The pyrimidine compounds of the present invention are represented by the following formula: ##STR1## and pharmaceutically acceptable salts thereof, wherein, R.sup.1 represents a hydroxyl or an amino which may be substituted by an acyl group; R.sup.2 represents a hydrogen atom or an alkyl having 1 to 4 carbons; R.sup.3 represents a hydrogen or a hydroxyl; and R.sup.4 and R.sup.5 each represent a hydrogen or together form a group --R.sup.6 R.sup.7 Si--O--SiR.sup.6' R.sup.7' --, wherein R.sup.6, R.sup.7, R.sup.6' and R.sup.7' are the same or different from one another and each represent an alkyl having 1 to 4 carbons. The compounds of the present invention exhibit an excellent antitumor effect.

TECHNICAL FIELD 
The present invention relates to novel pyrimidine nucleoside derivatives 
having excellent antitumor activities. 
BACKGROUND ART 
As the commercially available antitumor agents of pyrimidine series 
metabolism antagonistic agents, 5-fluorouracil (Duschinsky, R., et al., J. 
Am. Chem. Soc., 79, 4559 (1957)), Tegafur (Hiller, SA., et al., Dokl. 
Akad. Nauk USSR, 176, 332 (1967)), UFT (Fujii, S., et al., Gann, 69, 763 
(1978)), Carmofur (Hoshi, A., et al., Gann, 67, 725 (1976)), Doxyfluridine 
(Cook, A. F., et al., J. Med. Chem., 22, 1330 (1979)), Cytarabine (Evance, 
J. S., et al., Proc. Soc. Exp. Bio. Med., 106, 350 (1961)), Ancytabine 
(Hoshi, A., et al., Gann, 63, 353, (1972)), Enocytabine (Aoshima, M., et 
al., Cancer Res., 36, 2726 (1976)), etc. are so far known. 
As the pyrimidine mononucleoside having a cyano group at the ribose moiety, 
3'-cyanothymine nucleoside and 3'-cyanouracil nucleoside derivatives are 
only known (Japanese Unexamined Patent Publication Nos. Hei-2-83392, 
Hei-2-104586 and Hei-2-503002). 
DISCLOSURE OF THE INVENTION 
The present inventors made extensive studies for a long period of time with 
a view to developing an absolutely novel antimetabolites which is superior 
to the existing antitumor agents described above to find that compounds 
wherein a cyano group is introduced to the 2'-position of the sugar moiety 
of pyrimidine series nucleosides have strong antitumor activities to 
various tumor systems and such compounds can be intermediates for 
producing such compounds having strong antitumor activities, and they 
accomplished the present invention. 
CONSTITUTION OF THE INVENTION 
The novel pyrimidine nucleoside derivatives having strong antitumor 
activities according to the present invention are compounds having the 
general formula: 
##STR2## 
or the general formula: 
##STR3## 
and pharmacologically acceptable nontoxic salts thereof. 
In the above general formulae (1) and (2), R.sup.1 represents a hydroxyl 
group or an amino group which may optionally have a substituent selected 
from the following group A or B; R.sup.2 represents a hydrogen atom or an 
alkyl group having 1 to 4 carbon atoms: R.sup.3 represents a hydrogen atom 
or a hydroxyl group; and R.sup.4 and R.sup.5 each represent a hydrogen 
atom or together may form a group --R.sup.6 R.sup.7 Si--O--SiR.sup.6' 
R.sup.7' -- (wherein R.sup.6, R.sup.7, R.sup.6' and R.sup.7' may be the 
same or different from one another and each represent an alkyl group 
having 1 to 4 carbon atoms). 
[Group A] 
Aliphatic acyl having 1 to 4 carbon atoms and aromatic acyl having 7 to 11 
carbon atoms which may have a substituent on the ring. 
[Group B] 
Alkoxycarbonyl having a C.sub.1 -C.sub.4 alkyl, alkenyloxycarbonyl having a 
C.sub.2 -C.sub.4 alkenyl, aralkyloxycarbonyl having 8 to 12 carbon atoms 
which may have a substituent on the ring. 
The aliphatic acyl having 1 to 4 carbon atoms as the substituent R.sup.1 
mentioned above includes formyl, acetyl, propionyl, butyryl and 
isopropionyl, preferably an aliphatic acyl having 1 to 2 carbon atoms. The 
aromatic acyl having 7 to 11 carbon atoms includes benzoyl, 
.alpha.-naphthoyl and .beta.-naphthoyl, preferably benzoyl. The 
substituent moiety on the aromatic ring includes an alkyl having 1 to 4 
carbon atoms, an alkoxy having 1 to 4 carbon atoms and an aliphatic acyl 
having 1 to 4 carbon atoms, preferably methyl, ethyl, methoxy, ethoxy and 
acetyl groups. The alkyl moiety of the alkoxycarbonyl having a C.sub.1 
-C.sub.4 alkyl group includes methyl, ethyl, n-propyl, isopropyl, n-butyl, 
isobutyl and t-butyl, preferably methyl and t-butyl. The alkenyl moiety of 
the alkenyloxycarbonyl having a C.sub.2 -C.sub.4 alkenyl includes vinyl, 
allyl, isopropenyl, 1-butenyl and 2-butenyl, preferably allyl. The aralkyl 
moiety of the aralkyloxycarbonyl having 8 to 12 carbon atoms includes 
benzyl, phenethyl, .alpha.-naphthylmethyl and .beta.-naphthylethyl, 
preferably benzyl. The substituent on the aromatic ring includes an alkyl 
having 1 to 4 carbon atoms, an alkoxy having 1 to 4 carbon atoms and an 
aliphatic acyloxy having 1 to 4 carbon atoms, preferably methyl, ethyl, 
methoxy, ethoxy and acetoxy. 
R.sup.1 mentioned above preferably includes a hydroxyl group, an amino 
group, an amino group substituted with a C.sub.1 -C.sub.2 aliphatic acyl, 
an amino group substituted with an aromatic acyl having 7 carbon atoms 
which may have a substituent on the ring, an amino group substituted with 
an alkoxycarbonyl having a C.sub.1 -C.sub.4 alkyl, an amino group 
substituted with an alkenyloxycarbonyl having a C.sub.3 alkenyl, an amino 
group substituted with an aralkyloxycarbonyl having 8 carbon atoms which 
may have a substituent on the ring, more preferably a hydroxyl group, an 
amino group, an amino group substituted with an aliphatic acyl having 1 to 
2 carbon atoms, an amino group substituted with an aromatic acyl having 7 
carbon atoms, most preferably a hydroxyl group and an amino group. 
The R.sup.2 alkyl group having 1 to 4 carbon atoms includes methyl, ethyl, 
propyl, isopropyl, butyl, isobutyl and t-butyl groups, preferably a methyl 
group. 
R.sup.2 mentioned above preferably includes a hydrogen atom and a methyl 
group. 
The R.sup.6, R.sup.6', R.sup.7 or R.sup.7' alkyl group having 1 to 4 carbon 
atoms includes methyl, ethyl, propyl, isopropyl, buryl, isobutyl and 
t-butyl groups, preferably isopropyl group. 
R.sup.4 and R.sup.5 mentioned above each are a hydrogen atom or together 
form a tetramethyldisiloxdiyl group, a tetraethyldisiloxdiyl group, a 
tetrapropyldisiloxdiyl group, a tetraisopropyldisiloxdiyl group, a 
tetrabutyldisiloxdiyl group, a diethyldiisopropyldisiloxdiyl group or a 
dibutyldiisopropyldisiloxdiyl group, preferably a hydrogen atom or a 
tetraisopropyldisiloxdiyl group, more preferably a hydrogen atom. 
The pharmacologically acceptable nontoxic salts of the compounds having the 
above general formulae (1) or (2) of the present invention can be 
exemplified by salts of mineral acids such as hydrochloride, hydrobromide 
and sulfate, organic sulfonates such as methane sulfonate and benzene 
sulfonate, aliphatic carboxylates such as acetate, propionate, butyrate, 
and caproate and aromatic carboxylates such as benzoate. 
Among those salts, the salts of mineral acids (particularly hydrochloric 
acid) and aliphatic carboxylates (particularly acetic acid) are preferred. 
In Compounds (1) and (2), there may preferably be mentioned: 
1) Compounds wherein R.sup.1 represents a hydroxyl group or an amino group 
which may have a substituent selected from the following group A' or B'; 
R.sup.2 represents a hydrogen atom or an alkyl group having 1 to 4 carbon 
atoms; R.sup.3 represents a hydrogen atom or a hydroxyl group; and R.sup.4 
and R.sup.5 each represent a hydrogen atom or together form a 
tetraisopropyldisiloxdiyl group. 
[Group A'] 
An aliphatic acyl having 1 to 2 carbon atoms and an aromatic acyl having 7 
carbon atoms which may have a substituent on the ring. 
[Group B'] 
An alkoxycarbonyl having a C.sub.1 -C.sub.4 alkyl, an alkenyloxycarbonyl 
having a C.sub.3 alkenyl and an aralkyloxycarbonyl having 8 carbon atoms 
which may have a substituent on the ring. 
2) Compounds wherein R.sup.1 represents a hydroxyl group or an amino group 
which may have a substituent selected from the following group A'; R.sup.2 
represents a hydrogen atom or a methyl group; R.sup.3 represents a 
hydrogen atom or a hydroxyl group; and R.sup.4 and R.sup.5 each represent 
a hydrogen atom. 
[Group A'] 
An aliphatic acyl having 1 to 2 carbon atoms and an aromatic acyl having 7 
carbon atoms which may have a substituent on the ring. 
3) Compounds wherein R.sup.1 represents a hydroxyl group or an amino group; 
R.sup.2 represents a hydrogen atom or a methyl group; R.sup.3 represents a 
hydrogen atom or a hydroxyl group; and R.sup.4 and R.sup.5 each represent 
a hydrogen atom. 
Compounds (1) and (2) of the present invention can typically be exemplified 
by those listed in Table 1, Table 2 and Table 3, but the present invention 
is not limited thereto. 
Incidentally, Table 1, Table 2 and Table 3 show compounds of the formula A, 
compounds of the formula B and compounds of the formula C, respectively. 
In Table 1, Table 2 and Table 3, Et, Pr, tBu, AL, Ac, Bz, BzpMe, BzpOMe, 
By and BypOAc mean an ethyl group, propyl group, tert-butyl group, allyl 
group, acetyl group, benzoyl group, p-methylbenzoyl group, 
p-methoxybenzoyl group, benzyl group and p-acetoxybenzyl group, 
respectively. 
##STR4## 
TABLE 1 
______________________________________ 
No. R.sup.1 R.sup.2 R.sup.7 
R.sup.8 
X 
______________________________________ 
1-1 NH.sub.2 H H CN -- 
1-2 NH.sub.2 CH.sub.3 H CN -- 
1-3 NH.sub.2 CH.sub.3 CH.sub.2 
H CN -- 
1-4 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
1-5 NH.sub.2 (CH.sub.3).sub.2 CH 
H CN -- 
1-6 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
1-7 NH.sub.2 H H CN HCl 
1-8 NH.sub.2 CH.sub.3 H CN HCl 
1-9 NH.sub.2 CH.sub.3 CH.sub.2 
H CN HCl 
1-10 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
H CN HCl 
1-11 NH.sub.2 (CH.sub.3).sub.2 CH 
H CN HCl 
1-12 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
H CN HCl 
1-13 OH H H CN -- 
1-14 OH CH.sub.3 H CN -- 
1-15 OH CH.sub.3 CH.sub.2 
H CN -- 
1-16 OH CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
1-17 OH (CH.sub.3).sub.2 CH 
H CN -- 
1-18 OH CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
1-19 NH.sub.2 H CN OH -- 
1-20 NH.sub.2 CH.sub.3 CN OH -- 
1-21 NH.sub.2 CH.sub.3 CH.sub.2 
CN OH -- 
1-22 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
CN OH -- 
1-23 NH.sub.2 (CH.sub.3).sub.2 CH 
CN OH -- 
1-24 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
CN OH -- 
1-25 NH.sub.2 H CN OH HCl 
1-26 NH.sub.2 CH.sub.3 CN OH HCl 
1-27 NH.sub.2 CH.sub.3 CH.sub.2 
CN OH HCl 
1-28 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
CN OH HCl 
1-29 NH.sub.2 (CH.sub.3).sub.2 CH 
CN OH HCl 
1-30 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
CN OH HCl 
1-31 OH H CN OH -- 
1-32 OH CH.sub.3 CN OH -- 
1-33 OH CH.sub.3 CH.sub.2 
CN OH -- 
1-34 OH CH.sub.3 (CH.sub.2).sub.2 
CN OH -- 
1-35 OH (CH.sub.3).sub.2 CH 
CN OH -- 
1-36 OH CH.sub.3 (CH.sub.2).sub.3 
CN OH -- 
1-37 NH.sub.2 H CN H -- 
1-38 NH.sub.2 CH.sub.3 CN H -- 
1-39 NH.sub.2 CH.sub.3 CH.sub.2 
CN H -- 
1-40 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
1-41 NH.sub.2 (CH.sub.3).sub.2 CH 
CN H -- 
1-42 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
1-43 NH.sub.2 H CN H HCl 
1-44 NH.sub.2 CH.sub.3 CN H HCl 
1-45 NH.sub.2 CH.sub.3 CH.sub.2 
CN H HCl 
1-46 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
CN H HCl 
1-47 NH.sub.2 (CH.sub.3).sub.2 CH 
CN H HCl 
1-48 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
CN H HCl 
1-49 OH H CN H -- 
1-50 OH CH.sub.3 CN H -- 
1-51 OH CH.sub.3 CH.sub.2 
CN H -- 
1-52 OH CH.sub.3 (CH.sub.2 ).sub.2 
CN H -- 
1-53 OH (CH.sub.3).sub.2 CH 
CN H -- 
1-54 OH CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
1-55 NH.sub.2 H OH CN -- 
1-56 NH.sub.2 CH.sub.3 OH CN -- 
1-57 NH.sub.2 CH.sub.3 CH.sub.2 
OH CN -- 
1-58 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
1-59 NH.sub.2 (CH.sub.3).sub.2 CH 
OH CN -- 
1-60 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
1-61 NH.sub.2 H OH CN HCl 
1-62 NH.sub.2 CH.sub.3 OH CN HCl 
1-63 NH.sub.2 CH.sub.3 CH.sub.2 
OH CN HCl 
1-64 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
OH CN HCl 
1-65 NH.sub.2 (CH.sub.3).sub.2 CH 
OH CN HCl 
1-66 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
OH CN HCl 
1-67 OH H OH CN -- 
1-68 OH CH.sub.3 OH CN -- 
1-69 OH CH.sub.3 CH.sub.2 
OH CN -- 
1-70 OH CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
1-71 OH (CH.sub.3).sub.2 CH 
OH CN -- 
1-72 OH CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
1-73 NHBz H H CN -- 
1-74 NHCOOtBu H H CN -- 
1-75 NHCOOBy H H CN -- 
1-76 NHCOOAL H H CN -- 
1-77 NHBz CH.sub.3 H CN -- 
1-78 NHBz CH.sub.3 CH.sub.2 
H CN -- 
1-79 NHBz CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
1-80 NHBz (CH.sub.3).sub.2 CH 
H CN -- 
1-81 NHBz CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
1-82 NHBz H CN H -- 
1-83 NHBz CH.sub.3 CN H -- 
1-84 NHBz CH.sub.3 CH.sub.2 
CN H -- 
1-85 NHBz CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
1-86 NHBz (CH.sub.3).sub.2 CH 
CN H -- 
1-87 NHBz CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
1-88 NHAc H H CN -- 
1-89 NHCOH H H CN -- 
1-90 NHCOEt H H CN -- 
1-91 NHCOPr H H CN -- 
1-92 NHAc CH.sub.3 H CN -- 
1-93 NHAc CH.sub.3 CH.sub.2 
H CN -- 
1-94 NHAc CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
1-95 NHAc (CH.sub.3).sub.2 CH 
H CN -- 
1-96 NHAc CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
1-97 NHAc H OH CN -- 
1-98 NHAc CH.sub.3 OH CN -- 
1-99 NHAc CH.sub.3 CH.sub.2 
OH CN -- 
1-100 
NHAc CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
1-101 
NHAc (CH.sub.3).sub.2 CH 
OH CN -- 
1-102 
NHAc CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
1-103 
NHAc H CN H -- 
1-104 
NHAc CH.sub.3 CN H -- 
1-105 
NHAc CH.sub.3 CH.sub.2 
CN H -- 
1-106 
NHAc CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
1-107 
NHAc (CH.sub.3).sub.2 CH 
CN H -- 
1-108 
NHAc CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
______________________________________ 
TABLE 2 
______________________________________ 
No. R.sup.1 R.sup.2 X 
______________________________________ 
2-1 NH.sub.2 H -- 
2-2 NH.sub.2 CH.sub.3 -- 
2-3 NH.sub.2 CH.sub.3 CH.sub.2 
-- 
2-4 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
-- 
2-5 NH.sub.2 (CH.sub.3).sub.2 CH 
-- 
2-6 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
-- 
2-7 NH.sub.2 H HCl 
2-8 NH.sub.2 CH.sub.3 HCl 
2-9 NH.sub.2 CH.sub.3 CH.sub.2 
HCl 
2-10 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
HCl 
2-11 NH.sub.2 (CH.sub.3).sub.2 CH 
HCl 
2-12 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
HCl 
2-13 OH H -- 
2-14 OH CH.sub.3 -- 
2-15 OH CH.sub.3 CH.sub.2 
-- 
2-16 OH CH.sub.3 (CH.sub.2).sub.2 
-- 
2-17 OH (CH.sub.3).sub.2 CH 
-- 
2-18 OH CH.sub.3 (CH.sub.2).sub.3 
-- 
2-19 NHAc H -- 
2-20 NHAc CH.sub.3 -- 
2-21 NHAc CH.sub.3 CH.sub.2 
-- 
2-22 NHAc CH.sub.3 (CH.sub.2).sub.2 
-- 
2-23 NHAc (CH.sub.3).sub.2 CH 
-- 
2-24 NHAc CH.sub.3 (CH.sub.2).sub.3 
-- 
2-25 NHBzpMe H -- 
2-26 NHBzpOMe CH.sub.3 -- 
2-27 NHCOOtBu CH.sub.3 CH.sub.2 
-- 
2-28 NHCOOBy CH.sub.3 (CH.sub.2).sub.2 
-- 
2-29 NHCOOAL (CH.sub.3).sub.2 CH 
-- 
2-30 NHCOOBypOAc CH.sub.3 (CH.sub.2).sub.3 
-- 
2-31 NHBz H -- 
2-32 NHBz CH.sub.3 -- 
2-33 NHBz CH.sub.3 CH.sub.2 
-- 
2-34 NHBz CH.sub.3 (CH.sub.2).sub.2 
-- 
2-35 NHBz (CH.sub.3).sub.2 CH 
-- 
2-36 NHBz CH.sub.3 (CH.sub.2).sub.3 
-- 
2-37 NHAc H -- 
2-38 NHAc CH.sub.3 -- 
2-39 NHAc CH.sub.3 CH.sub.2 
-- 
2-40 NHAc CH.sub.3 (CH.sub.2).sub.2 
-- 
2-41 NHAc (CH.sub.3).sub.2 CH 
-- 
2-42 NHAc CH.sub.3 (CH.sub.2).sub.3 
-- 
______________________________________ 
TABLE 3 
______________________________________ 
No. R.sup.1 R.sup.2 R.sup.7 
R.sup.8 
X 
______________________________________ 
3-1 NH.sub.2 H H CN -- 
3-2 NH.sub.2 CH.sub.3 H CN -- 
3-3 NH.sub.2 CH.sub.3 CH.sub.2 
H CN -- 
3-4 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
3-5 NH.sub.2 (CH.sub.3).sub.2 CH 
H CN -- 
3-6 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
3-7 OH H H CN -- 
3-8 OH CH.sub.3 H CN -- 
3-9 OH CH.sub.3 CH.sub.2 
H CN -- 
3-10 OH CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
3-11 OH (CH.sub.3).sub.2 CH 
H CN -- 
3-12 OH CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
3-13 NH.sub.2 H CN OH -- 
3-14 NH.sub.2 CH.sub.3 CN OH -- 
3-15 NH.sub.2 CH.sub.3 CH.sub.2 
CN OH -- 
3-16 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
CN OH -- 
3-17 NH.sub.2 (CH.sub.3).sub.2 CH 
CN OH -- 
3-18 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
CN OH -- 
3-19 OH H CN OH -- 
3-20 OH CH.sub.3 CN OH -- 
3-21 OH CH.sub.3 CH.sub.2 
CN OH -- 
3-22 OH CH.sub.3 (CH.sub.2).sub.2 
CN OH -- 
3-23 OH (CH.sub.3).sub.2 CH 
CN OH -- 
3-24 OH CH.sub.3 (CH.sub.2).sub.3 
CN OH -- 
3-25 NH.sub.2 H CN H -- 
3-26 NH.sub.2 CH.sub.3 CN H -- 
3-27 NH.sub.2 CH.sub.3 CH.sub.2 
CN H -- 
3-28 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
3-29 NH.sub.2 (CH.sub.3).sub.2 CH 
CN H -- 
3-30 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
3-31 OH H CN H -- 
3-32 OH CH.sub.3 CN H -- 
3-33 OH CH.sub.3 CH.sub.2 
CN H -- 
3-34 OH CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
3-35 OH (CH.sub.3).sub.2 CH 
CN H -- 
3-36 OH CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
3-37 NH.sub.2 H OH CN -- 
3-38 NH.sub.2 CH.sub.3 OH CN -- 
3-39 NH.sub.2 CH.sub.3 CH.sub.2 
OH CN -- 
3-40 NH.sub.2 CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
3-41 NH.sub.2 (CH.sub.3).sub.2 CH 
OH CN -- 
3-42 NH.sub.2 CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
3-43 OH H OH CN -- 
3-44 OH CH.sub.3 OH CN -- 
3-45 OH CH.sub.3 CH.sub.2 
OH CN -- 
3-46 OH CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
3-47 OH (CH.sub.3).sub.2 CH 
OH CN -- 
3-48 OH CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
3-49 NHAc H H CN -- 
3-50 NHAc CH.sub.3 H CN -- 
3-51 NHAc CH.sub.3 CH.sub.2 
H CN -- 
3-52 NHAc CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
3-53 NHAc (CH.sub.3).sub.2 CH 
H CN -- 
3-54 NHAc CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
3-55 NHAc H CN OH -- 
3-56 NHAc CH.sub.3 CN OH -- 
3-57 NHAc CH.sub.3 CH.sub.2 
CN OH -- 
3-58 NHAc CH.sub.3 (CH.sub.2).sub.2 
CN OH -- 
3-59 NHAc (CH.sub.3).sub.2 CH 
CN OH -- 
3-60 NHAc CH.sub.3 (CH.sub.2).sub.3 
CN OH -- 
3-61 NHAc H CN H -- 
3-62 NHAc CH.sub.3 CN H -- 
3-63 NHAc CH.sub.3 CH.sub.2 
CN H -- 
3-64 NHAc CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
3-65 NHAc (CH.sub.3).sub.2 CH 
CN H -- 
3-66 NHAc CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
3-67 NHAc H OH CN -- 
3-68 NHAc CH.sub.3 OH CN -- 
3-69 NHAc CH.sub.3 CH.sub.2 
OH CN -- 
3-70 NHAc CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
3-71 NHAc (CH.sub.3).sub.2 CH 
OH CN -- 
3-72 NHAc CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
3-73 NHBz H H CN -- 
3-74 NHBz CH.sub.3 H CN -- 
3-75 NHBz CH.sub.3 CH.sub.2 
H CN -- 
3-76 NHBz CH.sub.3 (CH.sub.2).sub.2 
H CN -- 
3-77 NHBz (CH.sub.3).sub.2 CH 
H CN -- 
3-78 NHBz CH.sub.3 (CH.sub.2).sub.3 
H CN -- 
3-79 NHBz H CN OH -- 
3-80 NHBz CH.sub.3 CN OH -- 
3-81 NHBz CH.sub.3 CH.sub.2 
CN OH -- 
3-82 NHBz CH.sub.3 (CH.sub.2).sub.2 
CN OH -- 
3-83 NHBz (CH.sub.3).sub.2 CH 
CN OH -- 
3-84 NHBz CH.sub.3 (CH.sub.2).sub.3 
CN OH -- 
3-85 NHBz H CN H -- 
3-86 NHBz CH.sub.3 CN H -- 
3-87 NHBz CH.sub.3 CH.sub.2 
CN H -- 
3-88 NHBz CH.sub.3 (CH.sub.2).sub.2 
CN H -- 
3-89 NHBz (CH.sub.3).sub.2 CH 
CN H -- 
3-90 NHBz CH.sub.3 (CH.sub.2).sub.3 
CN H -- 
3-91 NHBz H OH CN -- 
3-92 NHBz CH.sub.3 OH CN -- 
3-93 NHBz CH.sub.3 CH.sub.2 
OH CN -- 
3-94 NHBz CH.sub.3 (CH.sub.2).sub.2 
OH CN -- 
3-95 NHBz (CH.sub.3).sub.2 CH 
OH CN -- 
3-96 NHBz CH.sub.3 (CH.sub.2).sub.3 
OH CN -- 
______________________________________ 
Among the above exemplary compounds, preferred are: 
1-1, 1-2, 1-7, 1-8, 1-13, 1-14, 1-19, 1-20, 1-25, 1-26, 1-31, 1-32, 1-37, 
1-38, 1-43, 1-44, 1-49, 1-50, 1-55, 1-56, 1-61, 1-62, 1-67, 1-68, 1-73, 
1-77, 1-82, 1-83, 1-88, 1-89, 1-92, 1-97, 1-98, 1-103, 1-104, 2-1, 2-2, 
2-7, 2-8, 2-13, 2-14, 2-19, 2-20, 2-25, 2-26, 2-31, 2-32, 2-37, 2-38, 3-1, 
3-2, 3-7, 3-8, 3-13, 3-14, 3-19, 3-20, 3-25, 3-26, 3-31, 3-32, 3-37, 3-38, 
3-43, 3-44, 3-49, 3-50, 3-55, 3-56, 3-61, 3-62, 3-67, 3-68, 3-73, 3-74, 
3-79, 3-80, 3-85, 3-86, 3-91 and 3-92. 
Among the above exemplary compounds, more preferred are: 
1-1, 1-2, 1-7, 1-8, 1-13, 1-14, 1-19, 1-20, 1-25, 1-26, 1-31, 1-32, 1-37, 
1-38, 1-43, 1-44, 1-49, 1-50, 1-55, 1-56, 1-61, 1-62, 1-67, 1-68, 1-73, 
1-77, 1-82, 1-83, 1-88, 1-89, 1-92, 1-97, 1-98, 1-103, 1-104, 2-1, 2-2, 
2-7, 2-8, 2-13, 2-14, 2-19, 2-20, 2-25, 2-26, 2-31, 2-32, 2-37 and 2-38. 
Among the above exemplary compounds, still more preferred are: 
1-1, 1-2, 1-7, 1-8, 1-13, 1-14, 1-19, 1-20, 1-25, 1-26, 1-31, 1-32, 1-37, 
1-38, 1-43, 1-44, 1-49, 1-50, 1-55, 1-56, 1-61, 1-62, 1-67, 1-68, 2-1, 
2-2, 2-7, 2-8, 2-13 and 2-14. 
Among the above exemplary compounds, most preferred are: 
1, 1-7, 1-13, 1-14, 1-19, 1-25, 1-31, 1-32, 1-37, 1-43, 1-49, 1-50, 1-55, 
1-61, 1-67, 1-68, 2-1, 2-7, 2-13 and 2-14. 
##STR5## 
Compounds (1) and (2) of the present invention can be prepared using uracil 
or a 5-lower alkyluracil, a known compound (3), [M. Muraoka, A. Tanaka and 
T. Ueda, Chem. Pharm. Bull., 18, 261 (1970)] following the reaction steps 
shown in Reaction Schemes 1, 2, 3 and 4. In Schemes 1, 2, 3 and 4, R.sup.1 
and R.sup.2 have the same meanings as defined above, R.sup.4a and R.sup.5a 
together represent a group of the formula: --R.sup.6 R.sup.7 
Si--O--SiR.sup.6' R.sup.7' -- (wherein R.sup.6, R.sup.7, R.sup.6' and 
R.sup.7' have the same meanings as defined above). R.sup.9 represents an 
alkoxythiocarbonyl group having a C.sub.1 -C.sub.4 alkyl or an 
aryloxythiocarbonyl group having a C.sub.6 -C.sub.10 aryl. The alkyl 
having 1 to 4 carbon atoms includes methyl, ethyl propyl, butyl, etc., and 
the aryl having 6 to 10 carbon atoms includes pheny, naphthyl, etc., 
preferably methyl and phenyl, respectively. R.sup.10 represents a 
triarylmethyl group wherein the aryl moiety may be substituted, whereas 
the aryl moiety includes phenyl, naphthyl, etc., preferably phenyl. The 
substituent for the aryl moiety includes an alkyl group having 1 to 4 
carbon atoms such as methyl, ethyl, propyl and buryl, an alkoxy group 
having 1 to 4 carbon atoms such as methoxy, ethoxy, propoxy and butoxy, 
and an acyloxy group having 2 to 4 carbon atoms such as acetoxy, propyloxy 
and butyryloxy, preferably methyl and methoxy group. X represents a 
halogen atom, preferably chlorine or bromine. The respective reaction 
steps will be explained below in detail. 
(Step 1) 
This step is for preparing Compound (4) by ribosylating Compound (3). 
Ribosylation is generally carried out by methods customarily employed in 
the art, for example, as follows: 
(i) A mercury salt of compound (3) to be obtained by addition of an 
alcoholic solution of mercuric chloride to an aqueous sodium hydroxide 
solution of compound (3) is reacted with a known compound 
2',3',5'-tri-O-benzoyl-D-ribosyl chloride in benzene. Sodium methoxide is 
allowed to act on the resulting compound in methanol to obtain Compound 
(4) [M. Muraoka, A. Tanaka and T. Ueda, Chem. Pharm. Bull., 18, 261 
(1970)] and 
(ii) Compound (3) is reacted with trimethylsilyl chloride in benzene in the 
presence of an organic amine such as triethylamine to obtain 
bis(trimethylsilyl)uracil, which is reacted with 
2',3',5'-tri-O-benzoyl-D-ribosyl chloride, followed by reaction of the 
resulting compound with sodium methoxide in methanol to obtain Compound 
(4) [T. Nishimura, B. Shimizu and I. Iwai, Chem. Pharm. Bull., 11, 1470 
(1963)]. 
(Step 2) 
This step is for preparing Compound (5) by converting the carbonyl moiety 
at the 4-position of Compound (4) to an amino group. 
The conversion to an amino group is generally carried out by methods 
customarily employed in the art, for example, as follows: 
(i) Hexamethyldisilazane and ammonium sulfate are allowed to act on 
Compound (4) with heating in anhydrous formamide to obtain Compound (5) 
[Compiled by Townsend and Tipson, Nucleic Acid Chemistry, 227 (1978)] 
(ii) The hydroxyl groups at the 2'-, 3'- and 5'-positions of Compound (4) 
are protected by acetylation or benzoylation. In chloroform containing no 
alcohol, thionyl chloride and anhydrous dimethylformamide are acted on the 
resulting compound, followed by treatment with a methanol solution of 
ammonia to obtain Compound (5) [Compiled by Townsend and Tipson, Nucleic 
Acid Chemistry, 223 (1978)] 
(iii) The hydroxyl groups at the 2'-, 3'- and 5'-positions of Compound (4) 
are protected by acetylation or benzoylation, and diphosphorus 
pentasulfide is acted thereon in pyridine to obtain a 4-thio compound. A 
lower alkyl iodide such as methyl iodide and ethyl iodide and an alkali 
metal hydroxide such as sodium hydroxide is acted on the resulting 
compound to obtain a 4-alkylthio compound as an intermediate compound. The 
4-alkylthio compound is further treated with a liquid ammonia to obtain 
Compound (5) [J. J. Fox, N. Miller and I. Wenpen, Journal of Medicinal 
Chemistry, 9, 101 (1966)]. 
(Step 3) 
In this step, X--R.sup.6 R.sup.7 Si--O--SiR.sup.6 'R.sup.7 '--X is acted on 
the 3'- and 5'-positions of Compound (4) and these positions are protected 
at the same time to obtain Compound (5). This step is carried out by the 
known method [M. J. Robins, J. S. Wilson, L. Sawyer and M. N. G. James, 
Can. J. Chem., 61, 1911, (1983)]. 
As the solvent employable, there may preferably be mentioned a basic 
solvent such as pyridine. 
Reaction is carried out at a temperature of -10.degree. to 100.degree. C., 
preferably 0.degree. to 50.degree. C. 
While the reaction time varies depending on the compound and reaction 
temperature employed, it is usually from 1 hour to 30 hours, preferably 1 
hour to 5 hours. 
After completion of the reaction, for example, the solvent is distilled 
off, and the reaction mixture is poured in water. The resulting mixture is 
extracted with a water-immiscible solvent such as benzene, ether and ethyl 
acetate and the solvent is distilled off from the extract to obtain a 
compound. The thus obtained compound is used as such in the subsequent 
step. If desired, the compound can be purified by isolation by means of 
various chromatographic procedures or recrystallization. 
(Step 3') 
This step is for acylating the amino group at the 4-position of Compound 
(5) and for acting X--R.sup.6 R.sup.7 Si--O--SiR.sup.6 'R.sup.7 '--X on 
the thus acylated compound to protect the 3'- and 5'-positions at the same 
time whereby to obtain Compound (6). The 3'- and 5'-positions can be 
protected in the same manner as in Step 3. 
The acylation of the amino group at the 4-position is carried out by the 
method generally employed in the art. For example, in the case of an 
aliphatic acyl or aromatic acyl, the reactive derivative of the 
corresponding carboxylic acid such as an acid halide or an acid anhydride 
is allowed to react or the corresponding carboxylic acid is allowed to 
react in the presence of a condensing agent: or in the case of 
alkoxycarbonyl, alkenyloxycarbonyl or aralkyloxycarbonyl, a halogenoformic 
acid ester having the corresponding alkoxy, alkenyloxy or aralkyloxy 
group, or dialkyl dicarbonate, dialkenyl dicarbonate or diaralkyl 
dicarbonate having the corresponding alkyl, alkenyl or aralkyl group is 
allowed to react. 
As the acid halide employable, there may be mentioned, for example, acid 
chlorides and acid bromides. 
As the condensing agent employable, there may be mentioned, for example, 
N,N'-dicyclohexylcarbodiimide (DCC), 1,1'-oxalyldiimiaazole, 
2,2'-dipyridyldisulfide, N,N'-disuccinimidyl carbonate, 
N,N'-bis(2-oxo-3-oxazolydinyl)-phosphinic chloride, N,N'-carbodiimidazole, 
N,N'-disuccinimidyl oxalate (DSO), N,N'-diphthalimide oxalate (DPO), 
N,N'-bis(norbornenylsuccinimidyl)oxalate (BNO), 
1,1'-bis(benzotriazolyl)oxalate (BBTO), 
1,1'-bis(6-chlorobenzotriazolyl)oxalate (BCTO), 
1,1'-bis(6-trifluoromethylbenzotriazolyl)oxalate (BTBO), etc. 
The solvent employable is not particularly limited unless it inhibits the 
reaction and includes aromatic hydrocarbons such as benzene, toluene and 
xylene, ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, 
dioxane, dimethoxyethane and diethylene glycol diemethyl ether, alcohols 
such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, 
t-butanol, isoamyl alcohol, diethylene glycol, glycerol, octanol, 
cyclohexanol and methyl cellosolve, ketones such as acetone, methyl ethyl 
ketone, methyl isobutyl ketone, isophorone and cyclohexanone, nitriles 
such as acetonitrile and isobutyronitrile, amides such as formamide, 
dimethylformamide, dimethylacetamide and hexamethylphosphorotriamide, 
sulfoxides such as dimethyl sulfoxide and sulfolane, and mixed solvents of 
these organic solvents and water, preferably aromatic hydrocarbons such as 
benzene, toluene and xylene, ethers such as diethyl ether, diisopropyl 
ether, tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol 
dimethyl ether, alcohols such as-methanol, ethanol, n-propanol, 
isopropanol, n-butanol, isobutanol, t-butanol, isoamyl alcohol, diethylene 
glycol, glycerol, octanol, cyclohexanol and methyl cellosolve, ketones 
such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone 
and cyclohexanone, nitriles such as acetonitrile and isobutyronitrile, 
amides such as formamide, dimethylformamide, dimethylacetamide and 
hexamethylphosphorotriamide, sulfoxides such as dimethyl sulfoxide and 
sulfolane, and mixed solvents of these organic solvents and water. 
Reaction is carried out at a temperature of 0.degree. C. to 150.degree. C., 
preferably 0.degree. C. to 100.degree. C. 
While reaction time varies depending on the compound, reaction temperature, 
etc. employed, it is usually from 1 hour to 30 hours, preferably 2 hours 
to 5 hours. 
After completion of the rection, for example, the solvent is distilled off, 
and the reaction mixture is poured in water. The resulting mixture is 
extracted with a water-immiscible solvent such as benzene, ether and ethyl 
acetate and the solvent is distilled off from the extract to obtain a 
compound. The thus obtained compound is usually used as such in the 
subsequent step. If desired, the compound can be purified by isolation by 
means of various chromatographic procedures or recrystallization. 
(Step 4) 
This step is for preparing Compound (7) by treating Compound (6) with a 
thiocarbonylating reagent in an inert solvent to effect thiocarbonylation 
by substitution of the hydroxyl group at the 2'-position of Compound (5). 
The solvent employable is not particularly limited unless it inhibits the 
reaction and includes amides such as dimethylformamide and 
dimethylacetamide, sulfoxides such as dimethyl sulfoxide and nitriles such 
as acetonitrile, preferably acetonitrile. 
While the reagent employable is not particularly limited, if it is a 
hydroxyl group thiocarbonylating reagent, and it includes lower 
alkoxycarbonyl halides such as methoxythiocarbonyl chloride and 
ethoxythiocarbonyl chloride, and arylthiocarbonyl halides such as 
phenoxythiocarbonyl chloride and naphthoxythiocarbonyl chloride. 
Reaction is carried out at a temperature of -20.degree. C. to 50.degree. 
C., preferably -10.degree. C. to 10.degree. C. 
While reaction time varies depending on the compound, reaction temperature, 
etc. employed, it is usually from 1 hour to 30 hours, preferably 2 hours 
to 5 hours. 
In order to carry out efficiently the reaction, organic amines such as 
4,4-dimethylaminopyridine and triethylamine can be used. 
After completion of the reaction, the desired compound can be obtained by 
the conventional method. For example, the reaction mixture is poured in 
water, the resulting mixture is extracted with a water-immiscible solvent 
such as benzene, ether and ethyl acetate and the solvent is distilled off 
from the extract to obtain the desired compound. The thus obtained 
compound is usually used as such in the subsequent step. If desired, the 
compound can be purified by isolation by means of various chromatographic 
procedures or recrystallization. 
(Step 5) 
This step is for preparing Compound (1a), which is the desired compound (1) 
wherein R.sup.4 and R.sup.5 together represent a group of the formula: 
--R.sup.6 R.sup.7 Si-O-SiR.sup.6 'R.sup.7 '--; and R.sup.3 represents a 
hydrogen atom by treating Compound (7) obtained in Step 4 with a reducing 
agent and a nitrilizing reagent in an inert solvent. 
The solvent employable is not particularly limited unless it inhibits the 
reaction and includes aliphatic hydrocarbons such as hexane, heptane, 
ligroin and petroleum ether, aromatic hydrocarbons such as benzene, 
toluene and xylene, ethers such as diethyl ether, diisopropyl ether, 
tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol diemethyl 
ether and aromatic hydrocarbons such as benzene, toluene and xylene, 
preferably aromatic hydrocarbons such as benzene and toluene. 
The nitrilizing reagent employable preferably includes alkylisonitriles 
such as t-butylisonitrile, while the reducing reagent employable 
preferably includes trialkyltin hydride having 1 to 4 carbon atoms such as 
tributyltin hydride. 
Reaction is carried out at a temperature of 50.degree. C. to 250.degree. 
C., preferably 80.degree. C. to 150.degree. C. While reaction time varies 
depending on the compound, reaction temperature, etc. employed, it is 
usually from 30 minutes to 12 hours, preferably 1 hour to 5 hours. 
In order to carry out efficiently the reaction, a radical initiator such as 
azoisobutyronitrile can be used as a catalyst. 
The Compound (1a) obtained immediately after the reaction in this step is a 
mixture of compounds wherein the coordination of the nitrile group is 
.alpha.- and .beta.-coordination, respectively. Such compounds can be 
subjected, for example, to adsorption or ion exchange chromatography using 
various carriers such as an activated carbon and silica gel, gel 
filtration using a Cephadex column, or recrystallization using an organic 
solvent such as ether, ethyl acetate and chloroform to separate the 
mixture into the respective compounds depending on the purpose. 
(Step 6) 
This step is for preparing Compound (8) by oxidizing the hydroxyl group at 
the 2'-position of Compound (6) and can be carried out using known 
methods. [F. Hansske et al., Tetrahedron 40, 125, (1984)]. 
The solvent employable is not particularly limited as long as it does not 
inhibit the reaction and can dissolve the starting materials therein to 
some degree. and it includes aromatic hydrocarbons such as benzene, 
toluene and xylene, halogenated hydrocarbons such as methylene chloride 
and chloroform, ethers such as ether, tetrahydrofuran, dioxane and 
dimethoxyethane, amides such as diemethylformamide, dimethylacetamide and 
hexamethylphosphorotriamide, sulfoxides such as dimethyl sulfoxide, 
ketones such as acetone and methyl ethyl ketone, and nitriles such as 
acetonitrile, preferably halogenated hydrocarbons such as methylene 
chloride and chloroform. 
Reaction is carried out at a temperature of0.degree. C. to 100.degree. C., 
preferably 10.degree. C. to 40.degree. C. 
While reaction time varies depending on the compound, reaction temperature, 
etc. employed, it is usually from 10 minutes to 12 hours, preferably 30 
minutes to 3 hours. 
Incidentally, the above oxidation reaction can be accelerated by adding an 
interlayer moving catalyst such as triethylbenzylammonium chloride and 
tributylbenzylammonium bromide. 
Reaction is carried out at a temperature of 0.degree. C. to 100.degree. C., 
preferably 10.degree. C. to 40.degree. C. 
While reaction time varies depending on the compound, reaction temperature, 
etc. employed, it is usually 10 minutes to 12 hours, preferably 30 minutes 
to 3 hours. 
Compound (8) obtained in this step can be collected, separated and purified 
by combining suitably various methods. For example, the reaction mixture 
is poured in water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene, ether and ethyl acetate, and the 
solvent is distilled off from the extract to obtain the Compound (8). If 
necessary, thus obtained compound can further be subjected, for example, 
to adsorption or ion exchange chromatography using various carriers such 
as an activated carbon and silica gel, gel filtration using a Cephadex 
column or recrystallization using an organic solvent such as ether, ethyl 
acetate and chloroform. 
(Step 7) 
This step is for preparing the desired Compound (1b) by acting a cyanide on 
Compound (8) in an inert solvent in the presence of a base. 
The solvent employable is not particularly limited unless it inhibits the 
reaction and includes a mixed solvent of an aliphatic hydrocarbon such as 
hexane, heptane, ligroin and petroleum ether with water, a mixed solvent 
of an aromatic hydrocarbon such as benzene, toluene and xylene with water, 
a mixed solvent of an ether such as diethyl ether, diisopropyl ether, 
tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol diemethyl 
ether with water, preferably a mixed solvent of an ether with water. 
The base employable is not particularly limited, and there may be mentioned 
organic bases and inorganic bases including alkali methal hydroxides such 
as sodium hydroxide and potassium hydroxide and alkali metal carbonates 
such as sodium carbonate and potassium carbonate, preferably alkali metal 
hydrogencarbonate. 
The cyanide employable is not particularly limited as long as it is soluble 
in water to form a cyano ion, and preferably includes cyanides of alkali 
metals such as sodium cyanide and potassium cyanide. 
Reaction is carried out at a temperature of 0.degree. C. to 100.degree. C., 
preferably 10.degree. C. to 40.degree. C. 
While reaction time varies depending on the compound, reaction temperature, 
etc. employed, it is usually 30 minutes to 96 hours, preferably 5 hours to 
24 hours. 
Compound (1b) obtained in this step can be collected, separated and 
purified by combining suitably various methods. For example, the reaction 
mixture is poured in water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene, ether and ethyl acetate, and the 
solvent is distilled off from the extract to obtain the desired compound. 
If necessary, thus obtained compound can further be subjected, for 
example, to adsorption or ion exchange chromatography using various 
carriers such as an activated carbon and silica gel, gel filtration using 
a Cephadex column or recrystallization using an organic solvent such as 
ether, ethyl acetate and chloroform. 
The compound (1b) obtained immediately after the reaction in this step is a 
mixture of compounds wherein the coordination of the nitrile group is 
.alpha.- and .beta.-configuration, respectively. Such compounds can be 
subjected, for example, to adsorption or ion exchange chromatography using 
various carriers such as an activated carbon and silica gel, gel 
filtration using a Cephadex column or recrystallization using an organic 
solvent such as ether, ethyl acetate and chloroform to separate the 
mixture into the respective compounds depending on the purpose. 
(Step 8) 
This step is for preparing Compound (9) by treating Compound (1b) with a 
thiocarbonylating reagent in an inert solvent to effect thiocarbonylation 
by substitution of the hydroxyl group at the 2'-position of Compound (1b) 
and can be carried out in the same manner as in Step 4. 
(Step 9) 
This step is for preparing Compound (1a) by reductively eliminating the 
thiocarbonyloxy group at the 2'-position of Compound (9). 
The solvent employable is not particularly limited unless it inhibits the 
reaction and includes aliphatic hydrocarbons such as hexane, heptane, 
ligroin and petroleum ether, aromatic hydrocarbons such as benzene, 
toluene and xylene, ethers such as diethyl ether. diisopropyl ether, 
tetrahydrofuran, dioxane, dimethoxyethane and diethylene glycol dimethyl 
ether and aromatic hydrocarbons such as benzene and toluene, preferably 
aromatic hydrocarbons such as benzene and toluene. 
The reagent employable includes preferably trialkyltin hydrides such as 
tributyltin hydride. 
Reaction is carried out usually at a temperature of 50.degree. C. to 
250.degree. C., preferably at the boiling point of the solvent employed. 
Reaction time is usually from 30 minutes to 10 hours, preferably 30 minutes 
to 3 hours. 
In order to carry out efficiently the reaction, a radical initiator such as 
azoisobutyronitrile can be used as a catalyst. 
The desired compound thus obtained can be collected, separated and purified 
by combining suitably various methods. For example, the reaction mixture 
is poured into water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene, ether and ethyl acetate, and the 
solvent is. distilled off from the extract to obtain the desired compound. 
If necessary, thus obtained compound can further be subjected, for 
example, to adsorption or ion exchange chromatography using various 
carriers such as an activated carbon and silica gel, gel filtration using 
a Cephadex column or recrystallization using an organic solvent such as 
ether, ethyl acetate and chloroform. 
The compound (1a) obtained immediately after the reaction in this step is a 
mixture of compounds wherein the coordination of the nitrile group is 
.alpha. and .beta.-configuration, respectively. Such compounds can be 
subjected, for example, to adsorption or ion exchange chromatography using 
various carriers such as an activated carbon and silica gel, gel 
filtration using a Cephadex column or recrystallization using an organic 
solvent such as ether, ethyl acetate and chloroform to separate the 
mixture into the respective compounds depending on the purpose. 
(Steps 10 and 12) 
These steps are for preparing the desired Compounds (1c) and (1d) by acting 
an eliminating agent for R.sup.4a and R.sup.5a on Compounds (1b) and (1a) 
in an inert solvent to remove the substituent on the amino group, as 
necessary. 
While the solvent employable in the reaction of eliminating R.sup.4a and 
R.sup.5a is not particularly limited unless it inhibits the reaction, 
there may be mentioned preferably ethers such as tetrahydrofuran and 
dioxane. The reagent employable is not particularly limited as long as it 
is usually used for eliminating a silyl group, and there may be mentioned 
one which forms a fluorine anion such as tetrabutylammonium fluoride. 
Reaction is carried out at a temperature of 0.degree. C. to 40.degree. C. 
preferably at room temperature. 
While the reaction time varies depending on the reaction temperature. it is 
from 10 minutes to 24 hours, preferably 1 hour to 5 hours. 
The desired compound thus obtained can be collected, separated and purified 
by combining suitably various methods. For example, the reaction mixture 
is poured into water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene. ether and ethyl acetate, and the 
solvent is distilled off from the extract to obtain the Compound (8). If 
necessary, thus obtained compound can further be subjected, for example, 
to adsorption or ion exchange chromatography using various carriers such 
as an activated carbon and silica gel, gel filtration using a Cephadex 
column or recrystallization using an organic solvent such as ether, ethyl 
acetate and chloroform. 
Incidentally, in the case where R.sup.2 is a substituted amino group, it 
can sometimes be eliminated simultaneously. 
(Steps 11 and 13) 
These steps are for preparing Compounds (1c) and (1d) of the present 
invention by acting an eliminating agent for the protective group to 
eliminate the substituent on R.sup.2 in an inert solvent. and this step is 
selected if desired. 
While the elimination of the protective moiety varies depending on the 
protective moiety, it is usually carried out by a method known in the art 
as follows: 
a) In the case where the protective moiety is an aliphatic acyl, an 
aromatic acyl or an alkyloxycarbonyl: such protective moiety can be 
removed by treating with an acid in the presence or absence of a solvent. 
As the acid employable, there may be mentioned hydrochloric acid, acetic 
acid, sulfuric acid, phosphoric acid and hydrobromic acid, preferably 
acetic acid. 
As the solvent employable, there may be mentioned alcohols such as 
methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, 
t-butanol, isoamyl alcohol, diethylene glycol, glycerol and octanol, 
aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as 
tetrahydrofuran and dioxane, and a mixed solvent of such organic solvent 
and water. 
Reaction is carried out at a temperature of 0.degree. C. to 40.degree. C., 
preferably at room temperature. 
While the reaction time varies depending on the reaction temperature, it is 
from 10 minutes to 24 hours, preferably 1 hour to 5 hours. 
The desired compound thus obtained can be collected, separated and purified 
by combining suitably various methods. Usually, the reaction mixture is 
distilled off and the residue is subjected, for example, to adsorption or 
ion exchange chromatography using various carriers such as an activated 
carbon and silica gel, gel filtration using a Cephadex column or 
recrystallization using an organic solvent such as ether, ethyl acetate 
and chloroform. 
b) In the case where the protective moiety is an aralkyloxycarbonyl: such 
protective moiety can be eliminated by catalytical reduction using a 
catalyst. 
As the solvent employable, there may be mentioned alcohols such as 
methanol, ethanol, n-propanol, isopropanol and n-butanol, saturated 
hydrocarbons such as hexane and cyclohexane, ethers such as 
tetrahydrofuran and dioxane, and lower fatty acids such as acetic acid and 
propionic acid, preferably methanol, ethanol, acetic acid and propionic 
acid. 
As the catalyst employable, there may preferably be mentioned platinum and 
palladium on carbon. 
Reaction is carried out at a temperature of 0.degree. C. to 40.degree. C., 
preferably at room temperature. 
While the reaction time varies depending on the reaction temperature, it is 
from 10 minutes to 24 hours, preferably 1 hour to 5 hours. 
The desired compound thus obtained can be collected, separated and purified 
by combining suitably various methods. Usually, the reaction mixture is 
distilled off and the residue is subjected, for example, to adsorption or 
ion exchange chromatography using various carriers such as an activated 
carbon and silica gel, gel filtration using a Cephadex column or 
recrystallization using an organic solvent such as ether, ethyl acetate 
and chloroform. 
(Step 14) 
This step is for preparing Compound (10) by acting a protecting reagent on 
Compound (1d) in an inert solvent. 
As the solvent employable, there may be mentioned basic solvents such as 
pyridine and neutral solvents such as benzene, toluene and ether. 
While the protecting reagent employable is not particularly limited as long 
as it can specifically protect only the hydroxyl group at the 5'-position, 
triphenylchloromethane, monomethoxytrityl chloride, dimethoxytrityl 
chloride, etc. can suitably be used. 
Reaction is usually carried out at a temperature of 0.degree. C. to 
100.degree. C., preferably -10.degree. C. to 50.degree. C. 
The reaction time is usually from 30 minutes to 10 hours, preferably 1 hour 
to 5 hours. 
When a neutral solvent is used as the solvent, an organic amine such as 
triethylamine can be used in order to carry out the reaction efficiently. 
The compound thus obtained can be collected, separated and purified by 
combining suitably various methods. For example, the reaction mixture is 
poured into water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene, ether and ethyl acetate, and the 
solvent is distilled off from the extract to obtain the desired compound. 
If necessary. thus obtained compound can be subjected. for example, to 
adsorption or ion exchange chromatography using various carriers such as 
an activated carbon and silica gel, gel filtration using a Cephadex column 
or recrystallization using an organic solvent such as ether. ethyl acetate 
and chloroform. 
(Step 15) 
This step is for preparing Compound (11) by acting a hydroxyl group 
eliminating agent on Compound (10) in an inert solvent. 
As the solvent employable, there may be mentioned. for example, aliphatic 
hydrocarbons such as hexane, heptane, ligroin and petroleum ether, 
aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as 
diethyl ether, diisopropyl ether, tetrahydrofuran. dioxane, 
dimethoxyethane and diethylene glycol dimethyl ether, ketones such as 
acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and 
cyclohexanone, nitro compounds such as nitroethane and nitrobenzene, 
nitriles such as acetonitrile and isobutyronitrile, amides such as 
formamide, dimethylformamide, dimethylacetamide and hexamethyl 
phophorotriamide and sulfoxides such as dimethyl sulfoxide and sulfolane, 
preferably aromatic hydrocarbons such as benzene. toluene and xylene. 
As the reagent employable, there may be mentioned compounds having a 
thiocarbonyl group such as thiocarbonyl diimidazole and 
phenoxythiocarbonyl chloride. 
Reaction is carried out at a temperature of -10.degree. C. to 50.degree. 
C., preferably at room temperature. 
The reaction time is usually from 1 hour to 24 hours, preferably 3 hours to 
10 hours. 
The desired compound thus obtained can be collected, separated and purified 
by combining suitably various methods. For example, the reaction mixture 
is poured into water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene, ether and ethyl acetate, and the 
solvent is distilled off from the extract to obtain the desired compound. 
If necessary, thus obtained compound can be subjected, for example, to 
adsorption or ion exchange chromatography using various carriers such as 
an activated carbon and silica gel, gel filtration using a Cephadex column 
or recrystallization using an organic solvent such as ether, ethyl acetate 
and chloroform. 
(Step 16) 
This step is for preparing the desired Compound (2a) of the present 
invention by acting a hydroxyl group deprotecting agent on Compound (11) 
in an inert solvent. 
While the elimination of the protecting moiety varies depending on the 
protecting moiety, it is usually carried out by a method known in the art, 
and in the case where the protecting moiety is a triarylmethyl which is a 
preferable protective group, it is carried out as follows: 
While the solvent employable is not particularly limited unless it 
participates in this reaction, it preferably includes alcohols such as 
methanol and ethanol, ethers such as tetrahydrofuran and dioxane, and 
mixed solvent with such organic solvent with water. 
The reagent to be used is usually an acid. The acid is not particularly 
limited as long as it is used as a Br.o slashed.nsted acid, and preferably 
includes an inorganic acid such as hydrochloric acid and sulfuric acid, 
and an organic acid such as acetic acid and P-toluenesulfonic acid. In 
addition, a strong acidic cation exchange resin such as Dowex 50W can be 
used. 
Reaction is usually carried out at a temperature of 0.degree. C. to 
50.degree. C., preferably at room temperature. 
While the reaction time varies depending on the starting materials, types 
of acids, etc., it is usually from 10 minutes to 18 hours, preferably 30 
minutes to 5 hours. 
The desired compound thus obtained can be collected, separated and purified 
by combining suitably various methods. For example, the reaction mixture 
is poured into water, the resulting mixture is extracted with a 
water-immiscible solvent such as benzene, ether and ethyl acetate, and the 
solvent is distilled off from the extract to obtain the desired compound. 
If necessary, thus obtained compound can be subjected, for example, to 
adsorption or ion exchange chromatography using various carriers such as 
an activated carbon and silica gel, gel filtration using a Cephadex column 
or recrystallization using an organic solvent such as ether, ethyl acetate 
and chloroform. 
[Best Mode for Practicing the Invention]

The present invention is described further in detail by way of Examples, 
Reference Examples and Preparation Examples. In Examples, TIPDS stands for 
(1,1,3,3-tetraisopropyl disilox-1,3-diyl). 
EXAMPLE 1 
1-[2'-Cyano-3',5'-O-(1,1,3,3-tetraisopropyldisilox-1,3-diyl)-.beta.-D-ribof 
uranosyl]thymine 
In 15 ml of ether-water (2:1) was dissolved 997 mg of 
1-(3,5-O-TIPDS-.beta.-D-erythro-pentofuran-2-urosyl)thymine, and to the 
resulting solution were added 196 mg of sodium cyanide and 336 mg of 
sodium hydrogencarbonate, followed by stirring at room temperature for 36 
hours. After completion of the reaction, to the reaction mixture was added 
ethyl acetate, and the mixture was washed three times with water. The 
ethyl acetate layer was dried over anhydrous sodium sulfate and the 
solvent was removed by evaporation. The residue was purified over column 
chromatography using a silica gel column (.phi.2.4.times.9.5 cm) (eluted 
with hexane/ethyl acetate (2:1)) to obtain 1.03 g (97.5%) of the title 
compound as a white foam. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 9.20 and 8.52(1H, bs) 7.43 and 
7.36(1H, d, J=6.8 Hz) 6.22 and 6.00(1H, s) 5.08(1H, bs) 4.32-3.94(4H, m) 
1.92(3H, d, J=1.7 Hz) 1.12-1.07(28H, m) 
EXAMPLE 2 
1-(2'-Cyano-2'-deoxy-3',5'-O-TIPDS-.beta.-D-arabinofuranosly)thymine 
In 2 ml of anhydrous acetonitrile were dissolved 100 mg of the compound of 
Example 1 and 10 mg of 4,4-dimethylaminopyridine (hereinafter abbreviated 
as DMAP), and to the resulting solution were added 39 .mu.l of 
phenoxycarbonyl chloride and 40 .mu.l of triethylamine at 0.degree. C. in 
an argon gas stream, followed by stirring for 3 hours. After completion of 
the reaction, ethyl acetate was added to the reaction mixture and the 
mixture was washed three times with water. The mixture was dried over 
anhydrous sodium sulfate, and the solvent was removed by evaporation. The 
residue was purified over column chromatography using a silica gel column 
(.omega.1.6.times.10 cm) (eluted with methanol/chloroform (1:99)) to 
obtain 71 mg (73.3%) of the title compound as a yellowish white foam. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 7.36(1H, d, J=1.2 Hz) 6.28(1H, d, 
J=7.3 Hz) 4.67(1H, dd, J=8.3, 9.3 Hz) 4.17(1H, dd, J=2.2, 13.2 Hz) 
4.04(1H, dd, J=2.9, 13.2 Hz) 3.78(1H, ddd, J=2.2, 2.9, 8.3 Hz) 3.58(1H, 
dd, J=7.3, 9.3 Hz) 1.94(1H, d, J=1.2 Hz) 1.15-1.04(28H, m) 
EXAMPLE 3 
1-(2'-Cyano-2'-deoxy-.beta.-D-arabinofuranosyl)thymine 
In 3 ml of anhydrous tetrahydrofuran (THF) was dissolved 178 mg of the 
compound of Example 2, and to the resulting solution were dropwise added 
20 .mu.l of acetic acid and 0.70 ml of a solution of tetrabutylammonium 
fluoride in 1M-THF at 0.degree. C. in an argon gas stream, followed by 
stirring for 1.5 hours. After completion of the reaction, the reaction 
mixture was concentrated, purified over column chromatography using a 
silica gel column (.phi.1.8.times.8 cm) (eluted with ethanol/chloroform 
(8-10: 92-90)) and crystallized from ether and ethanol to obtain 27 mg of 
the title compound as white crystals. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 11.49(1H, s) 7.85(1H, d, J=1.1 Hz) 
6.25(1H, d, J=6.0 Hz) 6.20(1H, d, J=7.1 Hz) 5.30(1H, t, J=4.9 Hz) 4.47(1H, 
ddd, J=6.0, 8.2, 8.8 Hz) 3.89(1H, dd, J=7.1, 8.8 Hz) 3.74(1H, ddd, J=2.2, 
3.3, 8.2 Hz) 3.62(1H, ddd, J=3.3, 4.9, 11.1 Hz) 1.78(3H, d, J=1.1 Hz) 
EXAMPLE 4 
1-(2'-Cyano-2'-deoxy-3'-O-TIPDS-.beta.-D-arabinofuranosyl)-N.sup.4 
-benzoylcytosine 
The procedures in Example 1 were analogously repeated using 294 mg of 
N.sup.4 
-benzoyl-1-(3,5-O-TIPDS-.beta.-D-erythropentofuran-2-urosyl)cytosine. 
Further, the procedures in Example 2 were analogously repeated using the 
resulting crude product to obtain 174 mg (49.1%) of the title compound as 
a yellowish white solid. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 8.89(1H, bs) 8.11(1H, d, J=7.7 Hz) 
7.93-7.45(5H, m) 7.67(1H, d, J=7.7 Hz) 6.36(1H, d, J=6.6 Hz) 4.67(1H, t, 
J=8.1 Hz) 4.18(1H, dd, J=2.9, 13.2 Hz) 4.10(1H, dd, J=2.9, 13.2 Hz) 
3.91(1H, ddd, J=2.9, 2.9, 8.1 Hz) 3.75(1H, dd, J=6.6, 8.1 Hz) 
1.15-1.04(28H, m) 
EXAMPLE 5 
1-(2'-Cyano-2'-deoxy-.beta.-D-arabinofuranosyl)-N.sup.4 -benzoylcytosine 
The procedures in Example 3 were analogously repeated using 100 mg of the 
compound of Example 4 and crystallization from methanol was carried out to 
obtain 25 mg of the title compound as white crystals. 
.sup.1 H-NMR(DMSO-d.sub.6) .delta. ppm: 11.34(1H, bs) 8.45(1H, d, J=7.7 Hz) 
8.00(2H, m) 7.66-7.49(3H, m) 7.42(1H, d, J=7.7 Hz) 6.29(1H, d, J=5.5 Hz) 
6.25(1H, d, J=7.1 Hz) 5.28(1H, bs) 4.47(1H, ddd, J=5.5, 7.1, 7.7Hz) 
3.94(1H, dd, J=7.1, 7.7Hz) 3.86(1H, ddd, J=2.5, 3.8, 7.1 Hz) 3.79(1H, bd, 
J=12.5Hz) 3.65(1H, bd, J=12.5Hz) 
EXAMPLE 6 
1-(2'-Cyano-2'-deoxy-3',5'-O-TIPDS-.beta.-D-arabinofuranosyl)-N.sup.4 
-acetylcytosine 
The procedures in Example 4 were analogously repeated using 2 g of N.sup.4 
-acetyl-1-(3,5-O-TIPDS-.beta.-D-erythropentofuran-2-urosyl)cytosine, and 
after purification, the crystals obtained by evaporation of the solvent 
were collected by filtration with ether-hexane to obtain 703 mg of the 
title compound as white crystals. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 9.92(1H, bs) 8.07(1H, d, J=7.7 Hz) 
7.55(1H, d, J=7.7 Hz) 6.34(1H, d, J=7.0 Hz) 4.63(1H, t, J=8.8 Hz) 4.18(1H, 
dd, J=2.4, 13.4 Hz) 4.06(1H, dd, J=2.7, 13.4 Hz) 3.89(1H, ddd, J=2.4, 2.7, 
8.8 Hz) 3.72(1H, dd, J=7.0, 8.8 Hz) 2.30(3H, s) 1.13-1.03(28H, m) 
EXAMPLE 7 
1-(2'-Cyano-2'-deoxy-.beta.-D-arabinofuranlyl)-N.sup.4 -acetylcytosine 
The procedures in Example 3 were analogously repeated using 1.07 g of the 
compound of Example 6, and after purification, the crystals obtained by 
evaporation of the solvent were collected by filtration with ether-hexane 
to obtain 480 mg of the title compound as white crystals. 
.sup.1 H-NMR (DMSO-d.sub.6) .delta. ppm: 10.97(1H, bs) 8.36(1H, d, J=7.7 
Hz) 7.26(1H, d, J=7.7 Hz) 6.27(1H, d, J=6.1 Hz) 6.22(1H, d, J=7.1 Hz) 
5.24(1H, bs) 4.43(1H, ddd, J=6.1, 7.1, 7.1 Hz) 3.92(1H, t, J=7.1 Hz) 
3.84(1H, ddd, J=2.8, 3.3, 7.1 Hz) 3.76(1H, bd, J=12.1 Hz) 3.63(1H, bd, 
J=12.1 Hz) 2.11(3H, s) 
EXAMPLE 8 
1-(2'-Cyano-2'-deoxy-.beta.-D-arabinofuranosyl)cytosine 
In 55 ml of methanol was dissolved 100 mg of the compound of Example 7, and 
to the resulting solution was added 2.5 ml of acetic acid, followed by 
refluxing with heating in an oil bath for 5 days. After completion of the 
reaction, the solvent was evaporated and the residue was purified over a 
silica gel column (.phi.1.8.times.7 cm) (eluted with methanol/chloroform 
(12-15:88-85)) and further over HPLC (D-ODS-5.5% methanol-water) and then 
crystallized from ethanol-ether to obtain 29 mg of the title compound as 
white crystals. 
.sup.1 H-NMR(DMSO-d.sub.6) .delta. ppm: 7.83(1H, d, J=7.1 Hz) 7.27(2H, bs) 
6.17(1H, d, J=6.6 Hz) 6.15(1H, d, J=7.1 Hz) 5.79(1H, d, J=7.6 Hz) 5.14(1H, 
t, J=4.9 Hz) 4.40(1H, ddd, J=6.6, 7.1, 7.7 Hz) 3.77(1H, t, J=7.1 Hz) 
3.74(1H, ddd, J=2.8, 4.5, 7.7 Hz) 3.73(1H, ddd, J=2.8, 4.9, 12.6 Hz) 
3.60(1H, ddd, J=2.8, 4.9, 12.6 Hz) 
EXAMPLE 9 
1-(2'-Cyano-2'-deoxy-.beta.-D-arabinofuranosyl)cytosine.monohydrochloride 
In 5 ml of 3% hydrochloric acid-methanol was dissolved 40 mg of the 
compound of Example 8, followed by stirring at room temperature for 50 
minutes. After completion of the reaction, crystallization was carried out 
using ethanol-ether to obtain 26 mg of the title compound as white 
crystals. 
.sup.1 H-NMR(DMSO-d.sub.6) .delta. ppm: 9.80(1H, s) 8.75(1H, s) 8.30(1H, d, 
J=7.7 Hz) 6.21(1H, d, J=7.2 Hz) 6.12(1H, d, J=7.7 Hz) 4.43(1H, dd, J=7.1, 
7.7 Hz) 3.97(1H, t, J=7.1 Hz) 3.83(1H, ddd, J=2.8, 3.3, 7.7 Hz) 3.76(1H, 
dd, J=2.8, 12.6 Hz) 3.62(1H, dd, J=3.8, 12.6 Hz) 
EXAMPLE 10 
1-(2'-Cyano-2'-deoxy-3',5'-O-TIPDS-.beta.-D-ribofuranosyl)thymine 
In 4 ml of anhydrous toluene was suspended 400 mg of 
3',5'-O-TIPDS-2'-O-phenoxythiocarbonylthymidine, and to the resulting 
suspension was added 1.98 ml of t-butylisonitrile, followed by heating in 
an oil bath at 100.degree. C. in an argon gas stream. To the resulting 
mixture was dropwise added 4 ml of a solution of azoisobutyronitrile (50 
mg) and tributyltin hydride (0.25 ml) in toluene over an hour using a 
syringe pump. After three hours from the completion of the dropwise 
addition, 0.25 ml of tributyltin hydride was added to the mixture, and the 
mixture was stirred for 19 hours, followed by evaporation of the solvents. 
The residue was purified over column chromatography using a silica gel 
column (2.2.times.8 cm) (eluted with chloroform) to obtain 70 mg of the 
title compound as a yellow foam. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 8.57(1H, bs) 7.38(1H, d, J=1.1 Hz) 
6.01(1H, d, J=2.6 Hz) 4.22-4.01(4H, m) 3.48(1H, dd, J=2.6, 4.8 Hz) 
1.90(3H, d, J=1.1 Hz) 1.10-1.01(28H, m) 
EXAMPLE 11 
1-(2'-Cyano-2'-deoxy-.beta.-D-ribofuranosyl)thymine 
The procedures in Example 3 were analogously repeated using 70 mg of the 
compound of Example 10, and after purification, the solid obtained by 
evaporating the solvent was collected by filtration with ether to obtain 
17 mg of the title compound as a yellowish white solid. 
.sup.1 H-NMR(DMSO-d.sub.6) .delta. ppm: 11.49(1H, bs) 7.64(1H, d, J=1.1 Hz) 
6.32(1H, d, J=5.5 Hz) 6.27(1H, d, J=8.2 Hz) 5.22(1H, bs) 4.37(1H, ddd, 
J=2.8, 5.5, 5.5 Hz) 3.93(1H, m) 3.75(1H, dd, J=5.5, 8.2 Hz) 3.66-3.51(2H, 
m) 1.78(3H, d, J=1.1 Hz) 
EXAMPLE 12 
1-(2'-Cyano-2',3'-deoxy-2',3'-didehydro-.beta.-D-ribofuranosyl)thymine 
In 3 ml of acetic acid was dissolved 112 mg of the compound of Reference 
example 3 and the resulting solution was stirred at room temperature for 1 
hour. After completion of the reaction, the solvent was evaporated and the 
residue was purified over a silica gel column (.phi.1.6.times.8.5 cm) 
(eluted with ethanol/chloroform =8:92). The solvent was evaporated and the 
crystals precipitated were collected by filtration using ether-hexane to 
obtain 22 mg of the title compound as crystals. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 11.53(1H, bs) 7.81(1H, d, J=1.1 Hz) 
7.63(1H, d, J=1.7 Hz) 7.02(1H, dd, J=1.7, 3.9 Hz) 5.33(1H, t, J=4.9 Hz) 
5.05(1H, ddd, J=2.8, 2.8, 3.9 Hz) 3.74(1H, ddd, J=2.8, 4.9, 12.6 Hz) 
3.67(1H, ddd, J=2.8, 4.9, 12.6 Hz) 1.75(3H, d, J=1.1 Hz) 
EXAMPLE 13 
1-(2'-Cyano-2',3'-dideoxy-2',3'-didehydro-.beta.-D-arabinofuranosyl)-N.sup. 
4 -acetylcytosine 
The procedures in Example 12 were analogously repeated using 70 mg of the 
compound of Reference example 4. After purification over a silica gel 
column (.phi.1.8.times.7 cm) (eluted with methanol/chloroform =10:90), 
crystallization from ethanol-ether was carried out to obtain 14 mg of the 
title compound as crystals. 
.sup.1 H-NMR(DMSO-d.sub.6) .delta. ppm: 11.02(1H, s) 8.33(1H, d, J=7.1 Hz) 
7.65(1H, t, J=1.7 Hz) 7.24(1H, d, J=7.1 Hz) 7.12(1H, dd, J=1.7, 3.3 Hz) 
5.30(1H, t, J=4.9 Hz) 5.12(1H, m) 3.74(1H, dd, J=3.3, 12.6 Hz) 3.67(1H, 
dd, J=3.3, 12.6 Hz) 2.12(3H,s) 
EXAMPLE 14 
N.sup.4 -Benzyloxycarbonylcytidine 
In pyridine was dissolved 4.86 g of cytidine as much as possible, and the 
resulting solution was subjected to azeotropic distillation twice to 
remove the moisture content therefrom. To the residue was added 100 ml of 
pyridine, and 12.6 ml of trimethylchlorosilane was added to the resulting 
mixture under ice-cooling, followed by stirring for 30 minutes. 49 ml of 
carbobenzoxychloride (30 to 35% toluene solution) was dropwise added to 
the resulting mixture. After the mixture was stirred at room temperature, 
the mixture was left to stand overnight. To the mixture was added 40 ml of 
water and the resulting mixture was stirred for 1.5 hours. After addition 
of methylene chloride, the organic layer was separated and washed with a 
saturated aqueous sodium chloride. The organic layer was then dried over 
anhydrous magnesium sulfate and the solvent was evaporated. The residue 
was subjected to azeotropic distillation three times with toluene and 
ethanol to obtain 6.13 g of the title compound as a crystalline residue. 
.sup.1 H-NMR(270MHz in d6-DMSO) .delta. ppm: 8.40(1H, d, J=7.3 Hz), 
7.31-7.55(5H, m), 7.02(1H, d, J=7.3 Hz), 5.77(1H, d, J=2.4 Hz), 5.19(2H, 
s), 3.88-3.99(3H, m) 
EXAMPLE 15 
3',5'-O-TIPDS-N.sup.4 -benzyloxycarbonylcytidine 
In pyridine was dissolved 6.0 g of the compound of Example 14, and the 
resulting solution was subjected to azeotropic distillation twice to 
remove the moisture content therefrom. The residue was dissolved in 200 ml 
of pyridine, and 5.09 ml of 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane 
was added thereto, followed by stirring at room temperature. After the 
mixture was left to stand for 2 days, the solvents were evaporated. The 
residue was dissolved in methylene chloride, and the solution was washed 
successively with water, 0.5N hydrochloric acid, a saturated aqueous 
sodium chloride, a saturated aqueous sodium hydrogencarbonate and a 
saturated aqueous sodium chloride. The residue was dried over anhydrous 
sodium sulfate, and the solvent was evaporated to obtain 10.23 g of the 
title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 10.83(1H, bs), 8.12(1H, 
d, J=7.8 Hz), 7.32-7.43(5H, m), 7.03(1H, d, J=7.3 Hz), 5.59(1H, s), 
5.19(1H, s), 3.91-4.24(5H, m), 0.80-1.14(28H, m) 
EXAMPLE 16 
N.sup.4 
-Benzyloxycarbonyl-1-(3,5-O-TIPDS-.beta.-D-erythropentofuran-2-urosyl)cyto 
sine 
To 70 ml of methylene chloride were added 13.16 g of pyridinium dichromate, 
3.31 ml of acetic anhydride, 0.94 ml of pyridine and 2.5 g of cellite, and 
the resulting mixture was stirred for 40 minutes. Separately, 7.23 g of 
the compound of Example 15 was dissolved in 30 ml of methylene chloride, 
and the resulting solution was added to the above prepared mixture. After 
thus obtained mixture was stirred at room temperature for 5 hours, ethyl 
acetate was added thereto and methylene chloride was distilled off. The 
residue was dissolved in ethyl acetate and insolubles were filtered off. 
After the filtrate was washed with 1N hydrochloric acid, a saturated 
aqueous sodium chloride, a saturated aqueous sodium hydrogencarbonate and 
a saturated aqueous sodium chloride, the filtrate was dried over anhydrous 
magnesium sulfate. The solvent was distilled off and the residue was 
purified over silica gel chromatography (methylene chloride/methanol=99:1) 
to obtain 2.84 g of the title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 10.98(1H, bs), 8.15(1H, 
d, J=7.3 Hz), 7.32-7.44(5H, m), 7.09(1H, d, J=7.3 Hz), 5.49(1H, s), 
5.20(2H, s), 5.07(1H, d, J=8.3 Hz), 3.95-4.04(3H, m), 0.92-1.12(28H, m) 
EXAMPLE 17 
N.sup.4 
-Benzyloxycarbonyl-2'-Cyano-3',5'-O-TIPDS-.beta.-D-arabinofuranosyl-cytosi 
ne 
In 25 ml of tetrahydrofuran was dissolved 2.71 g of the compound of Example 
16, and 13 ml of water was added thereto, followed by stirring. To the 
resulting mixture was added 436 mg of sodium cyanide under ice-cooling. 
Then, 740 mg of sodium hydrogencarbonate was added to the mixture, 
followed by stirring at room temperature for 7 hours. After the mixture 
was left to stand in a refrigerator overnight, 217 mg of sodium cyanide 
was further added thereto. The resulting mixture was stirred at room 
temperature for 8 hours, and after the solvents were distilled off, the 
residue was dissolved in ethyl acetate. The solution was washed three 
times with a saturated aqueous sodium chloride and dried over anhydrous 
magnesium sulfate, followed by evaporation of the solvent. The residue was 
purified over silica gel chromatography (eluted with methylene 
chloride/methanol=9.25:0.75)) and crystallized from acetonitrile to obtain 
392 mg of the title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 11.00(1H, bs), 8.05(1H, 
d, J=7.3 Hz), 7.83(1H, bs), 7.33-7.44(5H, m), 7.13(1H, d, J=7.8 Hz), 
5.93(1H, s), 5.21(2H, s), 3.93-4.33(4H, m), 0.96-1.07(28H, m) 
EXAMPLE 18 
N.sup.4 
-Benzyloxycarbonyl-2'-cyano-deoxy-3',5'-O-TIPDS-.beta.-D-arabinofuranosylc 
ytosine 
In 8 ml of toluene was dissolved 0.40 g of the compound of Reference 
example 5, and to the resulting solution were added 13.4 mg of 
.alpha.,.alpha.'-azobisisobutyronitrile and 0.20 ml of tributyltin hydride 
in this order in a nitrogen gas stream, followed by stirring at 
100.degree. C. for 2 hours. The solvent was distilled off and the residue 
was purified over silica gel chromatography (eluted with methylene 
chloride/methanol=9:1) to obtain 202 mg of the title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 10.96(1H, bs), 8.02(1H, 
d, J=7.3 Hz), 7.32-7.44(5H, m), 7.12(1H, d, J=7.8 Hz), 6.20(1H, d, J=7.8 
Hz), 5.20(2H, s), 3.91-4.72(5H, m), 0.95-1.23(28H, m) 
EXAMPLE 19 
N.sup.4 
-Benzyloxycarbonyl-2'-cyano-2'-deoxy-.beta.-D-arabinofuranosycytosine 
In 5 ml of tetrahydrofuran was dissolved 192 mg of the compound of Example 
18, and after the resulting solution was ice-cooled in a nitrogen gas 
stream, a solution of 0.02 ml of-acetic acid and 168 mg of 
tetrabutylammonium fluoride dissolved in 1.2 ml of tetrahydrofuran was 
added thereto, followed by stirring under ice-cooling for 2 hours. The 
solvents were distilled off and the residue was purified over silica gel 
chromatography (eluted with methylene chloride/methanol=95:5) to obtain 94 
mg of the title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 10.92(1H, bs), 8.36(1H, 
d, J=7.3 Hz), 7.34-7.44(5H, m), 7.11(1H, d, J=7.8 Hz), 6.25(1H, d, J=5.4 
Hz), 6.20(1H, d, J=6.8 Hz), 5.24(1H, d, J=4.4 Hz), 5.20(2H, s), 4.43(1H, 
q, J=7.3, 12.7 Hz), 3.61-3.93(4H, m) 
EXAMPLE 20 
2'-Cyano-2',3'-dideoxy-2',3'-didehydro-.beta.-D-ribofuranosylcytosine 
The synthetic procedures for the compound of Example 12 was analogously 
repeated using 300 mg of the compound of Example 8 to obtain 60 mg of the 
title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 7.79(1H, d, J=7.3 Hz), 
7.55-7.56(1H, m), 7.36(2H, d, J=7.3 Hz), 7.07(1H, dd, J=1.96, 3.90 Hz), 
5.78(1H, d, J=7.3 Hz), 5.18-5.21(1H, m), 5.01-5.03(1H, m), 3.65-3.70(2H, 
m) 
Reference Example 1 
1-[2'-Cyano-2'-deoxy-5'-O-(4,4'-dimethoxytriphenylmethyl)-.beta.-D-arabinof 
uranosyl]thymine 
In 7 ml of anhydrous pyridine was dissolved 267 mg of the compound of 
Example 3 and to the resulting solution was added 508 mg of 
4,4'-dimethoxytriphenylmethyl chloride, followed by stirring at room 
temperature for 1.5 hours in an argon gas stream. After completion of the 
reaction, the solvent was distilled off, and 100 ml of ethyl acetate was 
added to the residue. After the mixture was washed three times with 50 ml 
of water and dried over anhydrous sodium sulfate, the solvent was 
evaporated. The residue was purified over a silica gel column 
(.phi.1.8.times.8.5 cm) (eluted with ethanol/chloroform=1-2:99-88) to 
obtain 574 mg of the title compound as a yellowish white foam. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 8.40(1H, bs) 7.50(1H, d, J=1.2 Hz) 
4.77-7.26(9H, m) 6.90-6.80(4H, m) 6.27(1H, d, J=6.8 Hz) 4.74(1H, d, J=6.8 
Hz) 3.93(1H, m) 3.79(6H, s) 3.62(1H, m) 3.61(1H, m) 3.30(2H, m) 1.67(1H, 
d, J=1.2 Hz) 
Reference Example 2 
1-[2'-Cyano-2'-deoxy-5'-O-(4,4'-dimethoxytriphenylmethyl)-.beta.-D-arabinof 
uranosyl]-N.sup.4 -acetycytosine 
The procedures in Reference Example 1 were repeated analogously using 194 
mg of the compound of Example 7 to obtain 326 mg of the title compound as 
a yellowish white foam. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 8.80(1H, bs) 8.19(1H, d, J=7.6 Hz) 
7.41-7.14 and 6.89-6.76(14H, m) 6.30(1H, d, J=6.1 Hz) 4.79(2H, m) 4.08(2H, 
m) 3.79(6H, s) 3.56(2H, m) 2.09(3H, s) 
Reference Example 3 
1-[2-Cyano-2',3'-dideoxy-2',3'-didehydro-5'-O-(4 
4'-dimethoxytriphenylmethyl)-.beta.-D-ribofuranosyl]thymine 
In 3 ml of anhydrous dimethylformamide was dissolved 200 mg of the compound 
of Reference example 1, and to the resulting solution was added 94 mg of 
thiocarbonyldiimidazole, followed by stirring at room temperature for 13 
hours and 40 minutes in an argon gas stream. After completion of the 
reaction, ethyl acetate was added to the reaction mixture, and the mixture 
was washed three times with water and dried over anhydrous sodium sulfate, 
followed by evaporation of the solvents. The residue was purified over a 
silica gel column (2.phi..times.6.5 cm) (eluted with hexane/ethyl 
acetate=1:1 to 1:2) to obtain 162 mg of the title compound as a white 
caramel. 
.sup.1 H-NMR(CDCl.sub.3) .delta. ppm: 8.40(1H, bs) 7.45(1H, d, J=1.1 Hz) 
7.10(1H, d, J=1, 8 Hz) 7.06(1H, dd, J=1.8, 4.0 Hz) 5.10(1H, ddd, J=2.6, 
3.3, 4.0 Hz) 4.12(3H, s) 3.61(1H, dd, J=2.6, 11.0 Hz) 3.45(1H, dd, J=3.3, 
11.0 Hz) 1.90(3H, d, 
J=1.1 Hz) 
Reference Example 4 
1-[2'-Cyano-2',3'-dideoxy-2',3'-didehydro-5'-O-(4,4'-dimethoxytriphenylmeth 
yl)-.beta.-D-arabinofuranosyl]-N.sup.4 -acetylcytosine 
The procedures in Reference example 3 were repeated analogously using 326 
mg of the compound of Reference example 2, and after purification, 
crystallization from ether was carried out to obtain 163 mg of the title 
compound as crystals. 
.sup.1 H-NMR(DMSO-d.sub.6) .delta. ppm: 9.22(1H, s) 8.16(1H, d, J=7.3 Hz) 
7.35-7.22(9H, m) 6.95(1H, dd, J=l.8, 4.0 Hz) 6.90-6.84(5H, m) 6.68(1H, dt, 
J=1.8) 5.08(1H, ddd, J=2.6, 2.9, 4.0 Hz) 3.82(6H, s) 3.71(1H, dd, J=2.9, 
11.7 Hz) 3.59(1H, dd, J=2.6, 11.7 Hz) 2.24(3H, s) 
Reference Example 5 
N.sup.4 
-Benzyloxycarbonyl-2'-cyano-2'-phenoxythiocarbonyl-3',5'-O-TIPDS-.beta.-D- 
arabinofuranosyl-cytosine 
In pyridine was dissolved 525 mg of the compound of Example 17, and after 
the moisture content was removed by azeotropic distillation, the residue 
was dissolved in 5 ml of methylene chloride. To the resulting solution 
were added 40 mg of dimethylaminopyridine, 0.17 ml of phenyl 
chlorothionoformate and 0.17 ml of triethylamine in this order under 
ice-cooling in a nitrogen gas stream, and the mixture was stirred for 4 
hours under ice-cooling. Methylene chloride was added to the reaction 
mixture, and after the resulting mixture was washed with a saturated 
aqueous sodium chloride, 0.1N hydrochloric acid and a saturated aqueous 
sodium chloride and dried over anhydrous magnesium sulfate, the solvents 
were evaporated. The residue was purified over silica gel chromatography 
(eluted with methylene chloride/methanol=99.5:0.5) to obtain 0.46 g of the 
title compound. 
.sup.1 H-NMR(270MHz in d.sub.6 -DMSO) .delta. ppm: 11.02(1H, bs), 8.00(1H, 
d, J=7.8 Hz), 7.31-7.98(10H, m), 7.11(1H, d, J=7.8 Hz), 6.29(1H, s), 
5.75(1H, bs), 5.20(2H, s), 3.98-4.17(3H, m), 1.00-1.12(28H, m) 
(Preparation example 1) 
Hard capsules 
In each piece of standard cap-and-body type hard gelatin capsules were 
charged 100 mg of the powdery complex of Example 1, 150 mg of lactose, 50 
mg of cellulose and 6 mg of magnesium stearate to prepare unit capsules. 
The thus obtained capsules were washed and dried to provide hard capsule 
preparations. 
(Preparation example 2) 
Tablets 
Tablets were prepared by mixing 100 mg of the complex of Example 1, 0.2 g 
of colloidal silicon dioxide, 5 mg of magnesium stearate, 275 mg of 
microcrystalline cellulose, 11 mg of starch and 98.8 mg of lactose, and 
pelletizing the mixture. 
Incidentally, coating was applied to the tablets, if desired. 
(Preparation example 3) 
Injections 
In 10% by volume of propylene glycol was stirred 1.5% by weight of the 
complex of Example 1. The mixture was then made to a predetermined volume 
with a distilled water for injection, followed by sterilization to obtain 
an injection. 
(Preparation example 4) 
Suspension 
To 5 ml were admixed 100 mg of the micropowdery complex of Example 1, 100 
mg of sodium carboxymethyl cellulose, 5 mg of sodium benzoate, 1.0 g of 
sorbitol solution (The Pharmacopoeia of Japan) and 0.025 ml of vaniline, 
followed by homogeneous suspending to obtain a suspension. 
[Effect of the Invention] 
(Test example) 
1. Evaluation of antitumor activity in vitro 
Antitumor activity was determined in vitro using a human cancer strain. As 
the culture medium for the cancer cell, an RPMI1640 solution containing 
10% of immobilized bovine fetal serum 50 .mu.g/ml of kanamycin was used. 
Cancer cells (1.times.10.sup.4 cells/ml) were innoculated to 1 ml of the 
culture liquids containing samples at different concentrations, 
respectively, and cultured in a carbon dioxide gas incubator at 37.degree. 
C. for 72 hours. 
Viability of the cancer cells was determined by MTT method in which the 
amount of living cells in the culture liquids containing the. sample and 
that in culture liquids containing no sample (blank group) are measured 
based on the intensity of the visible light using 
[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide] which 
develops color in proportion to the number of living cells. The intensity 
of antitumor activity was expressed by IC.sub.50 value (concentration 
(.mu.g/ml) necessary for inhibiting proliferation of the cells to 50%). 
The IC.sub.50 value was obtained from a graph illustrating the 
relationship between % proliferation of the cancer cells in the sample 
containing group (% relative to the blank group) and the concentration 
(logalithmic) of the sample. 
The results are summarized in Table 4. 
TABLE 4 
______________________________________ 
Antitumor activity in vitro 
IC.sub.50 (g/ml) 
Compound No. L1210 KB 
______________________________________ 
Example 9 0.21 15 
Example 12 3.1 7.6 
______________________________________ 
L1210: Mouse leukemia cell 
KB: human oral epidermoid carcinoma 
[Industrial utilizability] 
Compounds (1) and (2) of the present invention exhibit strong antitumor 
activities to P388 cell transplanted to a mouse and to various human 
cancers. They can be absorbed well by oral administration and have low 
toxicity with mild side effects. Accordingly, they are very useful for 
treatment or prophylaxis of tumorgenic diseases as novel pyrimidine 
nucleoside type antitumor agents. In addition, Compounds (1) and (2) of 
the present invention are very useful as intermediates for producing 
excellent antitumor agents. The pyrimidine nucleoside derivatives of the 
present invention can be administered to warm-blooded animals including 
human being. The administration form includes intravenous injections, 
subcutaneous injections, intramuscular injections and suppositories for 
parenteral administration, and tablets, capsules, powders and granules for 
oral administration. 
While the dose for adult varies depending on the disease to be treated, 
administration route, number of dosages and administration period, the 
preparation is administered in an amount of 0.01 to 5 g per day once or in 
several portions. 
Further, the present compounds can be used in combination with other 
antitumor agents such as nitrosourea drugs, e.g. 5Fu, AraC, ACNU and BCNU, 
cisplatin, daunomycin, adriamycin, mitomycin C or etoposide. In addition, 
the pyrimidine nucleoside derivative can be prepared into desired 
administration forms using arbitrarily conventional methods. The present 
invention therefore includes pharmaceutical preparations and compositions 
containing pharmaceutically acceptable pyrimidine nucleoside derivatives. 
The composition for injection is provided in unit dosage ampuls or 
multiple-dosage containers. The composition may contain additives such as 
suspending agents, stabilizers and dispersing agents, and usually is a 
powder which is redissolved before use in an appropriate solvent such as a 
sterilized aqueous medium containing no pyrogenic material. Such 
preparation can be prepared, for example, by dissolving a pyrimidine 
nucleoside derivative in acetone, pouring in vials and freeze-drying after 
addition of water. Further, the compositions for oral administration can 
be provided in the form of tablets, capsules, powders, granules and syrups 
containing suitable amounts of pyrimidine nucleoside derivatives for 
administration.