:0.4) and a stream of hydrogen sulfide 
gas was bubbled at 0.degree. C. for 1 hour. The reaction mixture was then 
stirred for 15 hours at room temperature. Solvents were evaporated and the 
residue, compound 338, was used directly without further purification. The 
yield of compound 338 was quantitative at this stage. 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-4-O-2,3-di-O-benzoyl-4,6-dichloro-dideoxy-.beta.-D-galactopyran 
osyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyranoside (compound 338a) 
The crude amine, compound 338--obtained from Step C above, was dissolved in 
methanol (20 mL) and then a 6% solution of NaHCO.sub.3 (29 mL) was added 
followed by addition of benzoyl chloride (0.62 mL, 5.3 mmol). The reaction 
mixture was stirred for 1 hour at room temperature and then the solvent 
was evaporated. The residue was dissolved in dichloromethane (100 mL) and 
washed with water (2.times.100 mL), dried over Na.sub.2 SO.sub.4 before 
evaporation to a syrup which was purified by chromatography on silica gel 
using dichloromethane:methanol (98:2) as eluent to provide for compound 
338a (1.11 g, 62% based on the azido compound). 
Step E--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-4-O-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-6-benzamido 
-2,6-dideoxy-.beta.-D-glucopyranoside (compound 339) 
Compound 338a (501 mg, 0.38 mmol) was dissolved in methanol (20.0 mL) and a 
solution of sodium methoxide in methanol (5.0 mL, 0.5M) Was added thereto. 
The reaction mixture was stirred for 3 hours. The reaction mixture was 
then neutralized with Amberlite IR-120 (H.sup.+) resin, filtered and 
evaporated. The crude product was purified by chromatography on silica gel 
using dichloromethane:methanol (98:2) as eluent to provide for compound 
339 (357 mg, 84.6%). 
Step F--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.varies.-L-fuco 
pyranosyl)-4O-4,6-dichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6- 
benzamido-2,6-dideoxy-.beta.-D-glucopyranoside sodium salt (compound 340) 
Compound 339 (357 mg, 0.32 mmol) was dissolved in pyridine (6.0 mL) and 
SO.sub.3 -pyridine complex (284 mg, 1.77 mmol) was added thereto at 
0.degree. C. The reaction mixture was stirred for 0.5 hours at this 
temperature and 5.5 hours at room temperature. Afterwards, methanol (2.0 
mL) was added and the reaction mixture evaporated and the residue purified 
by chromatography on silica gel using dichloromethane-methanol-pyridine 
(95:5:0.1) as eluent to provide for compound 340 (333 mg, 85.4%, after 
sodium exchange resin). 
Step G--Preparation 8-methoxycarbonyloctyl 
2-acetamido-3-O-.alpha.-L-fucopyranosyl!-4-O-4,6-dichloro-dideoxy-3-O-su 
lfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyrano 
side sodium salt (compound 341) 
Hydrogenation of compound 340 (333 mg, 0.27 mmol) for 1 hour in methanol 
(20.0 mL) using 5% palladium on carbon (340 mg) as a catalyst provided for 
compound 341 (207 mg, 80%) after workup (as described above) and 
purification on Iatrobeads using dichloromethane-methanol-water-pyridine 
(80:20:2:0.1) as eluent followed by sodium exchange to effect conversion 
to the sodium salt. 
Example 40 
Preparation 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta. 
-D-glucopyranoside (compound 345) 
The synthesis of compound 345 is illustrated in FIG. 25. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-40-2,3-dibenzoyl-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-benzam 
ido-2,6-dideoxy-.beta.-D-glucopyranoside (compound 342) 
Compound 338a (6.5 mg, 4.93 mmol) was dissolved in toluene (30.0 mL) and 
tributyltin hydride (2.76 mL) and AIBN (30.0 mg) were added thereto. The 
reaction solution was then heated to reflux (90.degree. C.) for 5 hours by 
which time the reaction was complete. The solvent was evaporated and the 
residue was chromatographed on silica gel using hexane-ethyl acetate as 
the eluant (3:2, 1:1) to provide for compound 342 (4.8 mg, 78%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideo 
xy-.beta.-D-glucopyranoside (compound 343) 
Compound 342 (396 mg, 0.32 mmol) was dissolved in methanol (10.0 mL) and 
sodium methoxide in methanol (5.0 mL, 0.5M) was added thereto. The 
reaction mixture was stirred for 4 hours at room temperature. After 
neutralization with Amberlite IR-120 (H.sup.+) resin, filtration and 
evaporation, the material was purified by chromatography on silica gel 
using dichloromethane-methanol (95:5) as eluent to provide for compound 
343 (322 mg, 97.6%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dideoxy-3-sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2 
,6-dideoxy-.beta.-D-glucopyranoside sodium salt (compound 344) 
Compound 343 (266 mg, 0.26 mmol) was dissolved in pyridine (5.0 mL) and 
SO.sub.3 -pyridine complex (183 mg, 1.15 mmol) was added thereto at 
0.degree. C. The reaction mixture was stirred for 0.5 hours at 0.degree. 
C. and 4 hours at room temperature. After addition of methanol (2.0 mL), 
the reaction mixture was evaporated and the residue was purified by 
chromatography on silica gel using dichloromethane-methanol (95:5) as 
eluent to provide for compound 344 as the sodium salt (245 mg, 84% after 
sodium exchange resin). 
Step D--Preparation of 
8-methoxycarbonyloatyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dideoxy-3-sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D 
-glucopyranoside (compound 345) 
A solution of compound 344 (315 mg, 0.28 mmol) in methanol (30.0 mL) 
containing 5% palladium on carbon (315 mg) as a catalyst was hydrogenated 
at room temperature for 1.5 hours as described above to provide for 
compound 345 (188 mg, 78%) after purification by chromatography on silica 
gel using dichloromethane-methanol-water-pyridine (80:20:2:0.1) as eluent 
and conversion into the sodium salt by passage through Dowex 50-X-8 
(Na.sup.+) sodium exchange resin. 
Example 41 
Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-6-amino-2,6-dideoxy-.beta.-D-glucopyranosi 
de (compound 349) 
The synthesis of compound 349 is illustrated in FIGS. 25 and 26. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-(.beta.-D-galactopyranosyl!-6-azido-2,6-dideoxy-.beta.-D-gluc 
opyranoside (compound 346) 
A solution of compound 336 (600 mg, 0.72 mmol) and 2,3,4,6-tetraacetyl 
galactose-imidate, compound 306a, (709.47 mg, 1.44 mmol) in 
ether-dichloromethane (3:2) was cooled to -5.degree. C. and BF3Et.sub.2 O 
solution (265 .mu.L, 2.16 mmol) was added dropwise. The resulting reaction 
solution was stirred for 1.5 hours at this temperature. Then sodium 
hydrogen carbonate (1.6 g) was added and the resulting solution stirred 
for 10 minutes. A solution of sodium methoxide in methanol (3.0 mL, 1.0M) 
was then added and the system stirred. After 1 hour, an additional amount 
of 1M NaOMe/MeOH (2 mL) was added. The reaction mixture was then 
neutralized by addition of IR-120 (H.sup.+) resin (2.0 g) to adjust the pH 
to 6.0. The system was then filtered to remove the resin, the solvent 
evaporated, and the residue redissolved in ethyl acetate. The organic 
layer was washed with water (2.times.100 mL), dried over Na.sub.2 
SO.sub.4, filtered and evaporated to provide for compound 346 which was 
purified by chromatography on silica gel using dichloromethane-methanol 
(95:5) as eluent to provide for 392 mg (54.7%) of this compound. 
Step B--Preparation of 8-methoxycarbonyloctyl 
2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-4-O-4,6-O-be 
nzylidene-.beta.-D-galactopyranosyl!-6-azido-2,6-dideoxy-.beta.-D-glucopyra 
noside (compound 347) 
A solution of compound 346 (350 mg, 0.35 mmol) was dissolved in dry 
acetonitrile (5 mL). .alpha.,.alpha.-Dimethoxytoluene (79.3 .mu.L, 0.53 
mmol) and p-toluene sulfonic acid (10 mg) was added and the reaction 
mixture was stirred at room temperature for 5 hours. The mixture was then 
neutralized with triethylamine and the solvent evaporated. The residue was 
chromatographed on silica gel eluting with dichloromethane-methanol (98:2) 
as eluent to provide compound 347 (300 mg, 78.7%). 
Step C--Preparation of 8-methoxycarbonyloctyl 
2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-4-O-4,6-O-be 
nzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6 
azido-2,6-dideoxy-.beta.-D-glucopyranoside sodium salt (compound 348). 
To a solution of compound 347 (280 mg, 0.26 mmol) in pyridine (5 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (61.6 mg, 0.39 mmol). 
The reaction mixture was allowed to warm to room temperature and 
additional SO.sub.3 -pyridine complex was added after 0.5 hours (0.5 eq) 
and 1 hour (0.5 eq). The reaction was terminated after 2 hours by adding 
methanol and the solvents were then evaporated. The residue was 
chromatographed on a silica gel column, eluting with 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent, to provide for 
compound 348 (220 mg, 72%) after passage through Dowex-50-X-8 (Na.sup.+) 
ion exchange resin. 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-6-amino-2,6-dideoxy-.beta.-D-glucopyranosi 
de sodium salt (compound 349) 
A solution of compound 348 (220 mg, 0.19 mmol) was hydrogenated in methanol 
(6 mL containing 1.5 eq. of HCl) using 5% palladium on carbon (220 mg) for 
5 hours at atmospheric pressure. The solution was then filtered and the 
solvent evaporated. The residue was purified by chromatography on 
Iatrobeads using isopropanol-water-ammonia (7:1.5:0.5) an eluent to 
provide for compound 349 (120 mg, 80.7%) after conversion to its sodium 
salt by passage through Dowex-50-X-8 (Na.sup.+) ion exchange resin. 
Example 42 
Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyra 
noside (compound 353) 
The synthesis of compound 353 is illustrated in FIGS. 26 and 27. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopy 
ranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-benzamido-2,6- 
dideoxy-.beta.-D-glucopyranoside (compound 351) 
Compound 347 (250 mg, 0.23 mmol) was dissolved in a mixture of pyridine, 
triethylamine and water (2:0.5:0.05, 5 mL) and hydrogen sulfide was 
bubbled through the solution at 0.degree. C. for 2 hours and then at room 
temperature for 15 hours. The solvent was evaporated and co-evaporated 
with toluene to provide a residue, compound 350, which was converted into 
its benzamido derivative by reacting it with benzoyl choride (250 L) in a 
mixture of methanol-saturated sodium hydrogen carbonate (3:1). The product 
was evaporated dissolved in dichloromethane (50 mL) washed with water 
(2.times.50 mL), dried over Na.sub.2 SO.sub.4, filtered and evaporated to 
dryness. The residue was purified by chromatography on silica gel column 
using dichloromethane-methanol (98:2) as eluent, to provide for compound 
351 (220 mg, 82%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6-ben 
zamido-2,6-dideoxy-.beta.-D-glucopyranoside (compound 352). 
To a solution of compound 351 (220 mg, 0.20 mmol) in pyridine (5 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (45.2 mg, 0.28 mmol). 
The reaction mixture was allowed to warm to room temperature and 
additional SO.sub.3 -pyridine complex (22.1 mg, 0.14 mmol) was added and 
stirring was continued for 5 hours at room temperature by which time all 
the starting material was completely converted into product. The reaction 
mixture was quenched with methanol (2 mL) and evaporated to dryness. The 
residue was purified by chromatography on silica gel using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluant to provide for 
compound 352 (190 mg, 79.3%) as a sodium salt by passage through 
Dowex-50-X-8 (Na.sup.+) resin. 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-6-benzamido-2,6-dideoxy-.beta.-D-glucopyra 
noside (compound 353) 
Compound 352 (190 mg, 0.15 mmol) was hydrogenated in methanol (5 mL) using 
5% palladium on carbon (200 mg) as described earlier to provide for 
compound 353 (110 mg, 80.8%) after sodium conversion to the sodium salt by 
passage through Dowex-50-X-8 (Na.sup.+) resin. 
Example 43 
Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-.alpha.-L-fucopyranosyl!-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-6-chloro-2,6-dideoxy-.beta.-D-glucopyranos 
ide (compound 358) 
The synthesis of compound 358 is illustrated in FIG. 27. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-6-chloro-2,6-dideoxy-.beta.-D-glucopyranoside (compound 354) 
Compound 329 (200 mg, 0.23 mmol) was dissolved in anhydrous acetonitrile (3 
mL) and tetrabutylammonium chloride (150 mg, 0.54 mmol) was added. The 
reaction mixture was heated at 80.degree. C. for 15 hours. The solvent was 
then evaporated and the residue dissolved in dichloromethane (50 mL). The 
organic layer was washed with a 6% solution of NaHCO.sub.3 (2.times.50 mL) 
and water (2.times.50 mL), dried over Na.sub.2 SO.sub.4 evaporated and the 
residue was purified by chromatography on silica gel using hexane-ethyl 
acetate (1:1) as the eluent to provide for compound 354 (150 mg, 80.4%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,6-tri-O-benzyl-.alpha.-L-fucop 
yranosyl!-4-O-.beta.-D-galactopyranosyl!-6-chloro-2,6-dideoxy-.beta.-D-glu 
copyranoside (compound 355) 
Compound 354 (150 mg, 0.18 mmol) and imidate donor compound 306 (178.8 mg, 
0.36 mmol), disclosed in Srivastava et al..sup.23, was dissolved in a 
mixture of ether-dichloromethane (3 mL, 3:2) and cooled to -10.degree. C. 
BF.sub.3 -Et2O complex (144 .mu.L, 0.54 mmol) was slowly added dropwise to 
the reaction mixture which was then stirred at -10.degree. C. for 1 hour. 
Solid sodium bicarbonate (1.0 g) was then added to the mixture which was 
stirred for 10 minutes. A solution of sodium methoxide in methanol (2.0 
mL, 1M) was then added and the system stirred for 1 hour at room 
temperature. The reaction mixture was then neutralized with IR-120 
(H.sup.+) resin, filtered, and the solvent evaporated. The residue was 
purified by chromatography on silica gel using dichloromethane-methanol 
(95:5) as eluent to provide compound 355 (98.5 mg, 54.9%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-6-chloro-2,6-di 
deoxy-.beta.-D-glucopyranoside (compound 356) 
A solution of compound 355 (98.5 mg, 0.1 mmol), 
.alpha.,.alpha.-dimethoxy-toluene (30 .mu.L, 0.2 mmol) and p-toluene 
sulfonic acid (10 mg) in 8 mL acetonitrile was stirred at room temperature 
for 5 hours. The mixture was then neutralized with triethylamine and the 
solvent evaporated. The residue was chromatographed on silica gel using 
dichloromethane-methanol (98:2) as eluent to provide for compound 356 (90 
mg, 84%). 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl!-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-6-chl 
oro-2,6-dideoxy-.beta.-D-glucopyranoside (compound 357) 
To a solution of compound 356 (90 mg, 0.084 mmol) in pyridine (2 mL) at 
0.degree. C. was added SO.sub.3 -pyridine complex (20 mg, 0.13 mmol) and 
the resulting reaction mixture was allowed to warm at room temperature. 
After stirring for 1 hour, tlc indicated that the starting material was 
not completely consumed so an additional amount of SO.sub.3 -pyridine 
complex (1 eq) was added and stirring was continued for 3 hours. The 
mixture was then quenched with methanol (2 mL) and evaporated to dryness. 
The residue was chromatographed on Iatrobeads, eluting with 
dichloromethane-methanol-pyridine (95:5:0.1), to provide for compound 357 
(82.5 mg, 83.7%). 
Step E--Preparation of 
8-methoxycarbonyloctyl-2-acetamido-3-O-.alpha.-L-fucopyranosyl!-4-O-3-O- 
sulfo-.beta.-D-galactopyranosyl!-6-chloro-2,6-dideoxy-.beta.-D-glucopyranos 
ide sodium salt (compound 358). 
Compound 357 (82.5 mg, 0.07 mmol) was dissolved in methanol (5 mL) and 
hydrogenated with 5% palladium on carbon (50 mg) as described above to 
provide for compound 358 (45 mg, 78.4%) as its sodium salt. 
Example 44 
Preparation of 
2-acetamido-3-O-.alpha.-L-fucopyranosyl!-4-O-4,6-dichloro-dideoxy-3-O-su 
lfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide 
(compound 361) 
The synthesis of compound 361 is illustrated in FIG. 28. 
Step A--Preparation of 
2-acetamido-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosyl)-4-O- 
2,3-di-O-benzoyl-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-6-O-p-met 
hoxybenzyl-2-deoxy-.beta.-D-glucopyranosyl azide (compound 358a) 
2-Acetamido-2-deoxy-3-O-2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosy 
l!-6-O-p-methoxybenzyl-.beta.-D-glucopyranosyl azide (compound 106 as 
described above) (2.95 g, 3.38 mmol) and 
2,3-dibenzoyl-4,6-dichlorogalactose imidate donor (2.5 g, 4.39 mmol) was 
dissolved in dichloromethane (30 mL) and the reaction mixture was 
maintained at -20.degree. C. to -10.degree. C. Boron trifluoride etherate 
(BF3-Et.sub.2 O) (0.52 mL, 1.25 eq) was added dropwise at this temperature 
and the resulting system was stirred for 3-5 hours. The reaction mixture 
was quenched by the addition of triethylamine. The solvent was evaporated 
and the residue was purified by chromatography on silica gel using 
hexane-ethyl acetate (55:45, 1:1) as eluent to provide for compound 358a 
(1.46 g, 34%). 
Step B--Preparation of 
2-acetamido-3-O-2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosyl)-4-O- 
4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzyl-2-deox 
y-.beta.-D-glucopyranosyl azide (compound 359) 
Compound 358a (493 mg, 0.39 mmol) was dissolved in methanol (10 mL) and 
sodium methoxide in methanol (0.4 mL, 0.5M) was added. The reaction 
mixture was stirred for 2 hours at room temperature. The reaction mixture 
was then neutralized with IR-120 (H.sup.+) resin, filtered, and the 
solvent evaporated. The residue was purified by chromatography on silica 
gel using dichloromethane-methanol (97.5:2.5) as eluent to provide for 
compound 359 (3419 mg, 77%). 
Step C--Preparation of 
2-acetamido-3-O-2,3,4-tri-O-p-methoxybenzyl!-4-O-4,6-dichloro-dideoxy-3- 
O-sulfo-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzyl-2-deoxy-.beta.-D-glu 
copyranosyl azide sodium salt (compound 360) 
Compound 359 (468 mg, 0.44 mmol) was dissolved in pyridine (5 mL) and 
SO.sub.3 -pyridine complex (139 mg, 0.87 mmol) was added at 0.degree. C. 
and the reaction system was allowed to warm to room temperature. An 
additional amount of SO.sub.3 -pyridine complex (69 mg, 1.0 eq) was added. 
The reaction mixture was then stirred at room temperature for 5 hours 
whereupon the reaction was quenched by addition of methanol (2 mL) and the 
solvent evaporated. The residue was purified by column chromatography 
using dichloromethane:methanol:pyridine (93:7:0.1) to provide for compound 
360 as a sodium salt (380 mg, 74%) after sodium exchange column. 
Step D--Preparation of 
2-acetamido-3-O-.alpha.-L-fucopyranosyl!-40-4,6-dichloro-dideoxy-3-O-sul 
fo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide sodium 
salt (compound 361) 
Compound 360 (335 mg, 0.29 mmol) was dissolved in a mixture of 
acetonitrile:water (9:1, 10 mL) and solid ceric ammonium nitrate (CAN) 
(895 mg, 1.63 mmol) was added to the reaction mixture. The reaction 
mixture was then stirred for 15 hours at 0.degree. C. and then for 6.5 
hours at room temperature. The solvent was evaporated after addition of 
pyridine (1.0 mL) and the residue was purified by chromatography on 
Iatrobeads using isopropanol:water:ammonia (90:7.5:2.5) as eluent to 
provide for compound 361 (129 mg) after purification using Bio-Gel-P-2 
resin and conversion to sodium salt. 
Example 45 
Preparation of 
2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dideoxy-3-O-sulfo-.beta 
.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide (compound 370) 
The synthesis of compound 362 is illustrated in FIG. 29. 
Step A--Preparation of 
methyl-2,3-di-O-benzoyl-4,6-dideoxy-.alpha.-D-galactopyranosyl (compound 
363) 
Compound 362 (9.3 g, 21.2 mmol) was prepared from the known 
.alpha.-methyl-galactopyranosyl by reacting it with benzaldehyde dimethyl 
acetal and p-toluene sulfonic acid followed by benzoylation with benzoyl 
chloride in pyridine and removal of 4,6-O-benzylidene ring. Conversion of 
the 4,6-dihydroxy to the corresponding 4,6-dichloro-derivative was 
accomplished by reaction with sulfuryl chloride in pyridine. 
The 4,6-dichloro derivative, compound 362, was converted to the 
corresponding 4,6-dideoxy derivative by reaction with tributyl tin hydride 
(100 mL, 37 mmol) and AIBN (100 mg) in toluene (400 mL) at 90.degree. C. 
for 5 hours to provide for compound 363 (5.86 g, 74.7%) after purification 
by silica gel chromatography using hexane:ethyl acetate (9:1) as eluent. 
Step B--Preparation of acetyl-2,3-di-O-benzoyl-4,6-dideoxy-galactopyranose 
(compound 364) 
Compound 363 (4.5 g, 12.1 mmol) was reacted with a mixture of acetic 
anhydride:sulfuric acid (98.5:1.5) and stirred for 0.5 hours at room 
temperature. The reaction mixture was then quenched by addition of sodium 
bicarbonate. Dichloromethane (300 mL) was added and the organic layer was 
washed with 6% solution of sodium bicarbonate (2.times.300 mL) and water 
(2.times.300 mL), dried over Na.sub.2 SO.sub.4, filtered and evaporated to 
obtain crude product 364 quantitatively which was used for the next 
reaction without further purification. 
Step C--Preparation of 2,3-di-O-benzoyl-4,6-dideoxy-galactopyranose 
(compound 365) 
Compound 364 from the previous reaction (.about.12.0 mmol) was dissolved in 
THF (40 mL) and benzylamine (2.0 mL, 18 mmol) was added. The reaction 
mixture was stirred for 15 hours at room temperature to provide for 
compound 365 (1.36 g). 
Step D--Preparation of 
.alpha.-(2,3-di-O-benzoyl-4,6-dideoxy-D-glucopyranosyl)-trichloroacetimida 
te (compound 366) 
Compound 365 (1.35 g, 3.8 mmol) was dissolved in dichloromethane (15 mL) 
and reacted with DBU (0.28 mL, 1.9 mmol) and trichloroacetonitrile (1.9 
mL, 19 mmol) at 0.degree. C. for 45 minutes to provide the desired product 
366 (1.3 g, 68.5%) after purification by chromatography on silica gel 
using hexane:ethyl acetate (25:15) as eluent. 
Step E--Preparation of 
2-acetamido-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosyl)-4-O- 
2,3-di-O-benzoyl-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzy 
l-2-deoxy-.beta.-D-glucopyranosyl azide (compound 367) 
Compound 106 (1.2 g, 1.38 mmol) and compound 366 (1.00 g, 2.0 mmol) were 
dissolved in a mixture of ether and dichloromethane (1:1, 15.0 mL) and 
stirred at -20.degree. C. for 0.5 hours. Boron trifluoride etherate (0.37 
mL, 3.0 mmol) was added and the reaction mixture was stirred under 
nitrogen for 1 hour at -20.degree. C. The reaction was quenched by the 
addition of triethylamine and the solvent evaporated. The residue was 
purified by chromatography on silica gel column using hexane:ethyl acetate 
(4:1) as eluent to provide the title compound 367 (1.20 g, 71.8%). 
Step F--Preparation of 
2-acetamido-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosyl)-4-O- 
4,6-di-deoxy-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzyl-2-deoxy-.beta. 
-D-glucopyranosyl azide (compound 368) 
Compound 367 (1.15 g, 0.95 mmol) was dissolved in methanol (10.0 mL) and 
deacylated by adding sodium methoxide in methanol (2 mL, 0.5M) and then 
stirring the reaction mixture for 15 hours at room temperature. After 
neutralization with Amberlite IR-120 (H.sup.+) resin, filtration and 
evaporation, the product 368 was obtained quantitatively which was used 
without further purification. 
Step G--Preparation of 
2-acetamido-3-O-(2,3,4-tri-O-p-methoxybenzyl-.alpha.-L-fucopyranosyl)-4-O- 
4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-p-methoxybenzyl-2-deo 
xy-.beta.-D-glucopyranosyl azide (compound 369) 
Compound 368 (900 mg, 0.9 mmol) was dissolved in pyridine (7 mL) and 
SO.sub.3 -pyridine complex (286 mg, 1.8 mmol) was added at 0.degree. C. 
The reaction was allowed to warm to room temperature and, after stirring 
the mixture for 1 hour, an additional amount of SO.sub.3 -pyridine complex 
(143 mg, 0.9 mmol) was added and stirred for 2 hours at room temperature. 
The reaction mixture was quenched by the addition of methanol (5.0 mL), 
the solvent was evaporated and the residue purified by chromatography on 
silica gel using dichloromethane:methanol:pyridine (95:5:0.1) as eluent to 
provide for compound 369 (800 mg, 80.7% based on compound 368). 
Step H--Preparation of 
2-acetamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dideoxy-3-O-sulfo-.beta 
.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosyl azide sodium salt 
(compound 370). 
Compound 369 (1.0 g, 0.90 mmol) was dissolved in acetonitrile:water (9:1, 
50 mL) mixture and solid ceric ammonium nitrate (CAN) (2.83 g) was added 
at 0.degree. C. and the reaction mixture was stirred for 3 hours at this 
temperature. Additional CAN (943 mg, 2 eq.) was added and stirring was 
continued for an additional 3.5 hours. After addition of pyridine (3.0 
mL), the mixture was evaporated and purified by chromatography on silica 
gel using dichloromethane:methanol:water:pyridine (75:25:2.5:0.1) as 
eluent to provide for compound 370 (110 mg) as a sodium salt after sodium 
exchange column. 
Example 46 
Preparation of 
2-benzamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galacto-pyranosyl!-.beta.-D-glucopyranosyl benzamide (compound 385) 
The synthesis of compound 385 is illustrated in FIGS. 30 and 31. 
Step A--Preparation of 
2-Deoxy-2-phthalimido-3,4,6-tri-O-acetyl-.beta.-D-glucopyranosyl amine 
(compound 371) 
Compound 301 (20 g, 43.4 mmol) was dissolved in methanol (100 mL) and was 
then hydrogenated with 5% palladium on carbon (10 g) for 3 hours. The 
catalyst was removed by filtration. The filtrate was evaporated and the 
residue was dried under vacuum to provide for compound 371 (18.2 g, 97%). 
Step B--Preparation of 
2-Deoxy-2-phthalimido-3,4,6-tri-O-acetyl-.beta.-D-glucopyranosyl benzamide 
(compound 372) 
A solution of compound 371 (18.2 g, 41.9 mmol) in dichloromethane (200 mL) 
and pyridine (5.2 mL) was cooled to 0.degree. C. and benzoyl chloride (7.5 
mL) was added. After 0.5 hours, methanol was added to quench excess 
benzoyl chloride. The reaction mixture was diluted with dichloromethane 
(500 mL) and washed successively with water (2.times.500 mL), 6% solution 
of sodium bicarbonate (2.times.500 mL), and water (2.times.500 mL), dried 
over sodium sulfate, filtered and the solvent evaporated. The product was 
crystallized by dissolving in hot ethyl acetate and cooling to room 
temperature to provide for compound 372 (17.3 g, 76.7%). 
Step C--Preparation of 2-Deoxy-2-phthalimido-.beta.-D-glucopyranosyl 
benzamide (compound 373) 
Compound 372 (17.0 g, 31.6 mmol) was treated with 0.5N sodium methoxide in 
methanol (400 mL) at 0.degree. C. while stirring the reaction mixture for 
3 hours. The reaction solution was neutralized with Amberlite IR-120 
(H.sup.+) resin to maintain pH .about.6. The resin was filtered and the 
solvent evaporated to provide for compound 373 (12.7 g, 97.6%). 
Step D--Preparation of 
4,6-O-Benzylidene-2-deoxy-2-phthalimido-.beta.-D-glucopyranosyl benzamide 
(compound 374) 
p-Toluene sulfonic acid (400 mg) was added to a solution of compound 373 
(16.0 g, 38.8 mmol) in acetonitrile (300 mL) followed by addition of 
.alpha.,.alpha.-dimethoxytoluene (8.7 mL, 1.5 eq). The resulting reaction 
solution was stirred for 5 hours at room temperature and then the solution 
was neutralized with triethylamine and the solvent evaporated to provide 
for compound 374 quantitatively. 
Step E--Preparation of 
4,6-O-Benzylidene-2-deoxy-2-phthalimido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L- 
fucopyranosyl)-.alpha.-D-glucopyranosyl benzamide (compound 376) 
Copper (II) bromide (2.23 g, 5 eq.) and pulverized 4A molecular sieve (2.0 
g) were added to a reaction flask. Dry dichloromethane (5 mL) was syringed 
into the flask followed by dry DMF (1.8 mL). Tetraethylammonium bromide 
(420 mg, 1 eq.) was added to the reaction flask and the greenish black 
mixture was stirred for 30 minutes. The acceptor 
4,6-O-benzylidene-2-deoxy-2-phthalimido-.beta.-D-glucosylbenzamide, 
compound 374 (1.0 g, 2.0 mmol), was added to the reaction mixture, 
followed by the p-chlorothiophenyl 
2,3,4-tri-O-benzyl-.alpha.-L-fucopyranoside, compound 375 (1.68 mg, 3.0 
mmol). The mixture was stirred for 5 hours at room temperature by which 
time all the starting material was completely converted into the product. 
The reaction mixture was diluted with dichloromethane (100 mL) and washed 
successively with saturated solution of EDTA (5.times.100 mL), 6% solution 
of sodium bicarbonate (5.times.100 mL) and water (5.times.100 mL) dried 
over Na.sub.2 SO.sub.4, filtered, and the solvent evaporated to provide a 
crude residue which was crystallized with isopropyl alcohol to provide for 
compound 376 (1.5 g, 82%). 
Step F--Preparation of 
6-O-Benzyl-2-deoxy-2-phthalimido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyr 
anosyl)-.beta.-D-glucopyranosyl benzamide (compound 377) 
Diethyl ether saturated with HCl was added to a mixture of compound 376 
(8.4 g, 9.2 mmol), sodium cyanoborohydride (8.6 g, 15.0 eq), a few 
crystals of methyl orange and 3A molecular sieves (8.4 g) in dry THF (120 
mL) at 0.degree. C. until the color of the indicator turned red. Stirring 
was continued for 2 hours at 0.degree. C. and then the reaction solution 
was neutralized with triethylamine. The reaction mixture was diluted with 
dichloromethane (150 mL), filtered and washed with 6% sodium bicarbonate 
(5.times.500 mL) and water (5.times.500 mL), dried over Na.sub.2 SO.sub.4, 
filtered and the solvent evaporated. The residue was purified by 
chromatography on silica gel with hexane-ethyl acetate (2:1) as eluent to 
provide for compound 377 (7.0 g, 83%). 
Step G--Preparation of 
1-Benzamido-6-O-benzyl-2-deoxy-2-phthalimido-3-O-(2,3,4-tri-O-benzyl-.alph 
a.-L-fucopyranosyl)-4-O-2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranosyl!- 
.beta.-D-glucopyranoside (compound 379). 
A mixture of compound 377 (2.36 g, 2.60 mmol), phenyl 
2,3,4,6-tetra-O-acetyl-.beta.-D-thiogalactopyranoside, compound 378 (2.33 
g, 5.2 mmol) and 4A molecular sieves (11.8 g) was stirred at -20.degree. 
C. in dichloromethane-ether (1:1, 40 mL). NIS (N-iodosuccinimide) (1.73 g, 
7.7 mmol) was added followed by triflic acid solution (0.24 mL). Stirring 
was continued for 2 hours at -20.degree. C. and triethylamine was then 
added to quench the reaction. After evaporation of the solvent, the 
residue was purified by chromatography on silica gel column using 
hexane-ethyl acetate (1:1) as the eluent to provide compound 379 (2.1 g, 
65.5%). 
Step H--Preparation of 
1-benzamido-6-O-benzyl-2-deoxy-2-phthalimido-3-O-(2,3,4-tri-O-benzyl-.alph 
a.-L-fucopyranosyl)-4-O-.beta.-D-galactopyranosyl!-.beta.-D-glucopyranosid 
e (compound 380). 
Compound 379 (2.1 g, 1.68 mmol) was treated with 0.05M sodium methoxide in 
methanol (20 mL) at 0.degree. C. for 4 hours. The reaction solution was 
then neutralized with Amberlite IR-120 (H.sup.+) resin. The reaction 
solution was then filtered and the solvent evaporated to provide for 
compound 380 (1.5 g, 83%). 
Step I--Preparation of 
1-Benzamido-6-O-benzyl-2-deoxy-2-phthalimido-3-O-(2,3,4-tri-O-benzyl-.alph 
a.-L-fucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-.beta 
.-D-glucopyranoside (compound 381) 
p-Toluene sulfonic acid (30 mg) was added to a solution of compound 380 
(600 mg, 0.56 mmol) in acetonitrile (50 mL) followed by addition of 
benzaldehyde dimethylacetal (600 .mu.L). After stirring for 2 hours at 
room temperature, the reaction mixture was neutralized with triethylamine 
and the solvent evaporated. The residue was purified by chromatography 
using hexane-ethyl acetate (1:1) an eluent to provide for compound 381 
(535 mg, 82.4%). 
Step J--Preparation of 
1-Benzamido-6-O-benzyl-2-amino-2-deoxy-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-f 
ucopyranosyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-.beta.-D-gl 
ucopyranoside (compound 382) 
Compound 381 (535 mg, 0.46 mmol) was dissolved in methanol (5.0 mL) and a 
solution of hydrazine hydrate (1.75 mL, 70 eq) was added. The reaction 
mixture was refluxed for 9 hours at 75.degree. C. followed by evaporation 
and co-evaporation with toluene (3.times.20 mL) to provide for compound 
382 quantatively. 
Step K--Preparation of 
2-benzamido-6-O-benzyl-2-deoxy-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-.beta.-D-glucopyran 
osyl benzamide (compound 383) 
Compound 382 (450 mg, 0.43 mmol) was dissolved in methanol (10 mL) and then 
there was added thereto a saturated solution of sodium bicarbonate (20 mL) 
followed by benzoyl chloride (450 .mu.L) at 0.degree. C. The reaction 
solution was stirred for 0.5 hours by which time most of the starting 
material was converted to the product. The reaction solution was diluted 
with dichloromethane (150 mL) and washed with ice cold 6% solution of 
sodium bicarbonate (2.times.150 mL) and water (2.times.150 mL) dried over 
Na.sub.2 SO.sub.4 filtered and the solvent evaporated. The residue was 
purified by chromatography on Iatrobeads using ethyl acetate as eluent to 
provide the product 383 (300 mg, 60.6%). 
Step L--Preparation of 
2-Benzamido-6-O-benzyl-2-deoxy-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galacto-pyranosyl!-.beta.-D 
-glucopyranosyl benzamide (compound 384) 
Sulfur trioxide-pyridine complex (62 mg, 0.39 mmol) was added to compound 
383 (300 mg, 0.26 mmol) in pyridine (3 mL) at 0.degree. C. The reaction 
mixture was allowed to warm to room temperature and more SO.sub.3 
-pyridine complex was added (1.5 eq). Stirring was continued for 3 hours 
and methanol (5 mL) was then added. After evaporation of the solvent, the 
residue was purified by chromatography on silica gel Iatrobeads using 
dichloromethane-methanol-pyridine (9:1:0.1) as eluent to provide compound 
384 (280 mg, 85.6%). 
Step M--Preparation of 
2-benzamido-2-deoxy-3-O-(.alpha.-L-fucopyranosyl)-4-O-3-O-sulfo-.beta.-D- 
galactopyranosyl!-.beta.-D-glucopyranosyl benzamide sodium salt (compound 
385) 
Compound 384 (280 mg, 0.22 mmol) was hydrogenated in methanol (20 mL) using 
5% palladium on carbon (1.5 g) as a catalyst as described above to provide 
for compound 385 (140 mg, 78%) as its sodium salt. 
Example 47 
Preparation of 
8-methoxycarbonyloctyl-2-amino-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dich 
loro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyr 
anoside (compound 390) 
The synthesis of this compound is illustrated in FIG. 31 and 32. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopyrano 
syl)-40-2,3-di-O-benzoyl-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl)-6 
-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 387). 
Compound 386 (3.0 g, 3.40 mmol) and imidate donor (5.81 g, 10.2 mmol) were 
dissolved in a mixture of ether-dichloromethane (33 mL, 2:1) and stirred 
at -10.degree. for 15 minutes. Boron trifluoride ethereate (2.3 mL) was 
added and the reaction mixture was stirred under nitrogen for 15 hours at 
0.degree. C. The reaction solution was diluted with dichloromethane (250 
mL) and washed with cold saturated NaHCO.sub.3 (2.times.250 mL) and cold 
water (2.times.250 mL), dried over Na.sub.2 SO.sub.4, filtered and the 
solvent evaporated to dryness. The residue was purified by chromatography 
on Iatrobeads using dichloromethane-methanol (99:1) as the eluent to 
provide for compound 387 (3.5 g, 80%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deo 
xy-.beta.-D-glucopyranoside (compound 388) 
Compound 387 (3.5 g, 2.71 mmol) was dissolved in methanol (100 mL) and a 
solution of sodium methoxide in methanol (10.0 mL, 0.5M) was added and the 
reaction mixture was stirred for 5 hours at room temperature. The reaction 
solution was neutralized with Amberlite IR-120 (H.sup.+) resin, filtered 
and the solvent evaporated to provide for compound 388 (2.3 g, 79%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-4-O-4,6-dichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-be 
nzyl-2-deoxy-.beta.-D-glucopyranoside (compound 389) 
Compound 388 (528 mg, 0.49 mmol) was dissolved in dry pyridine (3.0 mL) and 
SO.sub.3 -pyridine complex (117.78 mg, 0.74 mmol) was added at 0.degree. 
C. and the reaction mixture was stirred for 0.5 hours at 0.degree. C. and 
then for 9 hours at room temperature. An additional amount of SO.sub.3 
-pyridine complex (117.78 mg, 0.74 mmol) was added followed by stirring 
the mixture for 0.5 hours at room temperature. Afterwards, methanol (5.0 
mL) was added to the reaction solution and the solvent was evaporated and 
the residue purified by chromatography on Iatrobead using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent to provide for 
compound 389 (301 mg, 51%). 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-amido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6-dich 
loro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyr 
anoside sodium salt (compound 390) 
Compound 389 (301 mg, 0.25 mmol) was dissolved in methanol (16.0 mL) 
containing .01M HCl in methanol (2.2 mL) and hydrogenated with 5% 
palladium on carbon (500 mg) for 1 hour at atmospheric pressure to obtain 
the product 390 (150 mg, 76%) after purification on Iatrobeads using 
dichloromethane:methanol:water:pyridine (80:20:2:1) as eluent followed by 
conversion into sodium salt. 
Example 48 
Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-gluc 
opyranoside (compound 394) 
The synthesis of compound 394 is illustrated in FIG. 32. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-amino-3-O-(2,3,4tri-O-benzyl-.alpha.-L-fucopyrano 
syl)-4-O-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D- 
glucopyranoside (compound 391). 
Compound 388 (1.35 g, 1.25 mmol) was dissolved in a mixture of 
pyridine:water:triethylamine (6:1:0.2). A stream of hydrogen sulfide was 
bubbled through the solution at 0.degree. C. for 0.5 hours and then at 
room temperature for 15 hours. The mixture was evaporated and 
co-evaporated with toluene and purified by chromatography on silica gel 
using ethyl acetate:hexane (4:1) as eluent to provide for compound 391 
(800 mg, 61%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dichloro-dideoxy-.beta.-D-galactopyranosyl!-6-O-benzyl-2 
-deoxy-.beta.-D-glucopyranoside (compound 392) Compound 391 (800 mg, 0.76 
mmol) was dissolved in methanol (10 mL) and a 6% solution of NaHCO.sub.3 
(10 mL) was added followed by addition of benzoyl chloride (500 .mu.L) at 
0.degree. C. The reaction mixture was stirred for 0.5 hours at 0.degree. 
C. by which time most of the starting material was converted to the 
product. The reaction solution was diluted with dichloromethane (150 mL) 
and washed with water (2.times.150 mL), dried over Na.sub.2 SO.sub.4, 
filtered, evaporated and the residue was purified by chromatography on 
silica gel using ethyl acetate:hexane (4:1) as eluent to provide for 
compound 392 (690 mg, 79%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6- 
O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 393) 
Compound 392 (246 mg, 0.21 mmol) was dissolved in dry pyridine (3.0 mL) and 
SO.sub.3 -pyridine complex (50.9 mg, 0.32 mmol) was added thereto at 
0.degree. C. The reaction mixture was stirred at 0.degree. C. for 0.5 
hours then 1 hour at room temperature. An additional amount of SO.sub.3 
-pyridine complex (50.9 mg, 0.35 mmol) was added followed by stirring for 
2 hours at room temperature. The reaction mixture was evaporated after 
addition of methanol (2.0 mL) and the residue was purified by silica gel 
column chromatography using dichloromethane:methanol:pyridine (95:5:0.1) 
as eluent to provide for compound 393 (176 mg, 67%). 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dichloro-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-gluc 
opyranoside (compound 394) 
Compound 393 (176 mg, 0.14 mmol) was hydrogenated in methanol (20 mL) using 
5% palladium on carbon as the hydrogenation catalyst (352 mg) in the 
manner described above to provide for compound 394 (111.0 mg, 86%). 
Example 49 
Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.-L-fucopyranosyl)-4-O-4,6- 
dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosi 
de (compound 397) 
The synthesis of compound 397 is illustrated in FIG. 33. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dideoxy-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.b 
eta.-D-glucopyranoside (compound 395) 
Tributyltin hydride (1.88 mL) and AIBN (20 mg) were added to a mixture of 
compound 392 (401 mg, 0.35 mmol) in dry toluene (20 mL) and the resulting 
solution was refluxed for 5 hours at 90.degree. C. The solvent was 
evaporated and the residue purified by chromatography on Iatrobeads using 
hexane:ethyl acetate (1:1) as eluent to provide for compound 395 (340 mg, 
89%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucop 
yranosyl)-4-O-4,6-dideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-6-O-benzyl- 
2-deoxy-.beta.-D-glucopyranoside (compound 396) 
SO.sub.3 -pyridine complex (74.8 mg, 0.47 mmol) was added to a solution of 
compound 395 (340 mg, 0.33 mmol) in pyridine (3.0 mL) at 0.degree. C. The 
reaction mixture was stirred for 15 minutes at this temperature and then 
for 1 hour at room temperature. An additional amount of SO.sub.3 -pyridine 
complex (74.8 mg) was added followed by stirring for 1 hour at room 
temperature. The solvent was evaporated. After addition of methanol (2.0 
mL), the product was purified by chromatography on Iatrobeads using 
dichloromethane:methanol:pyridine as eluent (95:5:0.1) to provide for 
compound 396 (297 mg, 81%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-(.alpha.L-fucopyranosyl)-4-O-4,6-d 
ideoxy-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranosid 
e (compound 397) 
Compound 396 (297 mg, 0.25 mmol) was dissolved in methanol (20 mL) and 
hydrogenated with 5% palladium on carbon (600 mg) for 0.5 hours at room 
temperature in the manner described above to provide for compound 397 
(153.4 mg, 72%) as a sodium salt. 
Example 50 
Preparation of 
8-methoxycarbonyloctyl-2-amino-4-O-(.alpha.-L-fucopyranosyl)-3-O-3-O-sulf 
o-.beta.-D-galactopyranosyl!-2-deoxy-.beta.-D-glucopyranoside sodium salt 
(compound 404) 
The synthesis of this compound is illustrated in FIGS. 33 and 34. 
Step A--Preparation of 
azido-(2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranosyl)-4,6-O-benzylidene 
-2-deoxy-.beta.-D-glucopyranoside (compound 399). 
Compound 398 (10.8 g, 23.3 mmol), compound 306 (14.9 g, 30.3 mmol) and 
molecular sieves were added to 1,2-dichloroethane (10.0 mL) and the 
resulting mixture stirred for 1 hour at room temperature. The mixture was 
then cooled to -18.degree. C. and a solution of trimethylsilyltriflate 
(1.72 mL) in 1,2-dichloroethane (1.0 mL) was added and the resulting 
mixture stirred for 0.5 hours. Triethylamine was then added at -18.degree. 
C. to quench the reaction and the reaction solution diluted with 
dichloromethane (50 mL) and filtered. The solvent was evaporated and the 
residue purified by chromatography on Iatrobeads using toluene-ethyl 
acetate (6:1) as eluent to provide for compound 399 (15.0 g, 81%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-(2,3,4,6tetra-O-acetyl-.beta.-D-galacto 
pyranosyl)-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 399a) 
To a mixture of compound 399 (9.36 g, 11.79 mmol) in diethyl ether 
saturated with HCl was added at 0.degree. C. sodium cyanoborohydride (7.41 
g, 117.9 mmol), a few crystals of methyl orange and 3A molecular sieves 
(9.36 g) in dry THF (300 mL) until the color of the indicator turned red. 
The stirring was continued for 3 hours and the reaction mixture was then 
neutralized with triethylamine and filtered. The filtrate was washed with 
water (2.times.500 mL), aqueous sodium bicarbonate (2.times.500 mL) and 
water (2.times.500 mL), dried over Na.sub.2 SO.sub.4, filtered, 
evaporated. The residue was purified by chromatography on silica gel using 
hexane-ethyl acetate (2:1) as eluent to provide compound 399a (7.28 g, 
78%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-azido-4-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl)-3-O-2,3,4,6-tetra-O-acetyl-.beta.-D-galactopyranosyl!-6-O-benzyl-2-d 
eoxy-.beta.-D-glucopyranoside (compound 400) 
DMF (12.0 mL) and tetraethylammonium bromide (1.92 g, 9.15 mmol) were added 
to a suspension of copper bromide (18.40 g, 82.53 mmol) and 4A molecular 
sieves (14.56 g) in dichloromethane (30 mL). The reaction mixture was 
stirred at room temperature for 0.5 hours and then a solution of compound 
399a (7.28 g, 9.15 mmol) in dichloromethane (10.0 mL) and thioglycoside 
375 (25.67 g, 45.75 mmol) were added. The mixture was kept in the dark for 
15 hours and the reaction solution was diluted with dichloromethane (250 
mL). The molecular sieves were filtered and washed with dichloromethane 
(250 mL). The filtrate was washed successively with saturated EDTA 
solution (5.times.500 mL), 6% sodium bicarbonate solution (3.times.500 mL) 
and water (3.times.500 mL) dried over sodium sulfate, filtered, and the 
solvent evaporated. The residue was purified by chromatography on silica 
gel using hexane:ethyl acetate (3:1) as eluent to provide for compound 400 
(9.15 g, 83%) 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-azido-4-O-2,3,4-tri-O-benzyl-.alpha.-L-fucopyran 
osyl!-3-O-.beta.-D-galactopyranosyl!-6-O-benzyl-2-deoxy-.beta.-D-glucopyra 
noside (compound 401) 
Compound 400 (9.1 g, 7.51 mmol) was dissolved in methanol (50 mL) and a 
solution of sodium methoxide in methanol (10.0 mL, 0.5M) was added 
thereto. The reaction mixture was stirred for 5 hours at room temperature 
and the reaction solution was then neutralized with Amberlite IR-120 
(H.sup.+) resin, filtered and the solvent evaporated to provide for 
compound 401 (7.5 g, 96%). 
Step E--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-4,6-O-benzylidene-.beta.-D-galactopyra 
nosyl!-4-O-2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl!-6-O-benzyl-2-deoxy- 
.beta.-D-glucopyranose (compound 402) 
p-Toluene sulfonic acid (310 mg) was added to a solution of compound 401 
(7.2 g, 6.9 mmol) in acetonitrile (250 mL) followed by the addition of 
.alpha.,.alpha.-dimethoxytoluene (2.1 mL, 13.8 mmol). After stirring the 
reaction mixture for 5 hours at room temperature, it was neutralized with 
triethylamine and the solvent evaporated. The residue was purified by 
chromatography on silica gel using hexane-ethyl acetate (1:1) as eluent to 
provide for compound 402 (6.5 g, 83%). 
Step F--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-g 
alactopyranosyl!-4-O 
-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-6-O-benzyl-2-deoxy-.beta.-D- 
glucopyranoside (compound 403) 
Sulfur trioxide-pyridine complex (127.33 mg, 0.80 mmol) was added to a 
solution of compound 402 (600 mg, 0.53 mmol) in pyridine (5.0 mL) at 
0.degree. C. and the reaction mixture was stirred for 1 hour at room 
temperature. An additional amount of SO.sub.3 -pyridine (1.5 eq) complex 
was added and the reaction mixture stirred for 3 hours at room 
temperature. After addition of methanol (2.0 mL), the solvent was 
evaporated and the residue was purified by chromatography on Iatrobeads 
using dichloromethane-methanol-pyridine (95:5:0.1) as eluent to provide 
for compound 403 (420 mg, 64%). 
Step G--Preparation of 
8-methoxycarbonyloctyl-2-amino-3-O-3-O-sulfo-.beta.-D-galactopyranosyl!-4 
-O-(.alpha.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside sodium salt 
(compound 404) 
Compound 403 (350 mg, 0.28 mmol) and 5% palladium on carbon (700 mg) in 
methanol (20 mL) was hydrogenated as described above to provide for 
compound 404 (175 mg, 82%) after conversion to the sodium salt. 
Example 51 
Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-3-O-sulfo-.beta.-D-galactopyranosy 
l!-4-O-(.alpha.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside (compound 
408) 
The synthesis of compound 408 is illustrated in FIGS. 34 and 35. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-amino-3-O-4,6-O-benzylidene-.beta.-D-galactopyra 
nosyl!-4-O-(2,3,4-tri-O-benzyl-(.alpha.L-fucopyranosyl)-6-O-benzyl-2-deoxy- 
.beta.-D-glucopyranoside (compound 405) 
Compound 402 (750 mg, 0.66 mmol) was dissolved in a mixture of 
pyridine-water-triethylamine (4:1:0.1, 10 mL) at 0.degree. C. and hydrogen 
sulfide gas was passed through over 1 hour at 0.degree. C. and then 15 
hours at room temperature. The reaction mixture was evaporated and 
co-evaporated with toluene to provide 2-amino-derivative, compound 405, 
quantitatively. 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-4,6-O-benzylidene-.beta.-D-galacto 
pyranosyl!-4-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-6-O-benzamido-2 
-deoxy-.beta.-D-glucopyranoside (compound 406) 
Compound 405 (450 mg, 0.41 mmol) was dissolved in methanol (5.0 mL) and a 
saturated sodium hydrogen carbonate solution (2.0 mL) was added at 
0.degree. C. followed by addition of benzoyl chloride (225 .mu.L) and the 
reaction mixture was stirred for 1 hour at 0.degree. C. and then for 3 
hours at room temperature. The reaction solution was diluted with 
dichloromethane (100 mL), washed with water (2.times.100 mL), dried over 
Na.sub.2 SO.sub.4, filtered and evaporated. The residue was purified by 
chromatography on Iatrobeads using ethyl acetate-hexane (2:1) as eluent to 
provide for compound 406 (400 mg, 80%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-4,6-O-benzylidene-3-O-sulfo-.beta. 
-D-galactopyranosyl!-4-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-6-O-b 
enzyl-2-deoxy-.beta.-D-glucopyranoside sodium salt (compound 407) 
Compound 406 (350 mg, 0.29 mmol) was dissolved in pyridine (3.0 mL) and 
SO.sub.3 -pyridine complex (70 mg, 0.44 mmol) was added as a solid at 
0.degree. C. The reaction mixture was stirred for 0.5 hours at 0.degree. 
C. and 1 hour at room temperature. Further addition of SO.sub.3 -pyridine 
complex (1.0 eq) was made followed by stirring the mixture at room 
temperature for 3 hours. The solvent was evaporated after addition of 
methanol (2.0 mL) and purified by chromatography on Iatrobeads using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent to provide for 
compound 407 (285 mg, 76%) as a sodium salt by passage through 
Dowex-50-X-8 (Na.sup.+) column. 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-benzamido-3-O-3-O-sulfo-.beta.-D-galactopyranosy 
l!-4-O-(.alpha.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside sodium 
salt (compound 408). 
Compound 407 (250 mg, 0.19 mmol) was hydrogenated in methanol (10 mL) using 
5% palladium on carbon (250 mg) for 5 hours at atmospheric pressure and 
room temperature in the manner described above to provide for compound 408 
(155 mg, 95%) as a sodium salt. 
Example 52 
Preparation of 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-3-O-sulfo-.beta.-D-galactop 
yranosyl!-4-O-(.alpha.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside 
(compound 411) 
The synthesis of compound 411 is illustrated in FIG. 35. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-4,6-O-benzylidene-.beta.-D- 
galactopyranosyl!-4-O-(2,3,4-tri-O-benzyl-.alpha.-L-fucopyranosyl)-6-O-benz 
yl-2-deoxy-.beta.-D-glucopyranoside (409) 
Compound 405 (500 mg, 0.45 mmol) was dissolved in dichloromethane (10.0 mL) 
and 4-nitrobenzoic acid (500 mg) and 1-(3-dimethylaminopropyl)-3-ethyl 
carbodiimide hydrochloride (500 mg) were added thereto. The reaction 
mixture was stirred for 1 hour at room temperature. The solvent was then 
evaporated and the residue purified by chromatography on Iatrobeads using 
hexane-ethyl acetate (1:1) as eluent to provide for compound 409 (314 mg, 
56%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-4,6-O-benzylidene-3-O-sulfo 
-.beta.-D-galactopyranosyl!-4-O-(2,3,4tri-O-benzyl)-.alpha.-L-fucopyranosyl 
)-6-O-benzyl-2-deoxy-.beta.-D-glucopyranoside (compound 410) 
Compound 409 (314 mg, 0.25 mmol) was sulfated with SO.sub.3 -pyridine 
complex (118 mg) by dissolving in pyridine (3.0 mL) and stirring the 
reaction mixture at 0.degree. C. for 0.5 hours and then for 2 hours at 
room temperature. The reaction was quenched by the addition of methanol 
and the solvent evaporated. The residue was purified by chromatography on 
Iatrobeads using dichloromethane-methanol-pyridine (95:5:0.5) as the 
eluent to provide for compound 410 (275 mg, 80%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-p-nitrobenzamido-3-O-3-O-sulfo-.beta.-D-galactop 
yranosyl!-4-O-(.alpha.-L-fucopyranosyl)-2-deoxy-.beta.-D-glucopyranoside 
sodium salt (compound 411) 
Compound 410 (275 mg, 0.20 mmol) was hydrogenated in methanol (10 mL) using 
5% palladium on carbon (275 mg) as described above to provide for compound 
411 as a sodium salt (175 mg, 95%). 
Example 53 
Preparation of 
8-methoxycarbonyloctyl-2-(fuc(c)-amido)-4-O-3-O-sulfo-.beta.-D-galactopyr 
anosyl!-2-deoxy-.beta.-D-glucopyranoside (compound 423) 
The synthesis of compound 423 is illustrated in FIGS. 36 and 37. 
Step A--Preparation of 
8-methoxycarbonyloctyl-2-azido-2-deoxy-3-O-benzyl-4,6-O-benzylidene-.beta. 
-D-glucopyranoside (compound 413) 
To a stirred solution of compound 412 (2.5 g, 5.39 mmol) in dry toluene 
(15.0 mL) were added benzyl bromide (1.28 mL, 10.78 mmol) and freshly 
prepared silver oxide (2.5 g), and the reaction mixture was then stirred 
for 15 hours. At this point, reaction was not complete and an additional 
amount of silver oxide (2.5 g) was added and the reaction stirred for 2 
days. The reaction system was diluted with dichloromethane (100 mL) and 
the resulting solution was filtered through Celite and the residue was 
washed with dichloromethane. The solvent was evaporated and the residue 
purified by chromatography on silica gel using hexane-ethyl acetate (4:1) 
as eluent to provide for compound 413 (2.1 g, 70%). 
Step B--Preparation of 
8-methoxycarbonyloctyl-2-azido-2-deoxy-3-O-benzyl-.beta.-D-glucopyranoside 
(compound 414) 
Compound 413 (2.4 g, 4.33 mmol) was dissolved in 80% aqueous acetic acid 
(10.0 mL) and heated to 80.degree. C. for 3 hours. The mixture was 
evaporated and diluted with dichloromethane (50 mL) and washed 
successively with saturated NaHCO.sub.3 solution (2.times.5 mL), water 
(2.times.50 mL), dried over Na.sub.2 SO.sub.4, filtered, and the solvent 
evaporated. The residue was purified by chromatography on silica gel using 
hexane-ethyl acetate (1:1) as eluent to provide for compound 414 (1.6 g, 
79%). 
Step C--Preparation of 
8-methoxycarbonyloctyl-2-azido-2-deoxy-3-O-benzyl-6-O-tert-butyldimethylsi 
lyl-.beta.-D-glucopyranoside (compound 415) 
Compound 414 (1.6 g, 3.44 mmol) was dissolved in dry DMF (5.0 mL) and 
imidazole (0.5 g, 2.2 eq) and tert-butyldimethyl silyl chloride (775 mg, 
5.16 mmol) were added thereto. The reaction solution was stirred for 5 
hours at room temperature and was then diluted with dichloromethane (50 
mL) and washed successively with water (2.times.50 mL), 6% sodium 
bicarbonate (2.times.50 mL) and water (2.times.50 mL), dried over Na.sub.2 
SO.sub.4, filtered and evaporated to provide a residue which was purified 
by chromatography on silica gel using hexane-ethyl acetate (9:1) as eluent 
to provide for compound 415 (1.72 g, 86%). 
Step D--Preparation of 
8-methoxycarbonyloctyl-2-azido-3-O-benzyl-4-O-(4,6-O-benzylidene-2,3-di-O- 
benzoyl-.beta.-D-galactopyranosyl)-6-O-tert-butyl-dimethyl-silyl-.beta.-D-g 
lucopyranoside (compound 417) 
To a mixture of compound 415 (1.6 g, 2.7 mmol), galactosyl bromide 416 
(3.72 g, 6.90 mmol) and molecular sieves (3.2 g) in nitromethane-toluene 
(1:1, 10 mL) at 0.degree. C. was added dropwise a solution of 
2,6-dimethylaminopyridine (843 mg, 6.90 mmol) and silver triflate (1.77 g, 
6.90 mmol) in nitromethane-toluene (5.0 mL) and the resulting solution was 
allowed to room temperature after 1 hour. The reaction solution was then 
diluted with dichloromethane (50 mL) and washed with cold saturated 
solution of NaHCO.sub.3 (2.times.50 mL), water (2.times.50 mL), dried over 
Na.sub.2 SO.sub.4 filtered and the solvent co-evaporated to dryness. The 
residue was purified by chromatography on silica gel using hexane-ethyl 
acetate (9:1, 5:1) as eluent to provide product 417 (1.76 g, 62%). 
Step E--Preparation of 
8-methoxycarbonyloctyl-2-azido-2-deoxy-3,6-di-O-benzyl-4-O-(4,6-O-benzylid 
ene-2,3-di-O-benzoyl)-.beta.-D-glucopyranoside (compound 418) 
Compound 417 (1.76 g, 1.70 mmol) was treated with 80% aqueous acetic acid 
for 8 hours at room temperature. Evaporated and co-evaporated with toluene 
and the residue was purified by chromatography on silica gel using 
hexane-ethyl acetate (4:1) as eluent to provide for compound (418a) which 
was benzylated with benzyl bromide and silver oxide in toluene as 
described earlier to provide compound 418 (1.0 g, 58%). 
Step F--Preparation of 
8-methoxycarbonyloctyl-2-amino-2-deoxy-3,6-di-O-benzyl-4-O-(4,6-O-benzylid 
ene-2,3-di-O-benzoyl-.beta.-D-galactopyranosyl)-.beta.-D-glucopyranoside 
(compound 419) 
Compound 418 (1.0 g, 0.99 mmol) was dissolved in a mixture of 
pyridine:water:triethylamine (4:1:0.1) and cooled to 0.degree. C. Hydrogen 
sulfide gas was bubbled through the solution for 1 hour at 0.degree. C. 
and the reaction was stirred at room temperature for 15 hours before 
evaporation and co-evaporation of the mixture with toluene. The yield of 
compound 419 at this stage was quantitative. 
Step G--Preparation of 
8-methoxycarbonyloctyl-2-(2,3,4tri-O-benzyl-fuc(c)-amido)-3,6-di-O-benzyl- 
40-4,6-O-benzylidene-2,3-di-O-benzyl!-.beta.-D-galactopyranosyl-O-D-glucop 
yranoside (compound 420). 
To a solution of compound 419 (850 mg, 0.86 mmol) in dry dichloromethane 
(20 mL) was added 2,3,4-tri-O-benzyl-.alpha.-L-fucopyrano-sylacetic acid 
(compound 309) (819.7 mg, 1.72 mmol) and EDC (850 mg). The reaction 
mixture was stirred for 15 hours at room temperature and diluted with 
dichloromethane (100 mL). The mixture was washed with aqueous sodium 
bicarbonate (2.times.100 mL) and water (2.times.100 mL), dried over 
Na.sub.2 SO.sub.4, filtered and evaporated. The residue was then 
chromatographed on silica gel using hexane-ethyl acetate (2:1) as eluent 
to provide compound 420 (920 mg, 74%). 
Step H--Preparation of 
8-methoxycarbonyloctyl-2-(2,3,4tri-O-benzyl-fuc(c)-amido)-3,6-di-O-benzyl- 
40-4,6-O-benzylidene-.beta.-D-galactopyranosyl!-.beta.-D-glucopyranoside 
(compound 421) 
Compound 420 (920 mg, 0.64 mmol) was saponified in methanol (10 mL) using 
0.5N sodium methoxide in methanol (5.0 mL). After neutralization with 
Amberlite IR-120 (Na.sup.+) resin, filtration and evaporation of the 
solvent, the residue was purified by chromatography on silica gel using 
hexane-ethyl acetate (1:1) as eluent providing for compound 421 (750 mg, 
95%). 
Step I--Preparation of 
8-methoxycarbonyloctyl-2-(2,3,4-tri-O-benzyl-fuc(c)-amido-3,6-di-O-benzyl- 
4-O-4,6-O-benzylidene-3-O-sulfo-.beta.-D-galactopyranosyl!-2-deoxy-.beta.- 
D-glucopyranoside (compound 422) 
SO.sub.3 -pyridine complex (146.43 mg, 0.92 mmol) was added to a solution 
of compound 421 (750 mg, 0.61 mmol) in pyridine (5 mL) at 0.degree. C. and 
reaction was stirred for 0.5 hours at this temperature and 1 hour at room 
temperature. An additional amount of SO.sub.3 -pyridine complex (1.0 eq) 
was added and the reaction stirred for 3 hours at room temperature. 
Evaporated the mixture after addition of methanol and the residue was 
purified by chromatography on silica gel using 
dichloromethane-methanol-pyridine (95:5:0.1) as eluent providing compound 
422 (620 mg, 75%). 
Step J--Preparation of 
8-methoxycarbonyloctyl-2-(fuc(c)-amido)-4-O-3-O-sulfo-.beta.-D-galacto-py 
ranosyl!-2-deoxy-.beta.-D-glucopyranoside (compound 423) 
Compound 422 (350 mg, 0.26 mmol) was dissolved in methanol (10 mL) and 
hydrogenated with 5% palladium on carbon (350 mg) as described earlier to 
provide for compound 423 (175 mg, 85%) as a sodium salt. 
Example A 
Inhibition of DTH Inflammatory Response 
DTH inflammatory responses of representative oligosaccharide glycosides 
were measured using the mouse footpad swelling assay as described by Smith 
and Ziola.sup.2. Briefly, groups of Balb/c mice (about 19-20 grams each) 
were immunized with 100 .mu.g of the OVA antigen (Albumin, Chicken Egg, 
Sigma, St. Louis, Mo.) containing 20 .mu.g of the adjuvant 
(DDA--dimethyldioctadecyl-ammonium bromide, Eastman Kodak, Rochester, 
N.Y.) which also induces a strong inflammatory DTH response in PBS 
(phosphate buffer saline). 
Seven days later, each group of mice was footpad-challenged with 20 .mu.g 
of the OVA antigen (without adjuvant). 
To assess the effect of the oligosaccharide glycoside on the inflammatory 
DTH response, mice received 10 .mu.g or 100 .mu.g of the oligosaccharide 
glycoside to be tested five hours after challenge. Control groups were 
left untreated or received 100 .mu.L of phosphate-buffered saline (PBS). 
Any resulting inflammatory footpad swelling was measured with a Mitutoyo 
Engineering micrometer 24 hours after challenge. The amount of footpad 
swelling observed in mice treated with the oligosaccharide glycoside being 
tested was measured as a percentage reduction relative to the amount of 
swelling observed for the control. The results are set forth in Table I. 
TABLE I 
______________________________________ 
% REDUCTION 
COMPOUND.sup.1 
DOSE Trial 1 Trial 2 
Trial 3 
Average 
______________________________________ 
A. 100 .mu.g 
15 15 
-- 100 .mu.g 
25 25 
-- 100 .mu.g 
46 47.9 46.95 
-- 10 .mu.g 
46 46 
-- 10 .mu.g 
25.2 25.2 
-- 10 .mu.g 
52.7 42.5 50 48.4 
B 10 .mu.g 
27.1 27.1 
-- 100 .mu.g 
44.8 47 30.6 40.8 
C 100 .mu.g 
30.7 30.7 
C 10 .mu.g 
21.3 21.3 
-- 100 .mu.g 
28.5 28.5 
D 100 .mu.g 
46.2 46.2 
E 100 .mu.g 
45.7 45.7 
F 10 .mu.g 
44.2 44.2 
______________________________________ 
.sup.1 Compounds tested were: 
Compound A = 
8Methoxycarbonyloctyl-2-nitrobenzamido-4-O-(D-galactopyranosyl)-2-deoxy-D 
glucopyranose; 
Compound B = 
8Methoxycarbonyloctyl-4-O-(4-O-phospho-D-galactopyranosyl)-D-glucopyranos 
de disodium salt; 
Compound C = 
8Methoxycarbonyloctyl-2-acetamido-3-O-(L-fucopyranosyl)-4-O-3,4,6tri-O-s 
lfo-D-galactopyranosyl2-deoxy-D-glucopyranoside trisodium salt; and 
Compound D = 
8Methoxycarbonyloctyl-2-acetamido-3-O-(2,3,4-tri-O-benzyl-L-fucopyranosyl 
-4-O-3O-sulfo-2-O-(L-fucopyranosyl)-D-galactopyranosyl)-2-deoxy-D-glucopy 
anoside sodium salt. 
Compound E = 
8Methoxycarbonyloctyl-4-O-(4-O-sulfo-D-galactopyranosyl)-D-glucopyranbsid 
sodium salt; 
Compound F = 
8Methoxycarbonyloctyl-2-acetamido-3-O-(3,6-diphospho-.beta.)galactopyrano 
yl)-2-deoxy-D-glucopyranoside tetrasodium salt; 
The data in Table I demonstrate that the oligosaccharide glycosides 
represented by compounds A-F are effective in reducing antigen induced 
inflammation in a sensitized mammal. 
While the present invention has been described with reference to what are 
considered to be the preferred examples, it is to be understood that the 
invention is not limited to the disclosed examples.