Libraries are synthesized with oligomeric carbopeptoids and carbonucleotoids. Carbopeptides are oligosaccharides having carbohydrate subunits linked to one another by amide bonds. Carbonucleotoids are oligosaccharides having carbohydrate subunits linked to one another by phosphodiester bonds. Carbopeptide libraries may be fabricated using automated polypeptide synthesizers.

SPECIFICATION
 1. Field of the Invention
 The invention relates to oligosaccharides and libraries incorporating
 oligosaccharide. More particularly, the invention relates to
 oligosaccharides and libraries of oligosaccharides which employ amide
 and/or phosphodiester linkages for joining adjacent carbohydrate subunits.
 2. Background
 Carbohydrates are known to mediate many cellular recognition processes.
 Carbohydrates can serve directly as binding molecules and, in such
 instances, are essential to the recognition process. A review of the
 biological role of carbohydrates with respect to cellular recognition
 phenomena is provided by Sharon et al. (Scientific American, January 1993,
 82). The emerging importance to glycobiology is further characterized by
 Mekelburger et al. (Angew. Chem. Int. Ed. Engl. 1992, 31, 1571) and by
 Dagani et al. (Chem. Eng. News, Feb. 1, 1993, 28).
 Dysfunctional mediation of cellular recognition processes can lead to
 disease states. If a cellular recognition process is mediated by an
 oligosaccharide, then an absence or excess of such oligosaccharide can
 lead to a dysfunctional mediation of such process. The mediating
 oligosaccharide may be deficient or absent due to a deficiency of
 production or due to a high rate of catabolism. If rate of catabolism is
 excessive, then catabolically resistant analogs of the bioactive
 oligosaccharide may be preferred as drug candidates as compared to the
 native bioactive oligosaccharide.
 Accordingly, what is needed is a library which includes analogs of known
 bioactive oligosaccharides. Such a library may be usefully employed for
 screening drug candidates.
 Central requirements for the design of libraries of oligosaccharide analogs
 include the following:
 (a) A need to maximize the potential of the designed oligosaccharides as
 ligand and drug candidates;
 (b) A need to capitalize on existing highly sophisticated technology
 directed to the synthesis of oligopeptides and oligonucleotides in order
 to facilitate the rapid and efficient design and construction of
 oligosaccharides; and
 (c) A need for flexibility with respect to synthesizing either single
 target molecules or large libraries of target molecules simultaneously.
 Methodologies for synthesizing biopolymers are well developed for peptides,
 nucleic acids, and saccharides. Segments of oligopeptides and of
 oligonucleotides can now be routinely synthesized both in solution and in
 the solid phase, manually and/or on automated systems. The synthesis of
 such structures is facilitated by the availability of efficient techniques
 and sophisticated instrumentation for synthesizing peptide and phosphate
 bonds with high yields. The synthesis of oligopeptides and
 oligonucleotides is also facilitated by the absence of stereocenters in
 these linkages. In contrast, technology for the construction of
 oligosaccharides is comparatively less sophisticated and efficient.
 Synthetic methods for constructing oligosaccharides give comparatively
 lower yields and are complicated by the two isomer possibilities (.alpha.
 and .beta.) in glycoside bond formation.
 Techniques and chemical methods for simultaneously synthesizing multiple
 oligopeptides, e.g. 100-150 completely different peptides having lengths
 of up to 20 amino acid residues, are reviewed by Jung, G. et al. (Angew.
 Chem, Int. Ed. Engl. 1992, 31, 367-383--incorporated therein by
 reference). Such techniques facilitate the construction of oligopeptide
 libraries.
 Simon, et al. (Proc, Natl. Acad. Sci. USA, 1992, 89, 9367-9371) disclose
 oligopeptide analogs in which amino acid side chain groups are attached
 not to conventional peptide backbone carbons but to peptide backbone
 nitrogens. Such analogs are termed peptoids. Simon also discloses the
 construction of peptoid libraries as a modular approach to drug discovery.
 Simon's oligopeptoids are shown by calculation to have greater
 conformational freedom as compared to conventional oligopeptides.
 Accordingly, oligopeptoids are thought to have greater potential as
 pharmaceutically useful binding ligands as compared to conventional
 oligopeptides having close sequence homology to such oligopeptoids.
 Von Roedern et al. disclose a carbohydrate amino acid (Angew. Chem, Int.
 Ed. Engl. 1994, 31, 687-689). Although von Roedern discloses that
 carbohydrate amino acids may be coupled to peptides, he does not disclose
 that they may also be polymerized so as to form oligosaccharides.
 SUMMARY
 A first aspect of the invention involves the molecular design and chemical
 synthesis of a class of carbohydrates designated as carbopeptoids (CPD's).
 Glycopeptoids are preferred carbopeptoids. Carbopeptoids and glycopeptoids
 are oligosaccharides which employ peptide-like amide bonds for linking the
 various carbohydrate subunits within an oligomer assembly. Amide bond
 formation may be achieved by employing oligopeptide synthesis technology
 and instrumentation. The method allows for the design and synthesis of
 specific compounds for biological and pharmacological investigations. The
 method also allows for the generation of libraries of compounds for
 biological and pharmacological screening. Conventional screening
 techniques employed with respect to peptide and peptoid libraries (Simon
 et al., supra) may also be employed with respect to carbopeptoid
 libraries. The design takes advantage of the multifunctionality of
 carbohydrate subunits to maximize the binding properties of the molecules.
 The ease and high efficiency by which the peptide-like linkages can be
 constructed make the synthesis of these molecules a practical proposition.
 Furthermore, non-carbohydrate units may be inserted into the sequence
 making this approach even more flexible and versatile for the generation
 of new libraries of organic compounds.
 More particularly, the invention is directed to a oligomeric carbopeptoid
 or glycopeptoid compound having carbohydrate amino acid subunits (CA's) or
 glycoside amino acid subunits (GA's) coupled to one another via an amide
 linkage. The amide linkage may be represented by the formula CA.sub.1
 --(CO--NH)--CA.sub.2. The amide linkage (CO--NH) includes a carbonyl
 carbon and an amido nitrogen. A first carbohydrate amino acid subunit
 CA.sub.1 or glycoside amino acid subunit GA.sub.1 has an anomeric carbon
 bonded to the carbonyl carbon of the amide linkage. The anomeric carbon of
 the first carbohydrate amino acid subunit CA.sub.1 forms a C-glycosidic
 bond with the carbonyl carbon of the amide linkage and maintains the
 carbohydrate in a closed ring configuration. A second carbohydrate amino
 acid subunit CA.sub.2 has a non-anomeric carbon bonded to the amido
 nitrogen of the amide linkage. The second carbohydrate amino acid subunit
 CA.sub.2, like the first amino acid subunit CA.sub.1, may include an
 anomeric carbon bonded to the carbonyl carbon of a second amide linkage
 linking the second carbohydrate amino acid subunit CA.sub.2 to a third
 carbohydrate amino acid subunit CA.sub.3, etc. In this instance, the
 anomeric carbon of the second carbohydrate amino acid subunit CA.sub.2
 forms a C-glycosidic bond with the carbonyl carbon of the amide linkage
 and maintains the carbohydrate in a closed ring configuration. On the
 other hand, if the second carbohydrate amino acid subunit CA.sub.2 is a
 terminal subunit, then its anomeric carbon may form a hemiacetal, a
 hemiketal, or a glycoside.
 The invention is also directed to a process for synthesizing the above
 oligomeric carbopeptoid or glycopeptoid compound. The synthetic process
 involves the coupling of two or more carbohydrate amino acid subunits
 (CA's) or glycoside amino acid subunits (GA's) to one another by means of
 amide linkages.
 The invention is also directed to libraries of oligomeric carbopeptoid or
 glycopeptoid compounds. Such libraries are employable for drug screening.
 Each oligomeric carbopeptoid or glydopeptoid compound includes at least
 two carbohydrate amino acid subunits (CA's) or glycoside amino acid
 subunits (GA's) coupled to one another via an amide linkage as indicated
 above. The invention is also directed to an improved process for
 synthesizing the above library of oligomers. The process employs an
 elongation step for coupling the subunits to one another to produce the
 oligomers. In the elongation step, two carbohydrate amino acid subunits
 (CA's) or glycoside amino acid subunits (GA's) are coupled to one another
 via an amide linkage as indicated above.
 The invention is also directed to chemical intermediates for producing
 oligomeric carbopeptoids. A first chemical intermediate is a derived
 carbohydrate amino acid having an anomeric carbon and non-anomeric
 carbons. The anomeric carbon is substituted with a carboxyl radical. Each
 of the non-anomeric carbons is substituted with a radical selected from
 the group consisting of blocked hydroxyl, blocked amino, differentially
 protected amino, and hydrogen, with the proviso that at least one radical
 is a differentially protected amino. A second chemical intermediate is a
 derived carbohydrate amino acid similar to the first except that the
 non-anomeric carbons are substituted with a radical selected from the
 group consisting of blocked hydroxyl, blocked amino, unprotected amino,
 and hydrogen, with the proviso that at least one radical is an unprotected
 amino and at least one radical is a blocked hydroxyl or amino.
 A second aspect of the invention involves the molecular design and chemical
 synthesis of a class of carbohydrates designated as carbonucleotoids
 (CND's). Carbonucleotoids are oligosaccharides which employ
 oligonucleotide-like phosphate bonds for linking the various carbohydrate
 subunits within an oligomer assembly. Phosphate bond formation may be
 achieved by employing technology and instrumentation developed for
 oligonucleotide synthesis. The phosphate bonds employed within
 carbonucleotoids are convenient linkages for coupling these units. The
 ease and high efficiency by which the oligonucleotide-like linkages can be
 constructed make the synthesis of these molecules a practical proposition.
 The disclosed methods are characterized by their versatility and
 practicality. The methods may exploit conventional solid phase and
 automated synthesis techniques for producing carbopeptoids and
 carbonucleotoids in large scale.
 More particularly, the second aspect of the invention is directed to an
 oligomeric carbonucleotoid molecule comprising carbohydrate C-glycoside
 subunits (CG's) coupled to one another via a phosphodiester linkage. The
 phosphodiester linkage may be represented by the structure: CG.sub.1
 -C.sub.1 '--(O--PO(OH)--O)-CG.sub.2. The first carbohydrate C-glycoside
 subunit (CG.sub.1 -C.sub.1 ') has an anomeric carbon forming a
 C-glycosidic bond with a carbon C.sub.1 '. In turn the carbon C.sub.1 ' is
 bonded to the phosphodiester linkage. The second carbohydrate C-glycoside
 subunit CG.sub.2 has a non-anomeric carbon bonded to the phosphodiester
 linkage. The invention is also directed a process for synthesizing the
 oligomeric carbonucleotoid molecule. The process employs a coupling step
 wherein two or more carbohydrate C-glycoside subunits (CG's) are coupled
 by means of a phosphodiester linkage as indicated above.
 The second aspect of the invention is also directed to libraries of
 oligomeric carbonucleotoid molecules. The libraries are employable for
 drug screening. Each oligomeric carbonucleotoid molecule including at
 least two carbohydrate C-glycoside subunits (CG's) coupled to one another
 by means of a phosphodiester linkage as indicated above. The invention is
 also directed to an improved process for synthesizing a library of
 oligomers. The process employs an elongation step wherein subunits are
 coupled to one another to produce the oligomers. The improvement is
 directed to the use of phosphodiester linkage linkages for linking the
 C-glycoside subunits as indicated above.
 The second aspect of the invention is also directed to derived carbohydrate
 C-glycosides having an anomeric carbon and non-anomeric carbons. The
 anomeric carbon forms a C-glycosidic bond with carbon C.sub.1 '. In turn,
 the carbon C.sub.1 ' is bonded to an phosphoramidite. Each of the
 non-anomeric carbons is substituted with a radical selected from the group
 consisting of blocked hydroxyl, differentially protected hydroxyl, and
 hydrogen, with the proviso that at least one radical is a differentially
 protected hydroxyl. An alternative derived carbohydrate C-glycoside is
 similar to the above except that each of the non-anomeric carbons is
 substituted with a radical selected from the group consisting of blocked
 hydroxyl, unprotected hydroxyl, and hydrogen, with the proviso that at
 least one radical is an unprotected hydroxyl and at least one radical is a
 blocked hydroxyl.
 ##STR1##

DETAILED DESCRIPTION
 Retrosynthetic schemes for carbopeptoids (compound I) and carbonucleotoids
 (compound II) are illustrated in Scheme 1.
 The carbopeptoids (CPD's) are oligomers having repeating carbohydrate
 subunits linked to one another by means of amide linkage units. More
 particularly, the carbonyl carbon of each amide linkage unit is bonded to
 the anomeric carbon of a carbohydrate subunit. Similarly, the amide
 nitrogen of the amide linkage unit is bonded to a non-anomeric carbon. The
 retrosynthetic scheme suggests that the amide bond may be split and that
 the preferred starting materials are carbohydrate amino acids.
 Carbonucleotoids (CND's) are oligosaccharides in which carbohydrate
 C-glycoside subunits (CG's) are linked to one another by means of
 phosphodiester bonds. More particularly, the retrosynthetic scheme
 suggests that the phosphate group may be eliminated, yielding hydroxylated
 starting material.
 Scheme 2 illustrates representative carbohydrate amino acid subunits (CA's)
 and carbohydrate C-glycoside subunits (CG's). Preferred carbohydrate amino
 acid subunits (CA's) include the following:
 D-glucose having an unprotected carboxyl at the anomeric C(1) position, an
 unprotected amino group at the C(6) position, and blocked hydroxyls at the
 C(2), C(3), and C(4) positions;
 D-mannose having an unprotected carboxyl at the anomeric C(1) position, an
 unprotected amino group at the C(6) position, and blocked hydroxyls at the
 C(2), C(3), and C(4) positions;
 D-galactose having an unprotected carboxyl at the anomeric C(1) position,
 an unprotected amino group at the C(6) position, and blocked hydroxyls at
 the C(2), C(3), and C(4) positions;
 ##STR2##
 N-acetyl-D-glucosamine having an unprotected carboxyl at the anomeric C(1)
 position, an unprotected amino group at the C(6) position, a blocked amino
 group at the C(2) position, and blocked hydroxyls at the C(3) and C(4)
 positions;
 .alpha.-D-idose having an unprotected carboxyl at the anomeric C(1)
 position, an unprotected amino group at the C(6) position, and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 .alpha.-D-altrose having an unprotected carboxyl at the anomeric C(1)
 position, an unprotected amino group at the C(6) position, and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 .alpha.-D-gulose having an unprotected carboxyl at the anomeric C(1)
 position, an unprotected amino group at the C(6) position, and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 .alpha.-D-glucose having an unprotected O-glycosidic amino at the anomeric
 C(1) position, an unprotected carboxyl as the C(6) position, and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 D-mannose having an unprotected O-glycosidic amino at the anomeric C(1)
 position, an unprotected carboxyl as the C(6) position, and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 D-galactose having an unprotected O-glycosidic amino at the anomeric C(1)
 position, an unprotected carboxyl as the C(6) position, and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 N-acetyl-D-glucosamine having an unprotected O-glycosidic amino at the
 anomeric C(1) position, an unprotected carboxyl as the C(6) position, a
 blocked amino group at the C(2) position and blocked hydroxyls at the C(3)
 and C(4) positions;
 D-ribose having an unprotected carboxyl at the anomeric C(1) position, an
 unprotected amino group at the C(5) position, and blocked hydroxyls at the
 C(2) and C(3) positions; and
 D-arabinose having an unprotected carboxyl at the anomeric C(1) position,
 an unprotected amino group at the C(5) position, and blocked hydroxyls at
 the C(2) and C(3) positions.
 Preferred carbohydrate amino acid subunits (CA's) include the following:
 D-glucose having a C(1) C.sub.1' -glycosidic carbon bonded to a
 phosphoramidite, an unprotected hydroxyl at the C(6) position and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 D-mannose having a C(1) C.sub.1' -glycosidic carbon bonded to a
 phosphoramidite, an unprotected hydroxyl at the C(6) position and blocked
 hydroxyls at the C(2), C(3), and C(4) positions;
 D-galactose having a C(1) C.sub.1' -glycosidic carbon bonded to a
 phosphoramidite, an unprotected hydroxyl at the C(6) position and blocked
 hydroxyls at the C(2), C(3), and C(4) positions; and
 N-acetyl-D-glucosamine having a C(1) C.sub.1' -glycosidic carbon bonded to
 a phosphoramidite, an unprotected hydroxyl at the C(6) position, a blocked
 amino at the C(2) position, and blocked hydroxyls at the C(3) and C(4)
 positions.
 Scheme 3 outlines a preferred synthesis of suitably protected carbohydrate
 amino acid subunits (CA's) from D-glucose, i.e. compound 46.
 ##STR3##
 Scheme 4 outlines the synthesis of suitably protected carbohydrate amino
 acid subunits (CA's) from N-acetyl-D-glucosamine, i.e. Compound 62.
 ##STR4##
 Scheme 5 summarizes the synthesis of hexamer 74, i.e glucose-glucosamine
 hetero carbopeptoid (CPD).
 ##STR5##
 ##STR6##
 Scheme 6 illustrates the construction of suitably protected and activated
 C-glycoside subunits (CG's) corresponding to glucose.
 ##STR7##
 Scheme 7 illustrates the construction of suitably protected and activated
 C-glycoside subunits (CG's) corresponding to glucosamine.
 ##STR8##
 Scheme 8 summarizes the synthesis of hexamer 116, i.e. glucose-glucosamine
 hetero carbonucleotide (CND).
 ##STR9##
 ##STR10##
 The chemistries illustrated in Schemes 5 and 8 for synthesizing
 heterohexamer CPD 74 and heterohexamer CND 116 can also be employed for
 synthesizing homohexamer CPD's 118 (glucose) and 120 (glucosamine) and
 homohexamer CND's 122 (glucose) and 124 (glucosamine).
 ##STR11##
 In analogy with the construction of oligopeptide and oligonucleotide
 libraries, a oligosaccharide carbopeptoid (CPD) library may be constructed
 by performing using a split synthesis method of oligomerization as
 illustrated in Scheme 500 for carbopeptoids and Scheme 550 for
 carbonucleotoids. For example, the split synthesis may employ beads upon
 which to build the oligomers. Beads are aliquoted into each of a several
 reaction vessels, each reaction vessel containing a different core
 molecule. The core molecules are then allowed to attach to the beads. The
 beads are washed, mixed with one another, and then re-aliquoted (split)
 into a second set of reaction vessels for addition of a second core
 molecule to the first added core molecule. The process is then reiterated
 until the oligomerization process is complete. The resultant library of
 oligosaccharides may then be screened using conventional methods developed
 for oligopeptide and oligonucleotide libraries. Screening an
 oligosaccharide library can lead to the identification of individual
 oligosaccharide components within the library having binding activity
 and/or bioactivity.
 The above oligosaccharide libraries (CPD and CND) may be enlarged by
 introducing additional functionalities into the basic CA's and CG's.
 The above oligosaccharide libraries (CPD and CND) may be further enlarged
 by enlarging the pool of free functional groups on the CA's and CG's and
 employed this enlarged pools of CA's and CG's during the respective split
 synthesis processes.
 Scheme 20 illustrate a protocol published by Fuchs, E. F. et al. (J. Chem
 Ber. 1975, 108, 2254) for the synthesis of CA 45 and 46 from glucose
 pentaacetate. Additionally, Scheme 20 illustrates a synthetic route for CG
 82, also starting from glucose pentaacetate. The reagents and conditions
 for synthesizing CG 82 are provided as follows:
 Steps (a)-(d): according to Fuchs (supra).
 Step (e):
 (1) DMTCl, DMAP, Pyridine; room temperature.
 (2) TESTfl; 0.degree. C.
 Step (f): DIBAL-H, CH.sub.2 Cl.sub.2 ; -78.degree. C.; and
 Step (g): (NCCH.sub.2 CH.sub.2) (NiPr.sub.2)PCl, tetrazole, CH.sub.2
 Cl.sub.2.
 The reagents and conditions for synthesizing CA 46 from CA 45 are provided
 in Step M as follows:
 Step (m): FMOC-Cl, K.sub.2 CO.sub.3, THF, H.sub.2 O; 0.degree. C.
 ##STR12##
 A synthetic route for producing C-glycosides (CG's) with
 .beta.-configuration at the former anomer center is illustrated in Scheme
 21. The starting material (compound 36) is commercially available. The
 reagents and conditions for synthesizing CG 181 and CG 185 are as follows:
 Step (a): Co.sub.2 (CO).sub.8, HSiEt.sub.2 Me, CO.
 Step (b):
 (1) AcOH, H.sub.2 O, THF;
 (2) RuCl.sub.3, NalO.sub.4, CH.sub.3 CN, H.sub.2 O, CCL.sub.4, room
 temperature;
 Step (c): NaOMe, MeOH;
 Step (d):
 (1) DMTCl, DMAP, Pyridine, room temperature;
 (2) TESOTf;
 Step (e): BH.sub.3 -THF;
 Step (f): (NCCH.sub.2 CH.sub.2) (NiPr.sub.2)PCl, tetrazole, Ch.sub.2
 Cl.sub.2 ;
 Step (g):
 (1) 1 equiv TsCl. base;
 (2) TESOTf;
 Step (h): NaN.sub.3 ;
 Step (i): H.sub.2, Pd(OH).sub.2 --C;
 Step (j): FMOC-Cl, base.
 ##STR13##
 ##STR14##
 Synthetic routes for producing with C-glycosides with
 .alpha.-configurations at the former anomeric center, i.e. CG 196 and CG
 1204, are illustrated in Scheme 22. The common starting material for these
 synthetic routes (compound 190) is disclosed by Schmidt, R. R. et al.
 (Liebigs Ann. Chem. 1987, 825). The reagents and conditions for the
 reactions leading to CG 196 and CG 204 are as follows:
 Step (a): reductive debenzylation;
 Step (b):
 (1) equiv TsCl. base;
 (2) TESOTf.
 Step (c): NaN.sub.3.
 Step (d): RuCl.sub.3, NalO.sub.4, CH.sub.3 CN, H.sub.2 O, CCl.sub.4.
 Step (e): H.sub.2, Pd--C.
 Step (f): FMOC-Cl, base.
 Step (g):
 (1) DMTCl, DMAP, Pyridine, room temperature;
 (2) TESOTf.
 Step (h):
 (1) RuCl.sub.3, NalO.sub.4, CH.sub.3 CN, H.sub.2 O, CC14;
 (2) CH.sub.2 N.sub.2.
 Step (i): DIBAL-H.
 Step (j): PPh.sub.3, DIAD, diphenyl phosphoryl azide (DPPA), THF.
 Step (k): KMnO.sub.4, t-BuOH, buffer.
 Reactions for the development of the galactose derived C-glycoside 138 into
 protected CA's and diols is illustrate in Scheme 23. The common starting
 material for these synthetic routes (compound 138) is disclosed by Petrus,
 L. et al. (Chem. zvesti. 1982, 36, 103) The reagents and conditions
 required for the synthesis of compound 209, compound 214, compound 220,
 and compound 224 are indicated below:
 Step (a):
 (1) 1.1 equivalent DMTCl, DMAP, Pyridine, 12 hour, 20.degree. C.;
 (2) TesOTf, CH.sub.2, 0.degree. C., 1 hour, 83%.
 Step (b):
 (1) LAH, ether, reflux, 2 hour;
 (2)FMOC-Cl, K.sub.2 CO.sub.3, THF, H.sub.2 O, 0.degree. C., 1 hour, 55%;
 Step (c): 10% HCOOH in CH.sub.2 Cl.sub.2, 0.degree. C., 2 minutes, 100%.
 Step (d): RuCl.sub.3, NalO.sub.4, CH.sub.3 CN, H.sub.2 O, CCl.sub.4,
 20.degree. C., 10 minutes, 54%.
 Step (e):
 (1) 1 equiv. TsCl, base;
 (2) TESOTf.
 Step (f): NaN.sub.3.
 Step (g): oxidative NEF.
 Step (h): Pd--C, H.sub.2.
 Step (i): FMOC--Cl, base.
 Step (j):
 (1) 1 equiv. PivCl, base;
 (2) TESOTf.
 Step (k):
 (1) oxidative Nef;
 (2) CH.sub.2 N.sub.2.
 Step (1): DIBAL-H.
 Step (m): DMTCl, DMAP, Pyridine.
 Step (n): LAH.
 Step (o): Nef reaction Step (p): LAH.
 ##STR15##
 An exemplary protocol for synthesizing a hexamer carbopeptoid (CPD 234)
 starting from galactose derived CA 214, glucosamine derived CA 62, and
 glucose derived CA, using standard methods for solid phase peptide
 synthesis is illustrated in Scheme 24. The reagents and condition for
 these reactions are as follows:
 Step 1: DCC, HOBT, Et.sub.3, DMF;
 Step 2: Piperidine, DMF
 ##STR16##
 ##STR17##
 SYNTHETIC METHODS
 Preparation of 37
 ##STR18##
 To a solution of .beta.-D-Glucose pentaacetate 36 i n nitromethane from
 Aldrich company (0.13 Molar), is added trimethylsilyl cyanide (3.0
 equivalents) and then SnCl.sub.4 (0.02 equivalents). The mixture is
 stirred for one hour and then an aqueous solution of sodium acetate was
 added to hydrolyze the remaining trimethylsilyl cyanide. The mixture is
 evaporated and the remaining oil is resuspended in dichloromethane and
 washed with sodium acetate solution (1.times.), water (1.times.), brine
 (1.times.) and then dried over magnesium sulphate and concentrated. The
 crude solid is then recrystallized from methanol to yield 37 as a white
 solid (47%). scheme 3 step 1; scheme 9, step a.
 Preparation of 38
 ##STR19##
 The crude product 37 is next dissolved in ethanol (0.15 M) and then
 concentrated H.sub.2 SO.sub.4 (0.01 equivalents-catalytic) is added. The
 reaction mixture is heated to 85.degree. C. for eight hours. The solution
 is next concentrated in vacuo and purification by flash column
 chromatography affords compound 38. scheme 3 step 2.
 Preparation of 39
 ##STR20##
 To a solution of 38 (1.0 equivalents) in pyridine (0.10 Molar), is added
 trimethylacetyl chloride (pivaloyl chloride) (2.5 equivalents) at
 0.degree. C. The reaction is stirred for 2 hours and then diluted with
 diethylether and washed with ammonium chloride (2.times.), copper sulfate
 (2.times.), brine (1.times.), dried over MgSO.sub.4 and concentrated.
 Purification by flash column chromatography affords compound 39. scheme 3
 step 1.
 Preparation of 40
 ##STR21##
 To a solution of 39 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added diisopropylethylamine (3.3 equivalents) at 0.degree. C.
 Subsequent addition of triethylsilyl trifluoromethanesulfonate (3.3
 equivalents) is followed by stirring for 2 hours and then the reaction is
 diluted with diethylether and washed with ammonium chloride (2.times.),
 brine (1.times.) and then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography affords compound 40. scheme 3
 step 2.
 Preparation of 41
 ##STR22##
 To a solution of 40 in ethanol (0.13 Molar), is added sodium ethoxide (0.3
 equivalents) and the reaction mixture is stirred for two hours at room
 temperature. The solution is then concentrated in vacuo and purification
 by flash column chromatography affords compound 41. scheme 3 step 1.
 Preparation of 42
 ##STR23##
 A solution of 41 (1.0 equivalents) in tetrahydrofuran (0.18 M) is treated
 with DPPA (diphenylphosphorylazide, 2.0 equivalents), triphenylphosphine
 (1.3 equivalents) and DIAD (diisopropyl-azo-dicarboxylate, 1.3
 equivalents). The reaction is heated to 80.degree. C. for 3 hours and then
 diluted with ether (2.times.) and washed with 0.5 M aqueous NaOH
 (2.times.). The organic layer is dried over MgSO.sub.4 and evaporated.
 Purification by flash column chromatography affords compound 42. scheme 3
 step 2.
 Preparation of 44
 ##STR24##
 A solution of 42 (1.0 equivalents) is dissolved in ethanol (0.01 M total)
 at 25.degree. C. The mixture is next exposed to 10% Pd/C (0.1 equivalents)
 and is then subsequently capped with a hydrogen balloon at 1 atmosphere.
 The reaction is stirred for 72 hours and is then filtered through celite.
 The crude mixture is subsequently diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 44. scheme 3 step 1.
 Preparation of 45
 ##STR25##
 A solution of 44 (1.0 equivalents) is dissolved in p-dioxanes (0.1 M) and
 then exposed to a solution 3.0 Molar solution of sodium hydroxide (1.5
 equivalents). The reaction is then stirred for 2 hours at 50.degree. C.
 and is subsequently diluted with ether and washed with a solution of
 NH.sub.4 Cl (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 45. scheme 3 step 1.
 Preparation of 46
 To a solution of 45 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added sodium bicarbonate (2.0 equivalents) at 0.degree. C. Subsequent
 addition of 9-fluorenylmethyl chloroformate (FMOC-Cl, 1.2 equivalents) is
 followed by stirring for 2 hours and then the reaction is diluted with
 diethylether and washed with ammonium chloride (2.times.), brine
 (1.times.) and then dried (MgSO.sub.4) and concentrated. Purification by
 flash column chromatography affords compound 46. scheme 3 step 2.
 Preparation of 48
 ##STR26##
 Procedure as described in Methods in Carbohydrate chemistry, Whistler, R.,
 II, 1963, p. 327. A mixture of 80 g anhydrous D-glucosamine hydrochloride
 or D-galactosamine hydrochloride from Aldrich chemical company, in 200 mL.
 Methanol and 20 g Dowex 50 (H+) acidic resin, is stirred at the boiling
 point in a round bottom flask. After 24-hr. reaction time, the resin is
 removed by filtration and ished three times with 20 ml. of methanol. The
 filtrate and ishings are combined and concentrated to about 125 ml by
 rotovap. The concentrate is allowed to cool to room temperature and the
 product crystallizes overnight.
 To a solution of free amine, in chloroform (0.5 M), is added phthalic
 anhydride (1.5 equiv.) and the reaction mixture is allowed to reflux at
 70.degree. C. for 4 h. The product is then crystallized and carried onto
 the next step.
 To a solution of triol in methylene chloride (0.5 M), is added acetic
 anhydride (3.5 equiv.) and triethyl amine (3.5 equiv.) and the reaction
 mixture is allowed to stir at 0.degree. C. for 4 h. The product 48, is
 then crystallized or purified by flash column chromatography and carried
 onto the next step.
 Preparation of 50
 ##STR27##
 To a solution of N-phthalamido-D-Glucosamine tetraacetae 48 in nitromethane
 (0.13 Molar), is added trimethylsilyl cyanide (3.0 equivalents) and then
 SnCl.sub.4 (0.02 equivalents). The mixture is stirred for one hour and
 then an aqueous solution of sodium acetate was added to hydrolyze the
 remaining trimethylsilyl cyanide. The mixture is evaporated and the
 remaining oil is resuspended in dichloromethane and washed with sodium
 acetate solution (1.times.), water (1.times.), brine (1.times.) and then
 dried over magnesium sulphate and concentrated. The crude solid is then
 recrystallized from methanol to yield 50 as a white solid (47%). scheme 4.
 Preparation of 52
 The crude product 50 is next dissolved in ethanol (0.15 M) and then
 concentrated H.sub.2 SO.sub.4 (0.01 equivalents-catalytic) is added. The
 reaction mixture is heated to 85.degree. C. for eight hours. The solution
 is next concentrated in vacuo and purification by flash column
 chromatography affords compound 52. scheme 4.
 Preparation of 54
 ##STR28##
 A solution of 52 (1.0 equivalents) is dissolved in methanol (0.1 M total).
 The reaction is then charged with acetic anhydride (1.1 equivalents) and
 is subsequently stirred for 2 hours at 30.degree. C. The reaction is next
 diluted with ether and washed with NaHCO.sub.3 (3.times.), brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography affords compound 54. scheme 4.
 Preparation of 55
 ##STR29##
 To a solution of 54 (1.0 equivalents) in pyridine (0.10 Molar), is added
 trimethylacetylchloride (pivaloyl chloride) (2.5 equivalents) at 0.degree.
 C. The reaction is stirred for 2 hours and then diluted with diethylether
 and washed with ammonium chloride (2.times.), copper sulfate (2.times.),
 brine (1.times.), dried over MgSO.sub.4 and concentrated. Purification by
 flash column chromatography affords compound 55. scheme 4.
 Preparation of 56
 ##STR30##
 To a solution of 55 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added diisopropylethylamine (2.2 equivalents) at 0.degree. C.
 Subsequent addition of triethylsilyl trifluoromethanesulfonate (2.2
 equivalents) is followed by stirring for 2 hours and then the reaction is
 diluted with diethylether and washed with ammonium chloride (2.times.),
 brine (1.times.) and then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography affords compound 56. scheme 4.
 Preparation of 57
 ##STR31##
 To a solution of 56 in ethanol (0.13 Molar), is added sodium ethoxide (0.3
 equivalents) and the reaction mixture is stirred for two hours at room
 temperature. The solution is then concentrated in vacuo and purification
 by flash column chromatography affords compound 57. scheme 4.
 Preparation of 58
 ##STR32##
 A solution of 57 (1.0 equivalents) in tetrahydrofuran (0.18 M) is treated
 with DPPA (diphenylphosphorylazide, 2.0 equivalents), triphenylphosphine
 (1.3 equivalents) and DIAD (diisopropyl-azo-dicarboxylate, 1.3
 equivalents). The reaction is heated to 80.degree. C. for 3 hours and then
 diluted with ether (2.times.) and washed with 0.5 M aqueous NaOH
 (2.times.). The organic layer is dried over MgSO.sub.4 and evaporated.
 Purification by flash column chromatography affords compound 58. scheme 4.
 Preparation of 60
 ##STR33##
 A solution of 58 (1.0 equivalents) is dissolved in ethanol (0.01 M total)
 at 25.degree. C. The mixture is next exposed to 10% Pd/C (0.1 equivalents)
 and is then subsequently capped with a hydrogen balloon at 1 atm. The
 reaction is stirred for 72 hours and is then filtered through celite. The
 crude mixture is subsequently diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 60. scheme 4.
 Preparation of 61
 ##STR34##
 A solution of 60 (1.0 equivalents) is dissolved in p-dioxanes (0.1 M) and
 then exposed to a solution 3.0 Molar solution of sodium hydroxide (1.5
 equivalents). The reaction is then stirred for 2 hours at 50.degree. C.
 and is subsequently diluted with ether and washed with a solution of
 NH.sub.4 Cl (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 61. scheme 4.
 Preparation of 62
 ##STR35##
 To a solution of 61 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added sodium bicarbonate (2.0 equivalents) at 0.degree. C. Subsequent
 addition of 9-fluorenylmethyl chloroformate (FMOC-C.sub.1' 1.2
 equivalents) is followed by stirring for 2 hours and then the reaction is
 diluted with diethylether and washed with ammonium chloride (2.times.),
 brine (1.times.) and then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography affords compound 62. scheme 4.
 Preparation of 63
 ##STR36##
 To a stirred solution of the acid 46 (1.0 equivalents) and the amine 60
 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25.degree. C., is
 added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Next
 dicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction is
 stirred for 14 hours. The mixture is diluted with ether, filtered and the
 filtrate is washed with aqueous NaHCO.sub.3 (2.times.), water (2.times.),
 and brine (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated. Purification by flash column chromatography affords compound
 63. scheme 5 step 1.
 Preparation of 64
 ##STR37##
 To a stirred solution of 63 (1.0 equivalents) in dimethylformamide (0.10
 Molar) at 25.degree. C., is added piperidine (1.1 equivalents). The
 reaction is stirred for 1 hour and is then diluted with ether, and washed
 with aqueous CuSO.sub.4 (2.times.), water (2.times.), and brine
 (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated. Purification by flash column chromatography affords compound
 64. scheme 5 step 2.
 Preparation of 65
 ##STR38##
 To a stirred solution of the acid 62 (1.0 equivalents) and the amine 64
 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25.degree. C., is
 added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerous
 iterations can be performed using the acid 62 or intermixing with other
 acids including for example acid 46 to form successive oligomers where n=2
 to infinity (a hexamer is shown in scheme 5) to obtain large carbopeptoid
 libraries. Next dicyclohexylcarbodiimide (1.2 equivalents) is added and
 the reaction is stirred for 14 hours. The mixture is diluted with ether,
 filtered and the filtrate is washed with aqueous NaHCO.sub.3 (2.times.),
 water (2.times.), and brine (2.times.). The organic phase is dried over
 MgSO.sub.4 and then concentrated. Purification by flash column
 chromatography affords compound 65. scheme 5 step 1.
 Preparation of 66
 ##STR39##
 To a stirred solution of 65 (1.0 equivalents) in dimethylformamide (0.10
 Molar) at 25.degree. C., is added piperidine (1.1 equivalents). The
 reaction is stirred for 1 hour and is then diluted with ether, and washed
 with aqueous CuSO.sub.4 (2.times.), water (2.times.), and brine
 (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated. Purification by flash column chromatography affords compound
 66. Note: numerous iterations can be performed using variable length
 oligomers of 66 to form peptoid oligomers where n=2 to infinity (a hexamer
 is shown in scheme 5). scheme 5 step 2.
 Preparation of 67
 ##STR40##
 To a stirred solution of the acid 46 (1.0 equivalents) and the amine 66
 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25.degree. C., is
 added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerous
 iterations can be performed using the acid 46 or intermixing with other
 acids including for example acid 62, to form successive oligomers where
 n=2 to infinity (a hexamer is shown in scheme 5) to obtain large
 carbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents) is
 added and the reaction is stirred for 14 hours. The mixture is diluted
 with ether, filtered and the filtrate is washed with aqueous NaHCO.sub.3
 (2.times.), water (2.times.), and brine (2.times.). The organic phase is
 dried over MgSO.sub.4 and then concentrated. Purification by flash column
 chromatography affords compound 67. scheme 5 step 1.
 Preparation of 68
 ##STR41##
 To a stirred solution of 67 (1.0 equivalents) in dimethylformamide (0.10
 Molar) at 25.degree. C., is added piperidine (1.1 equivalents). The
 reaction is stirred for 1 hour and is then diluted with ether, and washed
 with aqueous CuSO.sub.4 (2.times.), water (2.times.), and brine
 (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated. Purification by flash column chromatography affords compound
 68. Note: numerous iterations can be performed using variable length
 oligomers of 68 to form peptoid oligomers where n=2 to infinity (a hexamer
 is shown in scheme 5). scheme 5 step 2.
 Preparation of 69
 ##STR42##
 To a stirred solution of the acid 62 (1.0 equivalents) and the amine 68
 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25.degree. C., is
 added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerous
 iterations can be performed using the acid 62, or intermixing with other
 acids including for example acid 46, to form successive oligomers where
 n=2 to infinity (a hexamer is shown in scheme 5) to obtain large
 carbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents) is
 added and the reaction is stirred for 14 hours. The mixture is diluted
 with ether, filtered and the filtrate is washed with aqueous NaHCO.sub.3
 (2.times.), water (2.times.), and brine (2.times.). The organic phase is
 dried over MgSO.sub.4 and then concentrated. Purification by flash column
 chromatography affords compound 69. scheme 5 step 1.
 Preparation of 70
 ##STR43##
 To a stirred solution of 69 (1.0 equivalents) in dimethylformamide (0.10
 Molar) at 25.degree. C., is added piperidine (1.1 equivalents). The
 reaction is stirred for 1 hour and is then diluted with ether, and washed
 with aqueous CuSO.sub.4 (2.times.), water (2.times.), and brine
 (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated. Purification by flash column chromatography affords compound
 70. Note: numerous iterations can be performed using variable length
 oligomers of 70 to form peptoid oligomers where n=2 to infinity (a hexamer
 is shown in scheme 5). scheme 5 step 2.
 Preparation of 71
 ##STR44##
 To a stirred solution of the acid 46 (1.0 equivalents) and the amine 70
 (1.1 equivalents) in dimethylformamide (0.10 Molar) at 25.degree. C., is
 added 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Note: numerous
 iterations can be performed using the acid 46 or intermixing with other
 acids including for example acid 62, to form successive oligomers where
 n=2 to infinity (a hexamer is shown in scheme 5) to obtain large
 carbopeptoid libraries. Next dicyclohexylcarbodiimide (1.2 equivalents) is
 added and the reaction is stirred for 14 hours. The mixture is diluted
 with ether, filtered and the filtrate is washed with aqueous NaHCO.sub.3
 (2.times.), water (2.times.), and brine (2.times.). The organic phase is
 dried over MgSO.sub.4 and then concentrated. Purification by flash column
 chromatography affords compound 71. scheme 5 step 1.
 Preparation of 72
 ##STR45##
 To a stirred solution of 71 (1.0 equivalents) in dimethylformamide (0.10
 Molar) at 25.degree. C., is added piperidine (1.1 equivalents). The
 reaction is stirred for 1 hour and is then diluted with ether, and washed
 with aqueous CuSO.sub.4 (2.times.), water (2.times.), and brine
 (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated. Purification by flash column chromatography affords compound
 72. Note: numerous iterations can be performed using variable length
 oligomers of 72 to form peptoid oligomers where n=2 to infinity (a hexamer
 is shown in scheme 5). scheme 5 step 2.
 Preparation of 74
 ##STR46##
 To a stirred solution of 72 (1.0 equivalents) in acetonitrile (0.50 Molar)
 is added an HF-pyridine solution (0.50 M) from Aldrich chemical company.
 The reaction is allowed to stir for five hours and is then condensed. The
 crude 73 oligomer is then resuspended in p-dioxane (0.50 Molar) to which
 is added a 3.0 Molar solution of NaOH (3.0 equivalents). The reaction is
 stirred for 1 hour at 50.degree. C. and is then quenched with aqueous
 NH.sub.4 Cl (2.times.) and subsequently lyophilized. Purification by HPLC
 chromatography affords compound 74. scheme 5.
 Preparation of 76
 ##STR47##
 To a solution of .beta.-D-Glucose pentaacetate 36 in nitromethane from
 Aldrich company (0.13 Molar), is added trimethylsilylcyanide (3.0
 equivalents) and then tin tetrachloride (0.02 equivalents). Note: other
 pyranose sugars such as .beta.-D-Mannose, .beta.-D-Galactose pentaacetate
 and other lewis acids such as BF.sub.3 OEt.sub.2 may be used for
 alternative derivatives. The mixture is stirred for one hour and then an
 aqueous solution of sodium acetate was added to hydrolyze the remaining
 trimethylsilylcyanide. The mixture is evaporated and the remaining oil is
 resuspended in dichloromethane and washed with sodium acetate solution
 (1.times.), water (1.times.), brine (1.times.) and then dried over
 magnesium sulphate and concentrated. The crude product is next dissolved
 in ethanol (or methanol if the O-methyl glycoside is desired as in scheme
 20), (0.15 M) and then concentrated H.sub.2 SO.sub.4 (0.01 equivalents) is
 added. The reaction mixture is heated to 85.degree. C. for eight hours.
 The solution is next concentrated in vacuo and purification by flash
 column chromatography affords compound 76. scheme 6; 76, scheme 20 (as the
 O-methyl glycoside).
 Preparation of 78
 ##STR48##
 To Tetrol 76 (1.0 equivalents) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (4.4 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (4.4 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 78, scheme 6; 78, scheme 20 (as the O-methyl glycoside).
 Preparation of 80
 ##STR49##
 To a solution of 78 (1.0 equivalents) in methylene chloride (0.10 Molar) is
 added a 1.0 M solution of DIBALH in methylene chloride from Aldrich
 chemical company (1.2 equivalents) at 0.degree. C. Subsequent stirring for
 2 hours is followed by dilution with diethylether and washing with
 sodium-potassium tartrate (2.times.), brine (1.times.) and then
 MgSO.sub.4. The solution is then concentrated and purification by flash
 column chromatography affords compound 80. scheme 6.
 Preparation of 82
 ##STR50##
 To a solution of 80 (1.0 equivalents) in methylene chloride (0.10 M), is
 added diisopropylethylamine (4.0 equivalents) at 25 .degree. C. The
 reaction is stirred for 5 minutes and then
 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equivalents) is
 added, as prepared from the procedures of Sinha et al. Nucl. Acids Res.
 1984, 12, 4539. After 15 minutes the reaction is complete and is next
 diluted with ether and next washed with brine (1.times.) and is then dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 30% ethyl acetate in petroleum ether) affords compound 82 (66%
 yield). scheme 6.
 Preparation of 84
 ##STR51##
 To 80 (1.0 equivalents) in methylene chloride (0.10 Molar) at 0.degree. C.,
 is added diisopropylethylamine (1.1 equivalents). Subsequent addition of
 triethylsilyl trifluoromethanesulfonate (1.1 equivalents) is followed by
 stirring for 2 hours and then the reaction is diluted with diethylether
 and washed with ammonium chloride (2.times.), brine (1.times.) and then
 dried (MgSO.sub.4) and concentrated. The crude is then resuspended in
 nitromethane and exposed to 10% Cl.sub.3 COOH (1.1 equivalents) in THF
 (0.10 Molar). The reaction is stirred at 0.degree. C. for 2 hours and is
 then diluted with ether and washed with sodium bicarbonate (2.times.),
 brine (1.times.) and then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography affords compound 84. scheme 6.
 Preparation of 86
 ##STR52##
 To a solution of N-phthalamido-D-Glucosamine tetraacetate 48 in
 nitromethane (0.13 Molar), is added trimethylsilyl cyanide (3.0
 equivalents) and then SnCl.sub.4 (0.02 equivalents). The mixture is
 stirred for one hour and then an aqueous solution of sodium acetate was
 added to hydrolyze the remaining trimethylsilyl cyanide. The mixture is
 evaporated and the remaining oil is resuspended in dichloromethane and
 washed with sodium acetate solution (1.times.), water (1.times.), brine
 (1.times.) and then dried over magnesium sulphate and concentrated. The
 crude product is next dissolved in ethanol (0.15 M) and then concentrated
 H.sub.2 SO.sub.4 (0.04 equivalents) is added. The reaction mixture is
 heated to 85.degree. C. for eight hours. The solution is next concentrated
 in vacuo and is then resuspended in methanol (0.10 M) and acetic anhydride
 (1.1 equivalents) from Aldrich company is added in one step. After 2
 hours, condensation and purification by flash column chromatography
 affords compound 86. scheme 7.
 Preparation of 88
 ##STR53##
 To Triol 86 (1.0 equivalents) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 88. scheme 7.
 Preparation of 90
 ##STR54##
 To a solution of 88 (1.0 equivalents) in methylene chloride (0.10 Molar) is
 added a 1.0 M solution of DIBALH in methylene chloride from Aldrich
 chemical company (1.2 equivalents) at 0.degree. C. Subsequent stirring for
 2 hours is followed by dilution with diethylether and washing with
 sodium-potassium tartrate (2.times.), brine (1.times.) and then
 MgSO.sub.4. The solution is then concentrated and purification by flash
 column chromatography affords compound 90. scheme 7.
 Preparation of 92
 ##STR55##
 To a solution of 90 (1.0 equivalents) in methylene chloride (0.10 M), is
 added diisopropylethylamine (4.0 equivalents) at 25.degree. C. The
 reaction is stirred for 5 minutes and then
 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equivalents) is
 added, as prepared from the procedures of Sinha et al. Nucl. Acids Res.
 1984, 12, 4539. After 15 minutes the reaction is complete and is next
 diluted with ether and next washed with brine (1.times.) and is then dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 30% ethyl acetate in petroleum ether) affords compound 92 (66%
 yield). scheme 7.
 Preparation of 94
 ##STR56##
 To 90 (1.0 equivalents) in methylene chloride (0.10 Molar) at 0.degree. C.,
 is added diisopropylethylamine (1.1 equivalents). Subsequent addition of
 triethylsilyl trifluoromethanesulfonate (1.1 equivalents) is followed by
 stirring for 2 hours and then the reaction is diluted with diethylether
 and washed with ammonium chloride (2.times.), brine (1.times.) and then
 dried (MgSO.sub.4) and concentrated. The crude is then resuspended in
 nitromethane and exposed to 10% Cl.sub.3 COOH (1.1 equivalents) in THF
 (0.10 Molar). The reaction is stirred at 0.degree. C. for 2 hours and is
 then diluted with ether and washed with sodium bicarbonate (2.times.),
 brine (1.times.) and then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography affords compound 94. scheme 7.
 Preparation of 98 (Homodimer Scheme 8)
 To a solution of 94 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 82 (3.0 equivalents) in methylene chloride (1.0 M),
 is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and I.sub.2 (4.0 equivalents), 2,6
 lutidine (4.0 equivalents) in THF (1.0 M) is added to oxidize the
 phosphoamidate to the phosphate (Alternatively m-chloroperoxybenzoic acid
 (4.5 equivalents) is added). The reaction is next stirred for an
 additional 5 minutes and is next diluted with ether and washed with brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography and then the product is suspended in acetic
 acid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at
 25.degree. C. The reaction is then diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 98 (scheme 8).
 Preparation of 102 (Heterotrimer Scheme 8)
 To a solution of 98 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 92 (3.0 equivalents) in methylene chloride (1.0 M),
 is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and I.sub.2 (4.0 equivalents), 2,6
 lutidine (4.0 equivalents) in THF (1.0 M) is added to oxidize the
 phosphoamidate to the phosphate (Alternatively m-chloroperoxybenzoic acid
 (4.5 equivalents) is added). The reaction is next stirred for an
 additional 5 minutes and is next diluted with ether and washed with brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography and then the product is suspended in acetic
 acid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at
 25.degree. C. The reaction is then diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 102 (scheme 8).
 Preparation of 106 (Heterotetramer Scheme 8)
 To a solution of 102 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 82 (3.0 equivalents) in methylene chloride (1.0 M),
 is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and I.sub.2 (4.0 equivalents), 2,6
 lutidine (4.0 equivalents) in THF (1.0 M) is added to oxidize the
 phosphoamidate to the phosphate (Alternatively m-chloroperoxybenzoic acid
 (4.5 equivalents) is added). The reaction is next stirred for an
 additional 5 minutes and is next diluted with ether and washed with brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography and then the product is suspended in acetic
 acid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at
 25.degree. C. The reaction is then diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 106 (scheme 8).
 Preparation of 110 (Heteropentamer Scheme 8)
 To a solution of 106 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 92 (3.0 equivalents) in methylene chloride (1.0 M),
 is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and I.sub.2 (4.0 equivalents), 2,6
 lutidine (4.0 equivalents) in THF (1.0 M) is added to oxidize the
 phosphoamidate to the phosphate (Alternatively m-chloroperoxybenzoic acid
 (4.5 equivalents) is added). The reaction is next stirred for an
 additional 5 minutes and is next diluted with ether and washed with brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography and then the product is suspended in acetic
 acid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at
 25.degree. C. The reaction is then diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 110 (scheme 8).
 Preparation of 114 (heterohexamer scheme 8)
 To a solution of 110 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 82 (3.0 equivalents) in methylene chloride (1.0 M),
 is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and I.sub.2 (4.0 equivalents), 2,6
 lutidine (4.0 equivalents) in THF (1.0 M) is added to oxidize the
 phosphoamidate to the phosphate (Alternatively m-chloroperoxybenzoic acid
 (4.5 equivalents) is added). The reaction is next stirred for an
 additional 5 minutes and is next diluted with ether and washed with brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography and then the product is suspended in acetic
 acid-tetrahydrofuran-water (3:1:1), (0.01 M) and stirred for 18 hours at
 25.degree. C. The reaction is then diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 114 (scheme 8).
 Preparation of 116 (heterohexamer scheme 8)
 To a solution of 114 (1.0 equivalents) in methylene chloride (0.10 M), is
 added a solution of HF-pyridine (1.0 M) at 0.degree. C. The reaction is
 next stirred for an additional 30 minutes and is next diluted with ether
 and washed with a saturated solution of sodium bicarbonate (3.times.),
 copper sulfate solution to remove the pyridine (2.times.) brine
 (1.times.), dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography and then the product is resuspended in concentrated
 aqueous ammonium hydroxide and acetonitrile (1:1), (0.1 M total). The
 reaction is then stirred for 2 hours at 50.degree. C. and is subsequently
 diluted with ether and washed with NaHCO.sub.3 (3.times.), brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography affords compound 116 scheme 8.
 ##STR57##
 ##STR58##
 Preparation of 125
 ##STR59##
 To a solution of .beta.-D-Glucose pentaacetate in nitromethane from Aldrich
 company (0.13 Molar), is added trimethylsilylcyanide (3.0 equivalents) and
 then borontrifluoride etherate (0.02 equivalents). Note: other pyranose
 sugars such as .beta.-D-Mannose, .beta.-D-Galactose pentaacetate and other
 lewis acids such as SnCl.sub.4, may be used for alternative derivatives.
 The mixture is stirred for one hour and then an aqueous solution of sodium
 acetate was added to hydrolyze the remaining trimethylsilylcyanide. The
 mixture is evaporated and the remaining oil is resuspended in
 dichloromethane and washed with sodium acetate solution (1.times.), water
 (1.times.), brine (1.times.) and then dried over magnesium sulphate and
 concentrated. The crude solid is then recrystallized from methanol to
 yield 125 (also 37) as a white solid (47%). scheme 9 step a.
 Preparation of 126
 ##STR60##
 To a solution of 125 in methanol (0.13 Molar), is added sodium methoxide
 (0.3 equivalents) and the reaction mixture is stirred for two hours at
 room temperature. The dark brown solution is then concentrated in vacuo to
 give a dark brown syrup of compound 126 which is carried on without
 purification as a crude oil for the next step. scheme 9 step b.
 Preparation of 127
 ##STR61##
 The crude product 126 is dissolved in 25% NaOH (0.5 M) and heated at reflux
 for 18 hours (vigorous reflux is necessary). Next, the solution is diluted
 with an addition of water (0.1 M) and to this solution is added Amberlite
 112120 resin (H.sup.+ -form) and is then stirred. The supernatant is then
 decanted and the resin is washed until the eluate is colorless. The eluate
 is then collected, condensed and azeotroped with MeOH which yields 127 as
 a crude, pale yellow syrup (47%).
 Preparation of 130
 ##STR62##
 The crude product 127 is next dissolved in methanol (0.15 M) and then
 concentrated HCl (0.01 equivalents) is added. The reaction mixture is
 heated to 85.degree. C. for eight hours. The solution is next concentrated
 in vacuo and purification by flash column chromatography (silica, 20%
 methanol in ethyl acetate), affords compound 130 as a white solid (60%
 yield). scheme 9 step d.
 Preparation of 131
 ##STR63##
 To a solution of 130 (1.0 equivalents) in dimethylformamide (0.23 Molar),
 is added imidazole (2.5 equivalents) at 0.degree. C. Subsequent addition
 of tert-Butyl-dimethylsilylchloride (2.5 equivalents) is followed by
 stirring for 2 hours and then the reaction is diluted with diethylether
 and washed with ammonium chloride (2.times.), brine (1.times.) and then
 dried (MgSO.sub.4) and concentrated. Purification by flash column
 chromatography (silica, 50% ethyl acetate) affords compound 131 as a white
 solid (93% yield). scheme 9 step e Note: the molecule can be protected
 with other primary directing protecting groups such as DMT
 (dimethoxytrityl), and TBDPS tert-butyldiphenlysilyl, etc.
 Preparation of 132
 ##STR64##
 To a solution of 1 3 1 (1.0 equivalents) in dimethylformamide (0.23 M), is
 added Ag.sub.2 O (6.0 equivalents) at 25.degree. C. Benzyl bromide (9.0
 equivalents) is next added and the reaction is allowed to stir for 20
 hours. The reaction is diluted with diethylether and washed with ammonium
 chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography (silica, 20%
 ethyl acetate) affords compound 132 (83% yield). scheme 9 step f Note: the
 choice of the protecting group is relative and the molecule can be
 protected with other protecting groups at C2, C3, C4, such as PMB
 (paramethoxybenzyl), TES (triethylsilyl), TBS (tertbutyldimethylsilyl),
 etc.
 Preparation of 134
 ##STR65##
 To a solution of 132 (1.0 equivalents) in tetrahydrofuran (0.08 M), is
 added diisobutylaluminumhydride (DIBALH) (3.0 equivalents) at 0.degree. C.
 The reaction is stirred for 1 hour and then quenched with methanol and
 diluted with ether. The reaction is next worked-up with ammonium chloride
 (2.times.), brine (1.times.) and is then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography (silica, 20%
 ethyl acetate) affords compound 134 (66% yield). scheme 9 step g.
 Preparation of 136
 ##STR66##
 To a solution of 134 (1.0 equivalents) in pyridine (10.0 equivalents), is
 added naphthoyl chloride (3.0 equivalents) from Aldrich company (3.0
 equivalents) at 25.degree. C. The reaction is stirred for 45 minutes and
 then diluted with ether and worked-up with a saturated solution of
 CuSO.sub.4 (2.times.), brine (1.times.) and is then dried (MgSO.sub.4) and
 concentrated. The crude product is then exposed to acetic
 acid/tetrahydrofuran/water (3:1:1) at 25.degree. C. and allowed to stir
 for 15 hours. The reaction is then diluted with ether and worked-up with
 brine (2.times.) and is then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography (silica, 20% ethyl acetate)
 affords compound 136 (95% yield). Note: alternatively, one could
 originally protect the C7 position as a DMT (dimethoxytrityl)
 functionality and protect the C1 position as a TES (triethyl silyl) group.
 Subsequent mild acid hydrolysis of the DMT group leads to the above
 compound with the TES group at the C1 position and a free hydroxyl at the
 C7 position. scheme 9 step h.
 Preparation of 138
 ##STR67##
 To a solution of 134 (1.0 equivalents) in methylene chloride (0.10 M), is
 added diisopropylethylamine (4.0 equivalents) at 25.degree. C. The
 reaction is stirred for 5 minutes and then
 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equivalents) is
 added, as prepared from the procedures of Sinha et al. Nucl. Acids Res.
 1984, 12, 4539. After 15 minutes the reaction is complete and is next
 diluted with ether and next washed with brine (1.times.) and is then dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 30% ethyl acetate in petroleum ether) affords compound 138 (66%
 yield). scheme 9 step i. It should be noted that the oligomerization
 process as shown below in scheme 9, uses the same C-glycoside 138 in an
 iterative fashion. The process can be extended however to include a pool
 of random or ordered C-glycosides as depicted in scheme 8.
 Preparation of 140
 ##STR68##
 To a solution of 136 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 138 (3.0 equivalents) in methylene chloride (1.0
 M), is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and m-chloroperoxybenzoic acid (4.5
 equivalents) is added. The reaction is stirred for an additional 5 minutes
 and is next diluted with ether and washed with brine (1.times.) and dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 50% ethyl acetate in petroleum ether) affords compound 140 (97%
 yield). scheme 9 step j. Note the process can iterate as many times as
 possible to build large carbonucleotide libraries.
 Preparation of 142
 ##STR69##
 A solution of 140 (1.0 equivalents) in acetic acid-tetrahydrofuran-water
 (3:1:1), (0.01 M) is stirred for 18 hours at 25.degree. C. The reaction is
 then diluted with ether and washed with NaHCO.sub.3 (3.times.), brine
 (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by flash
 column chromatography (silica, 60% ethyl acetate in petroleum ether)
 affords compound 142 (95% yield). scheme 9 step k. Note the process can
 iterate as many times as possible to build large carbonucleotide
 libraries.
 Preparation of 144
 ##STR70##
 To a solution of 138 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 142 (3.0 equivalents) in methylene chloride (1.0
 M), is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and m-chloroperoxybenzoic acid (4.5
 equivalents) is added. The reaction is stirred for an additional 5 minutes
 and is next diluted with ether and washed with brine (1.times.) and dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 50% ethyl acetate in petroleum ether) affords compound 144 (97%
 yield). scheme 9 step j. Note the process can iterate as many times as
 possible to build large carbonucleotide libraries.
 Preparation of 146
 ##STR71##
 A solution of 144 (1.0 equivalents) in acetic acid-tetrahydrofuran-water
 (3:1:1), (0.01 M total) is stirred for 18 hours at 25.degree. C. The
 reaction is then diluted with ether and washed with NaHCO.sub.3
 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography (silica, 60% ethyl acetate in
 petroleum ether) affords compound 146 (95% yield). scheme 9 step k. Note
 the process can iterate as many times as possible to build large
 carbonucleotide libraries.
 Preparation of 148
 ##STR72##
 To a solution of 138 (1.0 equivalents) in methylene chloride (0.10 M), is
 added 1-H-tetrazole from Aldrich company (10.0 equivalents) at 25.degree.
 C. Next, a solution of 146 (3.0 equivalents) in methylene chloride (1.0
 M), is added dropwise with stirring at 25.degree. C. After 25 minutes, the
 mixture is cooled to 0.degree. C. and m-chloroperoxybenzoic acid (4.5
 equivalents) is added. The reaction is stirred for an additional 5 minutes
 and is next diluted with ether and washed with brine (1.times.) and dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 50% ethyl acetate in petroleum ether) affords compound 148 (97%
 yield). scheme 9 step j. Note the process can iterate as many times as
 possible to build large carbonucleotide libraries.
 Preparation of 150
 ##STR73##
 A solution of 148 (1.0 equivalents) in acetic acid-tetrahydrofuran-water
 (3:1:1), (0.01 M total) is stirred for 18 hours at 25.degree. C. The
 reaction is then diluted with ether and washed with NaHCO.sub.3
 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography (silica, 60% ethyl acetate in
 petroleum ether) affords compound 150 (95% yield). scheme 9 step k. Note
 the process can iterate as many times as possible to build large
 carbonucleotide libraries.
 Preparation of 152
 ##STR74##
 A solution of 150 (1.0 equivalents) is dissolved in concentrated aqueous
 ammonium hydroxide and acetonitrile (1:1), (0.1 M total). The reaction is
 then stirred for 2 hours at 50.degree. C. and is subsequently diluted with
 ether and washed with NaHCO.sub.3 (3.times.), brine (1.times.) and dried
 (MgSO.sub.4) and concentrated. Purification by flash column chromatography
 (silica, 80% ethyl acetate in petroleum ether) affords compound 152 (88%
 yield). scheme 9 step L.
 Preparation of 154
 ##STR75##
 A solution of 152 (1.0 equivalents) is dissolved in a mixture of
 ethanol-tetrahydrofuran-acetic acid (2:1:1), (0.01 M total) at 25.degree.
 C. The mixture is next exposed to 10% Pd/C (1.0 equivalents) and is then
 subsequently capped with a hydrogen balloon at 1 atmosphere. The reaction
 is stirred for 72 hours and is then filtered through celite. The crude
 mixture is subsequently diluted with ether and washed with NaHCO.sub.3
 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography (silica, 100% ethyl acetate in
 petroleum ether) affords compound 154 (78% yield). scheme 9 step m.
 Preparation of 174 (R Group=OTES, NPhth or NHAc)
 To a solution of tetraacetate derived from 36 or 48 (glucose or glucosamine
 derived) in methylene chloride (0.1 molar) is added a 1.0 molar solution
 of Co.sub.2 (CO).sub.8 (1.5 equivalents ) in methylene chloride and
 diethylmethylsilane (1.5 equivalents) at 0.degree. C. To the stirring
 reaction mixture, a stream of carbon monoxide is bubbled at 1 ml per 10
 seconds for 30 minutes. The reaction mixture is then quenched with water
 (1.5 equivalents), diluted with ether, washed with sodium bicarbonate
 (2.times.), brine (1.times.) and dried over magnesium sulfate. The crude
 is purified by column chromatography and affords product 174.
 Preparation of 176 (R Group=OTES, NPhth or NHAc)
 To a solution of compound 174 in acetonitrile/water (1:1 ratio, 0.1 molar
 combined), is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4 (4.0 equiv.)
 at 25.degree. C. and the muddy black mixture is allowed to stir for 1.5 h.
 The mixture is then diluted with ether (25 mL), washed with water
 (2.times.5.0 mL) and brine (1.times.5 mL). The aqueous layer is back
 extracted (2.times.), recombined, and the organic layer was then dried
 MgSO.sub.4 and evaporated. Purification by flash column chromatography
 yields the desired product 176.
 Preparation of 178 (R Group=OTES, NPhth or NHAc)
 A solution of triacetate 176 (1.0 equiv.) in methanol (0.5 M), is treated
 with NaOMe (0.4 equiv.) and allowed to stir at 25.degree. C. for 24 h. The
 reaction mixture is then condensed and purified by flash column
 chromatography to afford compound 178.
 Preparation of 180 (R Group=OTES, NPhth or NHAc)
 To triol 178 (1.0 equivalents) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (1.5 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords the
 intermediate acid, which is then resuspended in THF (1.0 M) and exposed to
 a 1.0 M solution of BH.sub.3 -THF (1.5 equivalents) at 0.degree. C. for 1
 hour. The reaction is then quenched with methanol for an additional hour
 and the crude is then diluted with diethylether and washed with ammonium
 chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords the
 desired tetraprotected alcohol 180.
 Preparation of 181 (R Group=OTES, NPhth or NHAc)
 To a solution of 180 (1.0 equivalents) in methylene chloride (0.10 M), is
 added tetrazole (4.0 equivalents) at 25.degree. C. The reaction is stirred
 for 5 minutes and then 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite
 (1.5 equiv.) is added, as prepared from the procedures of Sinha et al.
 Nucl. Acids Res. 1984, 12, 4539. After 15 minutes the reaction is complete
 and is next diluted with ether and next washed with brine (1.times.) and
 is then dried (MgSO.sub.4) and concentrated. Purification by flash column
 chromatography (silica, 30% ethyl acetate in petroleum ether) affords
 compound 181 (66% yield). scheme 21.
 Preparation of 182 (R Group=OTES, NPhth or NHAc)
 To a solution of triol 178 (0.0 equiv.) in CH.sub.2 Cl.sub.2 (0.5 M) at
 0.degree. C., was added triethylamine (1.2 equiv.), 4-DMAP (0.10 equiv.)
 and then TOSCI (1.1 equiv.). The reaction is stirred for 1 h and then is
 quenched with saturated ammonium chloride (1.5 mL), diluted with ethyl
 acetate (25 mL), washed with water (2.times.5 mL), brine (1.times.5 mL),
 back-extracted (2.times.), recombined, dried (MgSO.sub.4) and evaporated.
 The compound is purified by flash column chromatography and then a
 solution of the crude intermediate (1.0 equivalents) is dissolved in
 methylene chloride (0.10 Molar) and diisopropylethylamine (2.2
 equivalents) is added at 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (2.2 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords the
 protected tosylate/acid 182.
 Preparation of 183 (R group=OTES. NPhth or NHAc)
 To a solution of triol 182 (0.0 equiv.) in CH.sub.2 Cl.sub.2 (0.5 M) at
 0.degree. C., is added sodium-azide (1.2 equiv.) from Aldrich chemical
 company at 0.degree. C. The reaction is stirred for 1 h and then is
 quenched with saturated ammonium chloride (1.5 mL), diluted with ethyl
 acetate (25 mL), washed with water (2.times.5 mL), brine (1.times.5 mL),
 back-extracted (2.times.), recombined, dried (MgSO.sub.4) and evaporated.
 The compound is purified by flash column chromatography and affords
 compound 183.
 Preparation of 185 (R group=OTES, NPhth or NHAc)
 A solution of 183 (1.0 equivalents) in ethanol (0.01 M total) at 25.degree.
 C. is exposed to 10% Pd(OH).sub.2 --C (0.1 equivalents) and is then
 subsequently capped with a hydrogen balloon at 1 atmosphere. The reaction
 is stirred for 72 hours and is then filtered through celite. The crude
 mixture is subsequently diluted with ether and washed with NaHCO.sub.3
 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography affords compound 185 scheme
 21.
 Preparation of 191
 ##STR76##
 A solution of starting material 190 as disclosed by Schmidt, R. R. et al.
 (Liebigs Ann. Chem. 1987, 825), (1.0 equivalents) is dissolved in a
 mixture of ethanol-tetrahydrofuran-acetic acid (2:1:1), (0.01 M total) at
 25.degree. C. The mixture is next exposed to 10% Pd/C (1.0 equivalents)
 and is then subsequently capped with a hydrogen balloon at 1 atmosphere.
 The reaction is stirred for 72 hours and is then filtered through celite.
 The crude mixture is subsequently diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography (silica, 100%
 ethyl acetate in petroleum ether) affords compound 191. scheme 22 step a.
 Preparation of 192
 ##STR77##
 To a solution of 191 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added tosylchloride (1.2 equivalents) at 0.degree. C. Subsequent
 addition of triethylamine (1.5 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated to afford the crude tosylate. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 192. scheme 22 step b.
 Preparation of 193
 ##STR78##
 To a solution of 192 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added sodium azide from Aldrich chemical company (1.2 equivalents) at
 0.degree. C. Subsequent stirring for 2 hours is followed by dilution with
 diethylether and washing with ammonium chloride (2.times.), brine
 (1.times.) and then MgSO.sub.4. The solution is then concentrated and
 purification by flash column chromatography affords compound 193. scheme
 22 step c.
 Preparation of 194
 ##STR79##
 To solution of 193 in CCl.sub.4 (0.33 M), CH.sub.3 CN (0.33 M) and water
 (0.22 M) at 0.degree. C. is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4
 (4.0 equiv.) and the muddy black mixture is allowed to stir for 1.5 h. The
 mixture is then diluted with ether (25 mL), washed with water (2.times.
 5.0 mL) and brine (1.times. 5 mL). The aqueous layer is back extracted
 (2.times.), recombined, and the organic layer is then dried MgSO.sub.4 and
 evaporated. Purification by flash column chromatography affords the
 compound 194. scheme 22 step d.
 Preparation of 196
 ##STR80##
 A solution of 194 (1.0 equivalents) is dissolved in ethanol (0.01 M total)
 at 25.degree. C. The mixture is next exposed to 10% Pd/C (0.1 equivalents)
 and is then subsequently capped with a hydrogen balloon at 1 atmosphere.
 The reaction is stirred for 72 hours and is then filtered through celite.
 The crude mixture is subsequently diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Next, to a solution of crude amine (1.0 equivalents) in
 methylene chloride (0.10 Molar), is added sodium bicarbonate (2.0
 equivalents) at 0.degree. C. Subsequent addition of 9-fluorenylmethyl
 chloroformate (FMOC-Cl, 1.2 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 196. scheme 22 steps e-f.
 Preparation of 197
 ##STR81##
 To Tetrol 191 (1.0 equivalents) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 197. scheme 22 step g.
 Preparation of 198
 ##STR82##
 To solution of 197 in CCl.sub.4 (0.33 M), CH.sub.3 CN (0.33 M) and water
 (0.22 M) at 0.degree. C. is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4
 (4.0 equiv.) and the muddy black mixture is allowed to stir for 1.5 h. The
 mixture is then diluted with ether (25 mL), washed with water (2.times.
 5.0 mL) and brine (1.times. 5 mL). The crude is then resuspended in a
 mixture of methylene chloride/water (1:1, 0.1 M total) and diazomethane
 (1.2 equivalents) is gradually dropped into the flask via an addition
 funnel at the rate of 1 drop/10 seconds. After complete addition the
 mixture is diluted with ether, washed with brine (2.times.) and the
 aqueous layer is back extracted (2.times.) recombined, and the organic
 layer is then dried MgSO.sub.4 and evaporated. Purification by flash
 column chromatography affords the compound 198. scheme 22 step h.
 Preparation of 200
 ##STR83##
 To a solution of 198 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added a 1.0 M solution of DIBALH in methylene chloride from Aldrich
 chemical company (1.2 equivalents) at 0.degree. C. Subsequent stirring for
 2 hours is followed by dilution with diethylether and washing with
 sodium-potassium tartrate (2.times.), brine (1.times.) and then
 MgSO.sub.4. The solution is then concentrated and purification by flash
 column chromatography affords compound 200. scheme 22 step i.
 Preparation of 201
 ##STR84##
 A solution of 200 (1.0 equivalents) in tetrahydrofuran (0.18 M) is treated
 with DPPA (diphenylphosphorylazide, 2.0 equivalents), triphenylphosphine
 (1.3 equivalents) and DIAD (diisopropyl-azo-dicarboxylate, 1.3
 equivalents). The reaction is heated to 80.degree. C. for 3 hours and then
 diluted with ether (2.times.) and washed with 0.5 M aqueous NaOH
 (2.times.). The organic layer is dried over MgSO.sub.4 and evaporated.
 Purification by flash column chromatography affords compound 201. scheme
 22 step j.
 Preparation of 202
 ##STR85##
 A solution of 201 (1.0 equivalents) is dissolved in ethanol (0.01 M total)
 at 25.degree. C. The mixture is next exposed to 10% Pd/C (0.1 equivalents)
 and is then subsequently capped with a hydrogen balloon at 1 atmosphere.
 The reaction is stirred for 72 hours and is then filtered through celite.
 The crude mixture is subsequently diluted with ether and washed with
 NaHCO.sub.3 (3.times.), brine (1.times.) and dried (MgSO.sub.4) and
 concentrated. Next, to a solution of crude amine (1.0 equivalents) in
 methylene chloride (0.10 Molar), is added sodium bicarbonate (2.0
 equivalents) at 0.degree. C. Subsequent addition of 9-fluorenylmethyl
 chloroformate (FMOC-Cl, 1.2 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 202. scheme 22 step e.
 Preparation of 204
 ##STR86##
 To a solution of 202 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added 10% HCOOH from Aldrich chemical company (1.2 equivalents) at
 0.degree. C. Subsequent stirring for 2 hours is followed by dilution with
 diethylether and washing with sodium bicarbonate (2.times.), brine
 (1.times.) and then MgSO.sub.4. The solution is then resuspended in t-BuOH
 (0.10 M) and pH 7 buffer (0.10 M) and is then exposed to KMnO.sub.4 (1.2
 equivalents) for 2 hours at 0.degree. C. The reaction mixture is next
 washed with sodium bicarbonate (2.times.), brine (1.times.) and then
 MgSO.sub.4. The organic layer is then concentrated and purified by flash
 column chromatography to afford compound 204. scheme 22 step k.
 Preparation of 206
 ##STR87##
 To Tetrol 205 (1.0 equivalents) (as disclosed by Petrus, L. et al. Chem.
 zvesti. 1982, 36, 103) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 206. scheme 23 step a.
 Preparation of 207
 ##STR88##
 To a solution of 206 (1.0 equivalents) in diethylether (0.08 M), is added
 lithiumaluminumhydride (LAH) (1.5 equivalents) at 30.degree. C. The
 reaction is refluxed for 2 hours and then quenched with methanol and
 diluted with ether. The reaction is next worked-up with sodium potassium
 tartrate (2.times.), brine (1.times.) and is then dried (MgSO.sub.4) and
 concentrated. The crude mixture is resuspended in methylene chloride (0.10
 Molar) and to it is added sodium bicarbonate (2.0 equivalents) at
 0.degree. C. Subsequent addition of 9-fluorenylmethyl chloroformate
 (FMOC-Cl, 1.2 equivalents) is followed by stirring for 2 hours and then
 the reaction is diluted with diethylether and washed with ammonium
 chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 207. scheme 23 step b.
 Preparation of 208
 ##STR89##
 To a solution of 207 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added 10% HCOOH (1.1 equivalents). The reaction is stirred at 0.degree.
 C. for 2 minutes and is then diluted with ether and washed with sodium
 bicarbonate (2.times.), brine (1.times.) and then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 208. scheme 23 step c.
 Preparation of 209
 ##STR90##
 To solution of 208 in CCl.sub.4 (0.33 M), CH.sub.3 CN (0.33 M) and water
 (0.22 M) at 20.degree. C. is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4
 (4.0 equiv.) and the muddy black mixture is allowed to stir for 10 min.
 The mixture is then diluted with ether (25 mL), washed with water
 (2.times. 5.0 mL) and brine (1.times. 5 mL). The aqueous layer is back
 extracted (2.times.), recombined, and the organic layer is then dried
 MgSO.sub.4 and evaporated. Purification by flash column chromatography
 affords the compound 209. scheme 23 step d.
 Preparation of 210
 ##STR91##
 To a solution of 205 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added tosylchloride (1.2 equivalents) at 0.degree. C. Subsequent
 addition of triethylamine (1.5 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated to afford the crude tosylate. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 210. scheme 23 step e.
 Preparation of 211
 ##STR92##
 To a solution of 210 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added sodium azide from Aldrich chemical company (1.2 equivalents) at
 0.degree. C. Subsequent stirring for 2 hours is followed by dilution with
 diethylether and washing with ammonium chloride (2.times.), brine
 (1.times.) and then MgSO.sub.4. The solution is then concentrated and
 purification by flash column chromatography affords compound 211. scheme
 23 step f.
 Preparation of 212
 ##STR93##
 To solution of 211 in CCl.sub.4 (0.33 M), CH.sub.3 CN (0.33 M) and water
 (0.22 M) at 20.degree. C. is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4
 (4.0 equiv.) and the muddy black mixture is allowed to stir for 10 min.
 The mixture is then diluted with ether (25 mL), washed with water
 (2.times. 5.0 mL) and brine (1.times. 5 mL). The aqueous layer is back
 extracted (2.times.), recombined, and the organic layer is then dried
 MgSO.sub.4 and evaporated. Purification by flash column chromatography
 affords the compound 212. scheme 23 step g.
 Preparation of 213
 ##STR94##
 A solution of 212 (1.0 equivalents) in ethanol (0.01 M total) at 25.degree.
 C. is exposed to 10% Pd/C (0.1 equivalents) and is then subsequently
 capped with a hydrogen balloon at 1 atmosphere. The reaction is stirred
 for 72 hours and is then filtered through celite. The crude mixture is
 subsequently diluted with ether and washed with NaHCO.sub.3 (3.times.),
 brine (1.times.) and dried (MgSO.sub.4) and concentrated. Purification by
 flash column chromatography affords compound 213. scheme 23 step h.
 Preparation of 214
 ##STR95##
 Compound 213 is suspended in methylene chloride (0.10 Molar) and to it is
 added sodium bicarbonate (2.0 equivalents) at 0.degree. C. Subsequent
 addition of 9-fluorenylmethyl chloroformate (FMOC-Cl, 1.2 equivalents) is
 followed by stirring for 2 hours and then the reaction is diluted with
 diethylether and washed with ammonium chloride (2.times.), brine
 (1.times.) and then dried (MgSO.sub.4) and concentrated. Purification by
 flash column chromatography affords compound 214. scheme 23 step i.
 Preparation of 215
 ##STR96##
 To a solution of 205 (1.0 equivalents) in pyridine (0.10 Molar), is added
 trimethylacetyl chloride (pivaloyl chloride) (2.5 equivalents) at
 0.degree. C. The reaction is stirred for 2 hours and then diluted with
 diethylether and washed with ammonium chloride (2.times.), copper sulfate
 (2.times.), brine (1.times.), dried over MgSO.sub.4 and concentrated. Next
 a solution of the crude intermediate (1.0 equivalents) is dissolved in
 methylene chloride (0.10 Molar) and diisopropylethylamine (3.3
 equivalents) is added at 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 215. scheme 23 step j.
 Preparation of 216
 ##STR97##
 To solution of 215 in CCl.sub.4 (0.33 M), CH.sub.3 CN (0.33 M) and water
 (0.22 M) at 20.degree. C. is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4
 (4.0 equiv.) and the muddy black mixture is allowed to stir for 10 min.
 The mixture is then diluted with ether (25 mL), washed with water
 (2.times. 5.0 mL) and brine (1.times. 5 mL). The aqueous layer is back
 extracted (2.times.), recombined, and the organic layer is then dried
 MgSO.sub.4 and evaporated. The crude is then resuspended in a mixture of
 methylene chloride/water (1:1, 0.1 M total) and diazomethane (1.2
 equivalents) is gradually dropped into the flask via an addition funnel at
 the rate of 1 drop/10 seconds. After complete addition the mixture is
 diluted with ether, washed with brine (2.times.) and the aqueous layer is
 back extracted (2.times.) recombined, and the organic layer is then dried
 MgSO.sub.4 and evaporated. Purification by flash column chromatography
 affords the compound 216. scheme 23 step k.
 Preparation of 217
 ##STR98##
 To a solution of 216 (1.0 equivalents) in methylene chloride (0.10 Molar)
 is added a 1.0 M solution of DIBALH in methylene chloride from Aldrich
 chemical company (1.2 equivalents) at 0.degree. C. Subsequent stirring for
 2 hours is followed by dilution with diethylether and washing with
 sodium-potassium tartrate (2.times.), brine (1.times.) and then
 MgSO.sub.4. The solution is then concentrated and purification by flash
 column chromatography affords compound 217. scheme 23 step l.
 Preparation of 218
 ##STR99##
 To 217 (1.0 equivalents) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (1.1 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Purification by flash
 column chromatography affords compound 218. scheme 23 step m.
 Preparation of 220
 ##STR100##
 To a solution of 218 (1.0 equivalents) in diethylether (0.08 M), is added
 lithiumaluminumhydride (LAH) (1.5 equivalents) at 30.degree. C. The
 reaction is refluxed for 2 hours and then quenched with methanol and
 diluted with ether. The reaction is next worked-up with sodium potassium
 tartrate (2.times.), brine (1.times.) and is then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 220. scheme 23 step n.
 Preparation of 221
 ##STR101##
 To Tetrol 205 (1.0 equivalents) in pyridine (0.10 Molar), is added
 dimethyoxytritylchloride (DMT chloride) (2.5 equivalents) at 0.degree. C.
 The reaction is stirred for 2 hours and then diluted with diethylether and
 washed with ammonium chloride (2.times.), copper sulfate (2.times.), brine
 (1.times.), dried over MgSO.sub.4 and concentrated. Next a solution of the
 crude intermediate (1.0 equivalents) is dissolved in methylene chloride
 (0.10 Molar) and diisopropylethylamine (3.3 equivalents) is added at
 0.degree. C. Subsequent addition of triethylsilyl
 trifluoromethanesulfonate (3.3 equivalents) is followed by stirring for 2
 hours and then the reaction is diluted with diethylether and washed with
 ammonium chloride (2.times.), brine (1.times.) and then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography affords
 compound 221. scheme 23 step a.
 Preparation of 222
 ##STR102##
 To solution of 221 in CCl.sub.4 (0.33 M), CH.sub.3 CN (0.33 M) and water
 (0.22 M) at 20.degree. C. is added RuCl.sub.3 (0.03 equiv.) and NaIO.sub.4
 (4.0 equiv.) and the muddy black mixture is allowed to stir for 10 min.
 The mixture is then diluted with ether (25 mL), washed with water
 (2.times. 5.0 mL) and brine (1.times. 5 mL). The aqueous layer is back
 extracted (2.times.), recombined, and the organic layer is then dried
 MgSO.sub.4 and evaporated. Purification by flash column chromatography
 affords the compound 222. scheme 23 step o.
 Preparation of 224
 ##STR103##
 To a solution of 222 (1.0 equivalents) in diethylether (0.08 M), is added
 lithiumaluminumhydride (LAH) (1.5 equivalents) at 30.degree. C. The
 reaction is refluxed for 2 hours and then quenched with methanol and
 diluted with ether. The reaction is next worked-up with sodium potassium
 tartrate (2.times.), brine (1.times.) and is then dried (MgSO.sub.4) and
 concentrated. Purification by flash column chromatography affords compound
 224. scheme 23 step p.
 Preparation of 216
 To a stirred solution of the acid 214 (1.0 equivalents) in
 dimethylformamide (0.10 Molar) at 25.degree. C., is added
 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Next
 dicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction is
 stirred for 1 hour in the presence of an appropriately substituted solid
 support (N-(2-Aminoethyl)-3-amino-propyl glass; aminopolystyrene resin;
 aminopropyl glass; isothiocyanato glass, all with or without a linker
 extending from the amino group on the support etc. from Sigma Company).
 The mixture is then diluted with ether, filtered and the filtrate is
 washed with aqueous NaHCO.sub.3 (2.times.), water (2.times.), and brine
 (2.times.). The organic phase is dried over MgSO.sub.4 and then
 concentrated.
 Preparation of 226; 228; 230 or 232
 To a stirred solution of the acid 214; 62; 215 or 62 (1.0 equivalents) and
 the amine 216; 226; 228 or 230 (1.1 equivalents) in dimethylformamide
 (0.10 Molar) at 25.degree. C., is added 1-hydroxybenzotriazole (HOBT; 1.1
 equivalents). Next dicyclohexylcarbodiimide (1.2 equivalents) is added and
 the reaction is stirred for 14 hours. The mixture is diluted with ether,
 filtered and the filtrate is washed with aqueous NaHCO.sub.3 (2.times.),
 water (2.times.), and brine (2.times.). The organic phase is dried over
 MgSO.sub.4 and then concentrated. Purification by flash column
 chromatography and then reexposure of the intermediate compound (1.0
 equivalents) in dimethyl-formamide (0.10 Molar) at 25.degree. C., is added
 piperidine (1.1 equivalents). The reaction is stirred for 1 hour and is
 then diluted with ether, and washed with aqueous CuSO.sub.4 (2.times.),
 water (2.times.), and brine (2.times.). The organic phase is dried over
 MgSO.sub.4 and then concentrated. Purification by flash column
 chromatography affords compound 226; 228; 230 or 232, respectively. scheme
 24.
 Preparation of 234
 To a stirred solution of 232 (1.0 equivalents) in acetonitrile (0.50 Molar)
 is added an HF-pyridine solution (0.50 M) from Aldrich chemical company.
 The reaction is allowed to stir for five hours and is then condensed. The
 crude 234 oligomer is then resuspended in p-dioxane (0.50 Molar) to which
 is added a 3.0 Molar solution of NaOH (3.0 equivalents). The reaction is
 stirred for 1 hour at 50.degree. C. and is then quenched with aqueous
 NH.sub.4 Cl (2.times.) and subsequently lyophilized. Purification by HPLC
 chromatography affords compound 234. scheme 24.
 Preparation of Peptoid Combinatorial Libraries
 Scheme 500
 A depiction of the generation of a combinatorial library for oligopeptoid
 compounds is shown in scheme 500. The example uses an alphabet of eight
 D-aldose hexose sugars (other sugars groups such as the D/L ketoses and
 L-configurations of aldose hexoses, may be used) and carries the synthesis
 to a degree of three or 512 compounds. (The process can repeat itself to
 afford the library of desired size). Standard chemistry is shown and
 follows the reaction conditions as described above herein for peptoid
 synthesis. The solid support used is the standard
 N-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;
 aminopropyl glass; isothiocyanato glass and others as purchased from Sigma
 company. All supports may be with or without a linker extending from the
 amino group on the support (eg. succinate linkage, amide, ether, alkyl
 chain with terminal carbon activated as free alcohol, bromide etc.).
 ##STR104##
 ##STR105##
 ##STR106##
 ##STR107##
 ##STR108##
 ##STR109##
 Preparation of Nucleotoid Combinatorial libraries
 Scheme 550
 A depiction of the generation of a combinatorial library for
 oligonucleotoid compounds is shown in scheme 550. The example uses an
 alphabet of eight D-aldose hexose sugars (other sugars groups such as the
 D/L ketoses and L-configurations of aldose hexoses, may be used) and
 carries the synthesis to a degree of three or 512 compounds. (The process
 can repeat itself to afford the library of desired size). Standard
 chemistry is shown and follows the reaction conditions as described above
 herein for carbonucleotoid synthesis. The solid support used is the
 standard N-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene
 resin; aminopropyl glass; isothiocyanato glass and others as purchased
 from Sigma company. All supports may be with or without a linker extending
 from the amino group on the support (eg. succinate linkage, amide, ether,
 alkyl chain with terminal carbon activated as free alcohol, bromide etc.).
 Preparation of Compound 2000
 To a solution of 76 (1.0 equiv) was added methylene chloride (0.1 M) and
 benzaldehyde (1.1 equiv), and the solution was exposed to ZnCl (1.1 equiv)
 at 25.degree. C. and allowed to stir for 2.5 hour. The solution is then
 diluted with ether and then washed with a saturated solution of sodium
 bicarbonate (2.times.), water (2.times.), brine (1.times.) and then dried
 over MgSO.sub.4. The compound is purified by flash column chromatography
 to yield the desired benzylidene.
 ##STR110##
 2. Connection of the C-2 differentiated sugar to a solid support
 ##STR111##
 The benzylidene is then azeotroped with benzene (2.times.100 mL) and then
 dried overnight under vacuum over P.sub.2 O.sub.5. A mixture of
 benzylidene, dibutyl tin oxide (1.2 equiv.) and dry methanol (0.25 M) are
 heated at reflux for 4 h until the solution became clear and homogeneous.
 (An automatic stirring apparatus may be necessary.) The solvent is next
 removed in vacuo to give a foamy white tin complex which was then
 azeotroped with benzene (2.times.) and dried (2 h to overnight) under
 vacuum over P.sub.2 O.sub.5. Next, anhydrous DMF (0.2M) is added to
 redissolve the tin complex and then CsF (1.2 equiv.) and finally Benzyl
 bromide (1.5 equiv.) are added and then heated (40.degree. C.) overnight.
 The clear solution is partially distilled under vacuum, (3.3 mm Hg,
 75-100.degree. C.) to obtain 1/5 the original volume of solvent. Reaction
 mixture was then diluted with ethyl acetate (2 L) and washed with a small
 amount of water (2.times.) to remove cesium salts. Aqueous layer is back
 extracted with ethyl acetate (3.times.) and then recombined with the
 organic layer which was then dried over MgSO.sub.4 and evaporated.
 Purification by flash column chromatography yields the desired benzyl
 ether 2000. For related chemistry see Nagashima, N.; Ohno, M. Chemistry
 Letters, Chem. Soc. of Japan 1987, 141.
 Preparation of Compound 2010
 Procedure adopted from Johansson R.; Samuelsson; B. J. Chem. Soc., Chem.
 Commun., 1984, 201. To a solution of the benzylidene acetal (1 equiv) and
 sodium cyanoborohydride (5 equiv.) in DMF (0.125 M) containing powdered 3
 angstrom molecular sieves is added trifluoroacetic acid (10 equiv) and the
 reaction is allowed to stir at 0.degree. C. until no starting material
 remains. Reaction mixture is then diluted with ethyl acetate (2 L) and
 washed with a small amount of water (2.times.) and brine (2.times.).
 Aqueous layer is back extracted with ethyl acetate (3.times.) and then
 recombined with the organic layer which was then dried over MgSO.sub.4 and
 evaporated. Purification by flash column chromatography yields the desired
 benzyl ether 2010.
 Preparation of Compound 2020
 To a solution of 2010 (1.0 equiv) was added methylene chloride (0.1 M) and
 benzaldehyde ( 1.1 equiv), and the solution was exposed to ZnCl (1.1
 equiv) at 25.degree. C. and allowed to stir for 2.5 hour. The solution is
 then diluted with ether and then washed with a saturated solution of
 sodium bicarbonate (2.times.), water (2.times.), brine (1.times.) and then
 dried over MgSO.sub.4. The compound is purified by flash column
 chromatography to yield the desired benzylidene 2020.
 Preparation of Compound 2030
 To a solution of alcohol 2020 (22.0 g, 0.1068 mol, 1.0 equiv.) in THF (0.5
 M) at 0.degree. C., is added NaH (1.0 equiv., 35% dispersion in mineral
 oil) over several portions. The reaction mixture is warmed to room
 temperature and stirred 1 h. Next, the reaction is cooled to 0.degree. C.
 and treated with benzyl bromide (1.0 equiv.) and stirred for 1.5 h. A
 saturated solution of ammonium chloride (50 mL) is added dropwise to
 quench the reaction mixture at 0.degree. C. and the mixture was diluted
 with ethyl acetate, washed with water (2.times.), brine (1.times.), dried
 over MgSO.sub.4 and evaporated. Purification by flash column
 chromatography yields tribenzyl ether 2030.
 Preparation of Compound 2040
 Procedure as adopted from Hanessian S.; Organic Syntheses 19 8 7, 243. To a
 suspension containing 1.0 equivalent of benzylidene 2030 in one molar
 carbon tetrachloride and 1,1,2,2-tetrachloroethane (1.5 equivalent) is
 added 1.2 equivalents of N-bromosuccinimide and 0.5 equivalents of barium
 carbonate. The resulting suspension is heated at the reflux temperature of
 the mixture with mechanical stirring for a period of 2.5 hour and filtered
 while hot. The solution is washed with water (3.times.), then dried over
 anhydrous sodium sulfate and evaporated. Purification by flash column
 chromatography yields tribenzyl ether 2040.
 Preparation of Compound 2050
 To a solution of 2040 (1.0 equivalents) in methylene chloride (0.10 M), is
 added diisopropylethylamine (4.0 equivalents) at 25.degree. C. The
 reaction is stirred for 5 minutes and then
 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv) is added,
 as prepared from the procedures of Sinha et al. Nucl. Acids Res. 1984, 12,
 4539. After 15 minutes the reaction is
 Synthesis of a C1-C2-Phosophodiester oligomer using a solid support
 ##STR112##
 brine (1.times.) and is then dried (MgSO.sub.4) and concentrated.
 Purification by flash column chromatography (silica, 30% ethyl acetate in
 petroleum ether) affords compound 2050 (as shown in scheme 2000).
 Preparation of Compound 2060
 To a solution of alcohol 2040 (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (1.0 equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and exposed to the solid
 support functionalized with a bromide linker or any reasonable leaving
 group attached (1.0 equiv.) and stirred for 2 hours. A saturated solution
 of ammonium chloride (50 mL) is added dropwise to quench the reaction
 mixture at 0.degree. C. and the support was washed with ethyl acetate, 1%
 NaOH in methanol (2.times.) to remove the benzoate and finally brine
 (1.times.) to give 2060. The solid support used is the standard
 N-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;
 aminopropyl glass; isothiocyanato glass and others as purchased from Sigma
 company. All supports may be with or without a linker extending from the
 amino group on the support (eg. succinate linkage, amide, ether, alkyl
 chain with terminal carbon activated as free alcohol, bromide etc.).
 1. Synthesis of a C-3 differentiated sugar
 ##STR113##
 2. Connection of the C-3 differentiated sugar to a solid support
 ##STR114##
 Preparation of Compound 2070
 To a solution of 76 (1.0 equiv) was added methylene chloride (0.1 M) and
 benzaldehyde ( 1.1 equiv), and the solution was exposed to ZnCl (1.1
 equiv) at 25.degree. C. and allowed to stir for 2.5 hour. The solution is
 then diluted with ether and then washed with a saturated solution of
 sodium bicarbonate (2.times.), water (2.times.), brine (1.times.) and then
 dried over MgSO.sub.4. The compound is purified by flash column
 chromatography to yield the desired benzylidene. Procedure adopted from
 Johansson R.; Samuelsson; B. J. Chem. Soc., Chem. Commun., 1984, 201. To a
 solution of the benzylidene acetal (1 equiv) and sodium cyanoborohydride
 (5 equiv.) in DMF (0.125 M) containing powdered 3 angstrom molecular
 sieves is added trifluoroacetic acid (10 equiv) and the reaction is
 allowed to stir at 0.degree. C. until no starting material remains.
 Reaction mixture is then diluted with ethyl acetate (2 L) and washed with
 a small amount of water (2.times.) and brine (2.times.). Aqueous layer is
 back extracted with ethyl acetate (3.times.) and then recombined with the
 organic layer which was then dried over MgSO.sub.4 and evaporated.
 Purification by flash column chromatography yields the desired benzyl
 ether 2070.
 Preparation of Compound 2080
 To a solution of 2070 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added triethylamine (1.1 equivalents) at 0.degree. C. Subsequent
 addition of tertbutyldiphenylsilylchloride (1.1 equivalents) is followed
 by stirring for 2 hours and then the reaction is diluted with diethylether
 and washed with ammonium chloride (2.times.), brine (1.times.) and then
 dried (MgSO.sub.4) and concentrated. Purification by flash column
 chromatography affords the TBDPS ether which is subsequently carried on as
 follows:
 The TBDPS ether is then azeotroped with benzene (2.times.100 mL) and then
 dried overnight under vacuum over P.sub.2 O.sub.5. A mixture of
 benzylidene, dibutyl tin oxide (1.2 equiv.) and dry methanol (0.25 M) are
 heated at reflux for 4 h until the solution became clear and homogeneous.
 (An automatic stirring apparatus may be necessary.) The solvent is next
 removed in vacuo to give a foamy white tin complex which was then
 azeotroped with benzene (2.times.) and dried (2 h to overnight) under
 vacuum over P.sub.2 O.sub.5. Next, anhydrous DMF (0.2M) is added to
 redissolve the tin complex and then CsF (1.2 equiv.) and finally Benzoyl
 bromide for the benzoate formation, (1.5 equiv.) are added and then heated
 (40.degree. C.) overnight. The clear solution is partially distilled under
 vacuum, (3.3 mm Hg, 75-100.degree. C.) to obtain 115 the original volume
 of solvent. Reaction mixture was then diluted with ethyl acetate (2 L) and
 washed with a small amount of water (2.times.) to remove cesium salts.
 Aqueous layer is back extracted with ethyl acetate (3.times.) and then
 recombined with the organic layer which was then dried over MgSO.sub.4 and
 evaporated. Purification by flash column chromatography yields the desired
 benzyl ether 2080. For related chemistry see Nagashima, N.; Ohno, M.
 Chemistry Letters, Chem. Soc. of Japan 1987, 141.
 Preparation of Compound 2090
 To a solution of alcohol 2080 (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (1.0 equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and treated with benzyl
 bromide (1.0 equiv.) and stirred for 1.5 h. The compound is then treated
 with tetrabutylammonium fluoride (2.0 equivalents) and allowed to stir for
 an additional 2 hours. A saturated solution of ammonium chloride (50 mL)
 is then added dropwise to quench the reaction mixture at 0.degree. C. and
 the mixture was diluted with ethyl acetate, washed with water (2.times.),
 brine (1.times.), dried over MgSO.sub.4 and evaporated. Purification by
 flash column chromatography yields tribenzyl ether 2090.
 Preparation of Compound 2100
 To a solution of 2090 (1.0 equivalents) in methylene chloride (0.10 M), is
 added diisopropylethylamine (4.0 equivalents) at 25.degree. C. The
 reaction is stirred for 5 minutes and then
 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv) is added,
 as prepared from the procedures of Sinha et al. Nucl. Acids Res. 1984, 12,
 4539. After 15 minutes the reaction is complete and is next diluted with
 ether and next washed with brine (1.times.) and is then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography (silica, 30%
 ethyl acetate in petroleum ether) affords compound 2100 (as shown in
 scheme 2002).
 Synthesis of a C1-C3-Phosophodiester oligomer using a solid support
 ##STR115##
 Preparation of Compound 2110
 To a solution of alcohol 2090 (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (1.0 equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and exposed to the solid
 support functionalized with a bromide linker or any reasonable leaving
 group attached (1.0 equiv.) and stirred for 2 hours. A saturated solution
 of ammonium chloride (50 mL) is added dropwise to quench the reaction
 mixture at 0.degree. C. and the support was washed with ethyl acetate, 1%
 NaOH in methanol (2.times.) to remove the benzoate and finally brine
 (1.times.) to give 2110. The solid support used is the standard
 N-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;
 aminopropyl glass; isothiocyanato glass and others as purchased from Sigma
 company. All supports may be with or without a linker extending from the
 amino group on the support (eg. succinate linkage, amide, ether, alkyl
 chain with terminal carbon activated as free alcohol, bromide etc.).
 Preparation of Compound 2120
 To a solution of 76 (1.0 equiv) was added methylene chloride (0.1 M) and
 benzaldehyde (1.1 equiv), and the solution was exposed to ZnCl (1.1 equiv)
 at 25.degree. C. and allowed to stir for 2.5 hour. The solution is then
 diluted with ether and then washed with a saturated solution of sodium
 bicarbonate (2.times.), water (2.times.), brine (1.times.) and then dried
 over MgSO.sub.4. The compound is purified by flash column chromatography
 to yield the desired
 1. Synthesis of a C-4 differentiated sugar
 ##STR116##
 2. Connection of the C-4 differentiated sugar to a solid support
 ##STR117##
 benzylidene and carried on as follows:
 To a solution of benzylidene (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (1.0 equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and treated with benzyl
 bromide (1.0 equiv.) and stirred for 1.5 h. A saturated solution of
 ammonium chloride (50 mL) is then added dropwise to quench the reaction
 mixture at 0.degree. C. and the mixture was diluted with ethyl acetate,
 washed with water (2.times.), brine (1.times.), dried over MgSO.sub.4 and
 evaporated. Purification by flash column chromatography yields tribenzyl
 ether 2120.
 Preparation of Compound 2130
 Procedure adopted from Johansson R.; Samuelsson; B. J. Chem. Soc., Chem.
 Commun., 1984, 201. To a solution of the benzylidene acetal 2120 (1 equiv)
 and sodium cyanoborohydride (5 equiv.) in DMF (0.125 M) containing
 powdered 3 angstrom molecular sieves is added trifluoroacetic acid (10
 equiv) and the reaction is allowed to stir at 0.degree. C. until no
 starting material remains. Reaction mixture is then diluted with ethyl
 acetate (2 L) and washed with a small amount of water (2.times.) and brine
 (2.times.). Aqueous layer is back extracted with ethyl acetate (3.times.)
 and then recombined with the organic layer which was then dried over
 MgSO.sub.4 and evaporated. Purification by flash column chromatography
 yields the desired benzyl ether 2130.
 Preparation of Compound 2140
 To a solution of 2130 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added triethylamine (1.1 equivalents) at 0.degree. C. Subsequent
 addition of tertbutyldiphenylsilylchloride (1.1 equivalents) is followed
 by stirring for 2 hours and then the reaction is diluted with diethylether
 and washed with ammonium chloride (2.times.), brine (1.times.) and then
 dried (MgSO.sub.4) and concentrated. Purification by flash column
 chromatography affords the TBDPS ether which is subsequently carried on as
 follows:
 To a solution of TBDPS ether (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (1.0 equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and treated with benzoyl
 bromide to afford benzoate formation (1.0 equiv.) and stirred for 1.5 h. A
 saturated solution of ammonium chloride (50 mL) is then added dropwise to
 quench the reaction mixture at 0.degree. C. and the mixture was diluted
 with ethyl acetate, washed with water (2.times.), brine (1.times.), dried
 over MgSO.sub.4 and evaporated. Purification by flash column
 chromatography yields tribenzyl ether 2140.
 Preparation of Compound 2150
 The compound 2140 is then treated with tetrabutylammonium fluoride (2.0
 equivalents) in THF (0.1 Molar) and allowed to stir for an additional 2
 hours at 25.degree. C. A saturated solution of ammonium chloride (50 mL)
 is then added dropwise to quench the reaction mixture at 0.degree. C. and
 the mixture was diluted with ethyl acetate, washed with water (2.times.),
 brine (1.times.), dried over MgSO.sub.4 and evaporated. Purification by
 flash column chromatography yields tribenzyl ether 2150.
 Preparation of Compound 2160
 To a solution of 2150 (1.0 equivalents) in methylene chloride (0.10 M), is
 added diisopropylethylamine (4.0 equivalents) at 25.degree. The reaction
 is stirred for 5 minutes and then
 2-cyanoethyl-N,N-diisopropyl-chlorophosphoramidite (1.5 equiv) is added,
 as prepared from the procedures of Sinha et al. Nucl. Acids Res. 1984, 12,
 4539. After 15 minutes the reaction is complete and is next diluted with
 ether and next washed with brine (1.times.) and is then dried (MgSO.sub.4)
 and concentrated. Purification by flash column chromatography (silica, 30%
 ethyl acetate in petroleum ether) affords compound 2160 (as shown in
 scheme 2004).
 Preparation of Compound 2170
 To a solution of alcohol 2150 (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (1.0 equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and exposed to the solid
 support functionalized with a bromide linker or any reasonable leaving
 group attached (1.0 equiv.)
 Synthesis of a C1-C4-Phosophodiester oligomer using a solid support
 ##STR118##
 and stirred for 2 hours. A saturated solution of ammonium chloride (50 mL)
 is added dropwise to quench the reaction mixture at 0.degree. C. and the
 support was washed with ethyl acetate, 1% NaOH in methanol (2.times.) to
 remove the benzoate and finally brine (1.times.) to give 2170. The solid
 support used is the standard N-(2-Aminoethyl)-3-amino-propyl glass
 support; amino-polystyrene resin; aminopropyl glass; isothiocyanato glass
 and others as purchased from Sigma company. All supports may be with or
 without a linker extending from the amino group on the support (eg.
 succinate linkage, amide, ether, alkyl chain with terminal carbon
 activated as free alcohol, bromide etc.).
 Preparation of Compound 3010
 Procedure as described in Methods in Carbohydrate chemistry, Whistler, R.,
 II, 1963, p. 327. A mixture of 80 g anhydrous D-glucosamine hydrochloride
 or D-galactosamine hydrochloride from Aldrich chemical company, in 200 mL.
 methanol and 20 g Dowex 50 (H+) acidic resin, is stirred at the boiling
 point in a round bottom flask. After 24-hr. reaction time, the resin is
 removed by filtration and ished three times with 20 ml. of methanol. The
 filtrate and washings are combined and concentrated to about 125 ml by
 rotovap. The concentrate is allowed to cool to room temperature and the
 product crystallizes overnight and carried on as follows:
 The methyl glycoside is dissolved in chloroform (0.5 M) and to it, is added
 phthalic anhydride (1.5 equiv.) and the reaction mixture is allowed to
 reflux at 70.degree. C. for 4 h. The product
 1. C-2 differentiated amine derivative
 ##STR119##
 2. Connection of a C-2 differentiate amine sugar to a solid support
 ##STR120##
 3010 is then crystallized and carried onto the next step.
 Preparation of Compound 3020
 To a solution of alcohol 3010 (1.0 equiv.) in THF (0.5 M) at 0.degree. C.,
 is added NaH (3.3equiv., 35% dispersion in mineral oil) over several
 portions. The reaction mixture is warmed to room temperature and stirred 1
 h. Next, the reaction is cooled to 0.degree. C. and treated with benzyl
 bromide (3.3 equiv.) and stirred for 1.5 h. A saturated solution of
 ammonium chloride (50 mL) is then added dropwise to quench the reaction
 mixture at 0.degree. C. and the mixture was diluted with ethyl acetate,
 washed with water (2.times.), brine (1.times.), dried over MgSO.sub.4 and
 evaporated. Purification by flash column chromatography yields tribenzyl
 ether and is carried on as follows:
 To a solution of tribenzyl ether in nitromethane is added trimethylsilyl
 cyanide (3.0 equivalents) and then SnCl.sub.4 (0.02 equivalents). The
 mixture is stirred for one hour and then an aqueous solution of sodium
 acetate was added to hydrolyze the remaining trimethylsilyl cyanide. The
 mixture is evaporated and the remaining oil is resuspended in
 dichloromethane and washed with sodium acetate solution (1.times.), water
 (1.times.), brine (1.times.) and then dried over magnesium sulphate and
 concentrated. The crude solid is then recrystallized from methanol is next
 dissolved in ethanol (0.15 M) and then concentrated H.sub.2 SO.sub.4 (0.01
 equivalents-catalytic) is added. The reaction mixture is heated to
 85.degree. C. for eight hours. The solution is next concentrated in vacuo
 and purification by flash column chromatography affords compound 3020
 scheme 3000.
 Preparation of Compound 3030
 To a solution of 3020 (1.0 equivalents) in methylene chloride (0.10 Molar),
 is added potassium carbonate (2.0 equivalents) at 0.degree. C. Subsequent
 addition of 9-fluorenylmethyl chloroformate (FMOC-Cl, 1.2 equivalents) is
 followed by stirring for 2 hours and then the reaction is diluted with
 diethylether and washed with ammonium chloride (2.times.), brine
 (1.times.) and then dried (MgSO.sub.4) and concentrated. Purification by
 flash column chromatography affords product which is carried on as
 follows:
 To a solution of ester in ethanol (0.13 Molar), is added sodium ethoxide
 (0.3 equivalents) and the reaction mixture is stirred for two hours at
 room temperature. The solution is then concentrated in vacuo and
 purification by flash column chromatography affords compound 3030 scheme
 3000.
 Preparation of Compound 3040
 To a stirred solution of the acid 3030 (1.0 equivalents) and the (1.1
 equivalents) in dimethylformamide (0.10 Molar) at 25.degree. C., is added
 1-hydroxybenzotriazole (HOBT; 1.1 equivalents). Next
 dicyclohexylcarbodiimide (1.2 equivalents) is added and the reaction is
 stirred for 2 hours. The mixture is then exposed to the solid support and
 mixed for 24 hours. (The solid support used is the standard
 N-(2-Aminoethyl)-3-amino-propyl glass support; amino-polystyrene resin;
 aminopropyl glass; isothiocyanato glass and others as purchased from Sigma
 company. All supports may be with or without a linker extending from the
 amino group on the support (eg. succinate linkage, amide, ether, alkyl
 chain with terminal carbon activated as free alcohol, bromide etc.)). The
 mixture is then diluted with ether, washed with aqueous NaHCO.sub.3
 (2.times.), water (2.times.), and brine (2.times.). Next, the
 compound/support (1.0 equivalents) in dimethyl-formamide (0.10 Molar) at
 25.degree. C., is added piperidine (1.1 equivalents). The support is
 stirred or exposed for 1 hour and is then diluted with ether, and washed
 with aqueous CuSO.sub.4 (2.times.), water (2.times.), and brine
 (2.times.). The final step affords compound 3040.
 ##STR121##
 Physical Data for Scheme 9
 Phosphoramidate 138 (2 diastereomers): IR, (neat) cm.sup.-1 : 3089, 2964,
 2927, 2856, 2253, 1497, 1455, 1396, 1363, 1253, 1184, 1156, 1094, 1028,
 978, 876, 836, 779, 735, .sup.1 H-NMR (400 MHz, C.sub.6 D.sub.6): .delta.
 7.34 (m, 5H, Ph), 7.14 (m, 10H, Ph), 497 (m, 4H, CH.sub.2 Ph), 4.78 (m,
 2H, CH.sub.2 Ph), 4.07-3.24 (m, 13H, OCH, OCH.sub.2, CH.sub.2 CN), 1.81
 (m, 2H, CH(CH.sub.3).sub.2), 1.16 (m, 12H, CH.sub.3 CH), 1.03, 1.02 (2 s,
 9H, .sup.1 BuSi), 0.20, 0.18, 0.16, 0.15, (4 s, 6H, Me.sub.2 Si); HRMS:
 C.sub.43 H.sub.63 O.sub.7 N.sub.2 PSi, Calc. (M+Cs.sup.+): 911.3197;
 found: 911.3185.
 Naphthoylester .sup.136 IR, (neat) cm.sup.-1 : 3494, 3062, 2919, 1716,
 1630, 1600, 1454, 1355, 1284, 1228, 1197, 1091, 779, 736; .sup.1 H-NMR
 (250 MHz, CDCI.sub.3): .delta. 8.58 (s, 1H, Ar), 8.00 (m, 2H, Ar), 7.89
 (m, 2H, Ar), 7.59 (m, 2H, Ar), 7.32 (m, 15H, Ph), 4.95 (m, 3H), 4.90 (d,
 J=4.5 Hz, 1H), 4.69 (m, 3H), 4.52 (dd, J=3.9, 12.0 Hz, 1H), 3.91 (dd
 J=2.6, 12.0, 1H), 3.83 (d, J=8.3, 1H), 3.70 (m, 4H), 3.96 (m, 1H), 2.25
 (s, 1H, OH). HRMS: C.sub.39 H.sub.38 O.sub.7 Calc. (M+Cs.sup.+): 751.1672;
 found: 751.1668.
 Dimer .sup.142 IR, (neat) cm.sup.-1 : 3397, 3030, 2923, 2254, 1718, 1653,
 1629, 1497, 1453, 1355, 1284, 1227, 1197, 1094, 1029, 780. .sup.1 H-NMR
 (400 MHz, C.sub.6 D.sub.6): .delta. 8.82 (3, 1H, Ar), 8.26 (d, 1H, Ar),
 7.72 (m, 1H, Ar), 7.61 (m, 1H, Ar), 7.48 (m, 1H, Ar), 7.37-6.95 (m, 32H,
 Ar, Ph), 4.89-4.18 (m, 21H, CH.sub.2 Ph, CH.sub.2 --Ar, --CH.sub.2
 CH.sub.2 CN, CHCH.sub.2 --Ar and CH.sub.2 OH), 3.95-3.45 (m, 13H, CH-- and
 CH.sub.2 -sugar), 1.71 (s, 1H, OH); HRMS: C.sub.170 H.sub.72 O.sub.5 NP
 calc. (M+H.sup.+): 1198.4718; found: 1198.4715.
 Tetramer .sup.150 IR, (neat) cm.sup.-1 : 3420, 3064, 2924, 2255, 1721,
 1497, 1455, 1357, 1278, 1028, 737. .sup.1 H-NMR (400 MHz, CDCI.sub.3):
 .delta.8.41 (s, 1H, Ar), 8.00 (m, 2H, Ar), 7.91 (m, 2H, Ar), 7.55 (m, 2H,
 Ar), 7.30 (m, 60H, Ph), 4.93-4.05 (m, 39H, CH.sub.2 Ph, CH.sub.2 --Ar,
 CH.sub.2 CH.sub.2 CN and CH.sub.2 OH), 3.88-3.27 (m, 23H, CH-- and
 CH.sub.2 -sugar), 2.58 (s, 1H, OH). HRMS: C.sub.132 H.sub.140 O.sub.31
 N.sub.3 P.sub.3 Calc. (M+Cs.sup.+) 2488.7738; found: 2488.7758.
 Tetramer .sup.154 IR, (neat) cm.sup.-1 : 3376, 2934, 1450, 1244, 1110,
 1088. .sup.1 H-NMR (400 MHz, D.sub.2 O): .delta. 8.41 (s, 1H, Ar), 8.00
 (m, 2H, Ar), 7.91 (m, 2H, Ar), 7.55 (m, 2H, Ar), 4.93-4.05 (m, 4H,
 CH.sub.2 --Ar and CH.sub.2 OH), 3.88-3.27 (m, 32H, CH-- and CH.sub.2
 -sugar); HRMS: C.sub.39 H.sub.59 O.sub.31 P.sub.3 Calc. (M+H.sup.+):
 1117.2331; found: 1117.2350.