First glycoside synthesis via piperidinium salts of heterocyclic nitrogen bases: The synthesis of a new class of dihydropyridine thioglycosides

Article abstract of DOI:10.1081/CAR-120013502

A first reported method for preparation of a new class of thioglycosides via reaction of piperidinium salts of dihydropyridinethiones with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides has been studied. Comparison with the products obtai

Full text of DOI:10.1081/CAR-120013502

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
FIRST GLYCOSIDE SYNTHESIS VIA PIPERIDINIUM
SALTS OF HETEROCYCLIC NITROGEN BASES: THE
SYNTHESIS OF A NEW CLASS OF DIHYDROPYRIDINE
THIOGLYCOSIDES
Adel M. Attia & Galal H. Elgemeie
To cite this article: Adel M. Attia & Galal H. Elgemeie (2002) FIRST GLYCOSIDE SYNTHESIS VIA
PIPERIDINIUM SALTS OF HETEROCYCLIC NITROGEN BASES: THE SYNTHESIS OF A NEW CLASS
OF DIHYDROPYRIDINE THIOGLYCOSIDES, Journal of Carbohydrate Chemistry, 21:4, 325-339,
DOI: 10.1081/CAR-120013502
To link to this article: http://dx.doi.org/10.1081/CAR-120013502
Published online: 16 Aug 2006.
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JOURNAL OF CARBOHYDRATE CHEMISTRY
Vol. 21, No. 4, pp. 325–339, 2002
FIRST GLYCOSIDE SYNTHESIS VIA PIPERIDINIUM
SALTS OF HETEROCYCLIC NITROGEN BASES:
THE SYNTHESIS OF A NEW CLASS OF
DIHYDROPYRIDINE THIOGLYCOSIDES
*
Adel M. Attia and Galal H. Elgemeie
Department of Chemistry, Faculty of Science, Helwan University,
Ain-Helwan, Cairo, Egypt
ABSTRACT
A first reported method for preparation of a new class of thioglycosides via
reaction of piperidinium salts of dihydropyridinethiones with 2,3,4,6-tetra-O-
acetyl-a-D-gluco- and galactopyranosyl bromides has been studied. Compar-
ison with the products obtained from silylated thiopyridines is made.
INTRODUCTION
There is an increasing interest in the synthesis of nucleoside analogues and their
incorporation into DNA sequences for the study of ligand–DNA and protein–DNA
interactions. In recent reports from our laboratory, we described the preparation of
different novel functionalized pyridinethione glycosides, which revealed antagonistic
activity against human carcinoma cells and HIV-virus.[1–4] In an earlier brief com-
munication we had reported the use of dihydropyridinethione glycosides as P-glyco-
protein (Pgp) substrates or inhibitors in the protein glycosylation process.[5] These
common features, encouraged us to develop a new straightforward route for the synthesis
of these compounds. In the present report, we describe the synthesis of dihydropyridine
*
Corresponding author.
325
DOI: 10.1081/CAR-120013502
0732-8303 (Print); 1532-2327 (Online)
www.dekker.com
Copyright D 2002 by Marcel Dekker, Inc.

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326
ATTIA AND ELGEMEIE
thioglycosides through reaction of piperidinium salts of dihydropyridinethiolates with
d-acetylated a-glycosyl halides. As far as we know this is the first coupling reaction of
this type to be reported for glycoside formation. Thus, it has been found that
arylmethylidenecyanothioacetamide 1 reacted with 1,3-diketones 2 in ethanol contain-
ing piperidine at 0°C to give the corresponding piperidinium salts of 1,4-
dihydropyridine-2-thiones 3 (Scheme 1). The structure of 3 was established on the
basis of their elemental analysis and spectral data. Compound 3 reacted with 2,3,4,6-
tetra-O-acetyl-a-D-gluco- and galactopyranosyl bromides in acetone at 0°C to give in a
high yield the corresponding S-glucosides 5a–f or S-galactosides 5g–l , respectively.
CN
O
O
Ar
S
+
R
CH 3
NH2
1
2
EtOH/piperidine
0 o
C
Ar
O
R
CN
acetone / 30 o
C
H3C
acetone / 0 o
C
AcO
R2
+
-
ACO
R2
O
N
N
H
S
O
AcO
H
H
1
R
OAc
1
R
Br
3
Br
AcO
AcO
4
4
Ar
O
O
R
Ar
CN
S
CN
S
H3C
H3C
EtOH /
air / 3 min
R
N
N
H
AcO
ACO
R2
R2
O
O
AcO
1 AcO
1
R
R
AcO
AcO
8a-l
5a-l
NH3 / CH3OH
0 oC
NH3 / CH3OH
Ar
Ar
Ar
O
O
O
CN
CN
S
CN
H3C
H3C
H3C
R
N
S
R
N
H
R
N
SH
HO
R2
HO
R2
AcO
R2
O
O
O
HO
HO
1
R
AcO
1
R
1
R
HO
9a-l
HO
6a-l
AcO
7
Scheme 1.

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NEW DIHYDROPYRIDINE THIOGLYCOSIDES
327
The structure of the reaction products 5a–l were established by their elemental
1
analyses and spectral data (MS, IR, UV, H NMR, 13C NMR). As an example, the
analytical data for 5a indicated a molecular formula C29H31ClN2SO10 (m/z =634/636).
1
The H NMR spectrum showed the anomeric proton as a doublet at d 5.68 ppm. The
coupling constant J1’,2’ =9.8 Hz indicated H-1’ to be trans-diaxial to H-2’. The other six
glucose protons resonated at 4.05–4.98 ppm and the four acetyl groups appeared as
singlets at d 1.86–2.11 ppm. The 13C NMR spectrum of 5a contained a signal at d 82.5
corresponding to the C-1’ atom and five signals appearing at d 60.7, 68.1, 71.8, 73.8
and 75.5 that were assigned to C-6’, C-4’, C-2’, C-3’ and C-5’, respectively. After
deprotection of compounds 5a–l with a saturated solution of ammonia in methanol
at 0°C (Scheme 1) the final glycosides 6a–l were obtained in almost quantitative
yields, the structures of which have been established on the basis of elemental analyses
and spectral data. Thus, the analytical data for 6a revealed a molecular formula
1
C21H23ClN2SO6 (m/z=466/468). The H NMR spectrum showed the anomeric proton
as a doublet at d 5.78 ppm (J1’,2’ = 9.8 Hz) indicating a b-D-configuration. The signals of
the other six glucose protons appeared as a multiplet at d= 3.21–3.98 ppm, while the
signals that disappear on rapid exchange with D2O and are observed at d 4.69–5.08
ppm were assigned as the four hydroxyl groups, the 13C NMR spectrum of 6a is
characterized by a signal at d=84.6 ppm corresponding to the C-1’ and five other
signals at d 61.2, 69.4, 72.7, 77.7 and 81.2 ppm that are assigned to C-6’, C-4’, C-2’, C-
3’ and C-5’, respectively. In another experiment, the piperidinium salts 3 reacted with
2,3,4,6-tetra-O-acetyl-a-D-gluco- and galactopyranosyl bromides in acetone at 30°C
(Scheme 1) to afford the corresponding aromatized pyridine thioglucosides 8a–f and
thiogalactosides 8g–l. Compounds 8 could also be prepared by heating dihydro
thioglycosides 5 in ethanol for 3 minutes, which underwent spontaneous auto-oxidation
to afford the aromatized thioglycosides 8. The structures of the reaction products 8a–l
were established and confirmed on the basis of their elemental analyses and spectral
1
data (MS, IR, UV, H NMR, 13C NMR). The formation of S-glycosides 8 and not the
corresponding N-glycosides 7 (Scheme 1) were proved using 13C NMR spectroscopy
which revealed the absence of the thione carbon at d 178 ppm and the appearance of a
signal at d 160 ppm corresponding to the C-2 carbon, whose chemical shift is the same
as that of the corresponding S-methyl derivative.[6,7] When glycosides 8 were treated
with methanolic ammonia at room temperature, the free glycoside derivatives 9a–l
were obtained, the structures of which were established on the basis of elemental
analysis and spectral data. Encouraged by these results, we decided to synthesize the
pyridine thioglycosides 8 using the silylation method and comparing the resulting
products for stereochemical considerations. Thus, in a simple experimental procedure
(Scheme 2) treatment of the piperidinium salts 3 with dilute hydrochloric acid at 30°C
converted it to the corresponding pyridine-2(1H)thiones 11. The latter compounds were
reacted with hexamethyldisilazane (HMDS) in the presence of ammonium sulfate to
give the corresponding 2-trimethylsilylthiopyridine 12, which was subsequently treated
with peracetylated sugars 13 in the presence of redistilled SnCl4 to afford the S-
glycosyl compounds 8. The latter were shown to be the same as those obtained from
the reaction of 3 with 4 by comparison of their melting points and spectral data. In
summary, we have achieved a novel synthesis of interesting nonclassical dihydropy-
ridine thioglycosides and their corresponding aromatized forms by the reaction of the
piperidinium salts of dihydropyridinethiones with d-acetylated a-glycosyl halides, the

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328
ATTIA AND ELGEMEIE
HCl / 30 oC
CH3I / 30 oC
3
Ar
O
R
Ar
O
R
CN
CH3I
CN
H3C
H3C
KOH/ CH2Cl2
N
H
S
N
SCH3
10
11
HMDS
(NH4)2SO4
Ac O
R2
O
AcO
1
R
Ar
O
R
OAc
CN
AcO
13
H3C
8a-l
SnCl4/ CH3CN
S-Si(CH3)3
N
12
5,8
a
b
c
Ar
R
R1
R2 6,9
Ar
4-ClC6H4
4-CH3OC6H4 CH3 OH
R
R1
CH3 OH
R2
H
4-ClC6H4
CH3 OAc
H
a
b
c
d
e
f
4-CH3OC6H4 CH3 OAc
H
H
2-furanyl
4-ClC6H4
CH3 OAc
C6H5 OAc
H
2- furanyl
4-ClC6H4
CH3 OH
C6H5 OH
H
d
e
H
H
4-CH3OC6H4 C6H5 OAc
H
4-CH3OC6H4 C6H5 OH
H
f
2- furanyl
4-ClC6H4
C6H5 OAc
H
2- furanyl
4-ClC6H4
C6H5 OH
H
g
h
i
CH3
H
H
H
H
H
H
OAc
OAc
OAc
OAc
OAc
OAc
g
h
i
CH3
H
H
H
H
H
H
OH
OH
OH
OH
OH
OH
4-CH3OC6H4 CH3
4-CH3OC6H4 CH3
2- furanyl
4-ClC6H4
CH3
2- furanyl
4-ClC6H4
CH3
j
C6H5
j
C6H5
k
l
4-CH3OC6H4 C6H5
2- furanyl C6H5
k
l
4-CH3OC6H4 C6H5
2- furanyl C6H5
Scheme 2.
nature of the products depending upon thermodynamic factors. These glycosides can be
utilized as excellent starting materials for the synthesis of other carbohydrate deriva-
tives and for further biological evaluation studies.
EXPERIMENTAL
Melting points are uncorrected. Aluminum-coated silica gel 60 F254 (Merck)
sheets were used for thin-layer chromatography. IR spectra were collected in the
transmission mode on a Pye Unicam Spectra-1000 spectrometer. 1H and 13C NMR

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NEW DIHYDROPYRIDINE THIOGLYCOSIDES
329
spectra were measured in (CD3)2SO using SiMe4 as internal reference on a Varian 400
MHz spectrometer. Mass spectra were recorded by EI on a Varian Mat 311A
spectrometer and FAB on a Kratos MS 50 spectrometer.
Compounds 10 and 11 were prepared following literature procedures.[8] Yields
for synthesized compounds 8a–l are reported according to method (A).
3-Cyano-2-(2’ ,3’ ,4’ ,6’ -tetra-O-acetyl-b-D-glycopyranosylthio)-1,4-dihydropyri-
dines (5).
General coupling procedures. A mixture of 1a–l (0.01 mol) and 2 (0.01 mol)
was dissolved in dry ethanol (5 mL), and then piperidine (0.01 mol) were added. The
reaction mixture was stirred at 0°C for one h and then left to stand to room temper-
ature. The solvent was removed at reduced pressure and the resulting piperidinium salt
of 1,4-dihydropyridine-2-thione (3) was dissolved in dry acetone (5 mL) and a solution
of 2,3,4,6-tetra-O-acetyl-a-D-gluco- or galactopyranosyl bromide (0.01 mol) in dry
acetone (20 mL) was then added at 0°C. The reaction mixture was stirred until the
reaction was judged complete by TLC, using chloroform:ether 4:1 (Rf, 0.68–0.72),
then concentrated under reduced pressure and the residue crystallized from chloro-
form–petroleum ether at 0°C to give pale yellow crystals.
5a. Yield 67%, mp 133°C, [a]D +22.8; IR (KBr) 2221 (CN), 1752 (CO) cm À 1
,
1H NMR [(CD3)2SO, 400 MHz]: d 1.86–2.11 (4s, 12H, 4CH3CO), 2.32 (s, 3H,
CH3CO), 2.30 (s, 3H, CH3), 4.05 (m, 2H, 2H-6’), 4.16 (m, 2H, H-5’ and pyridine H-
4), 4.55 (d, 1H, H-4’), 4.98 (m, 2H, H-3’ and H-2’), 5.68 (d, J1’–2’ 9.8 Hz, 1H, H-1’),
6.90 (d, 2H, Ar–H), 7.10 (d, 2H, Ar–H), 8.32 (bs, 1H, NH); 13C NMR [(CD3)2SO,
400 MHz]: d 18.0–20.2 (5 CH3CO), 28.7 (CH3), 60.7 (C6’), 68.1 (C4’), 71.8 (C2’),
73.8 (C3’), 75.5 (C5’), 82.5 (C1’), 94.0 (C4), 108.8 (C3), 115.0 (CN), 128.2–139.0
(Ar–C), 137.7 (C5), 142.2 (C6), 157.0 (C2), 168.3–171.0 (4CO of glucose), 195.8
(CO of pyridine).
Anal. Calcd for C29H31ClN2SO10 (m/z 634): C, 54.84; H, 4.88; N, 4.41. Found:
C, 55.08; H, 5.02; N, 4.62%.
5b. Yield 68%, mp 178°C, [a]D +30.2; IR (KBr) 2206 (CN), 1758 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.92–2.03 (4s, 12H, 4CH3CO), 2.09 (s, 3H,
CH3CO), 2.32 (s, 3H, CH3), 3.86 (s, 3H, OCH3), 4.00 (m, 2H, 2H-6’), 4.18 (m, 2H, H-
5’ and pyridine H-4), 4.62 (d, 1H, H-4’), 4.96 (m, 2H, H-3’ and H-2’), 5.88 (d, J1’–2’ 9.6
Hz, 1H, H-1’), 6.92 (d, 2H, Ar–H), 7.15 (d, 2H, Ar–H), 8.22 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.9–20.3 (5CH3CO), 29.8 (CH3), 55.3 (OCH3), 61.9 (C6’),
68.1 (C4’), 70.3 (C2’), 72.8 (C3’), 75.0 (C5’), 83.5 (C1’), 94.5 (C4), 109.8 (C3), 114.4
(CN), 128.1–138.1 (Ar–C), 138.7 (C5), 144.2 (C6), 158.4 (C2), 169.2–170.0 (4CO of
glucose), 196.9 (CO of pyridine).
Anal. Calcd for C30H34N2SO11 (m/z 630): C, 57.14; H, 5.39; N, 4.44. Found: C,
57.36; H, 5.48; N, 4.60%.
1
5c. Yield 66%, mp 170°C, [a]D +32.7; IR (KBr) 2212(CN), 1755 (CO) cm À 1; H
NMR [(CD3)2SO, 400 MHz]: d 1.94–2.04 (4s, 12H, 4CH3CO), 2.22 (s, 3H, CH3CO),
2.30 (s, 3H, CH3), 4.03–4.22 (m, 3H, 2H-6’ and pyridine H-4), 4.93 (m, 2H, H-5’ and
H-4’), 5.39 (m, 2H, H-3’ and H-2’), 6.12 (d, J1’–2’ 9.6 Hz, 1H, H-1’), 6.81 (s, 1H, furan
H-4), 7.56 (dd, 1H, furan H-3), 8.05 (s, 1H, furan H-5), 8.88 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.8–20.1 (4CH3CO), 24.2 (CH3CO), 29.4 (CH3), 61.7 (C6’),

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ATTIA AND ELGEMEIE
67.6 (C4’), 72.5 (C2’), 74.9 (C3’), 82.3 (C5’), 83.6 (C1’), 89.6 (C4), 105.6 (C3), 118.1
(CN), 140.0–145.0 (furan–C), 145.4 (C5), 155.5 (C6), 162.2 (C2), 168.9–169.7 (4CO
of glucose), 196.1 (CO of pyridine).
Anal. Calcd for C27H30N2SO11 (m/z 590): C, 54.91; H, 5.08; N, 4.74. Found: C,
55.18; H, 5.20; N, 4.95%.
5d. Yield 66%, mp 128°C, [a]D +38.3; IR (KBr) 2210 (CN), 1748 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.90–2.10 (4s, 12H, 4CH3CO), 2.24 (s, 3H,
CH3CO), 4.03–4.29 (m, 3H, 2H-6’ and pyridine H-4), 5.05 (m, 2H, H-5’ and H-4’),
5.38 (m, 2H, H-3’ and H-2’), 6.18 (d, J1’–2’ 10.1 Hz, 1H, H-1’), 7.15–7.82 (m, 9H, Ar–
H), 8.65 (bs, 1H, NH).
Anal. Calcd for C34H33ClN2SO10 (m/z 696): C, 58.57; H, 4.73; N, 4.02. Found:
C, 58.76; H, 4.88; N, 4.32%.
5e. Yield 69%, mp 151°C, [a]D +42.5; IR (KBr) 2208 (CN), 1756 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.79–2.01 (4s, 12H, 4CH3CO), 2.06 (s, 3H,
CH3CO), 3.84 (s, 3H, OCH3), 4.02–4.19 (m, 4H, 2H-6’, H-5’ and pyridine H-4), 4.55
(d, 1H, H-4’), 4.99 (m, 2H, H-3’ and H-2’), 5.46 (d, J1’–2’ 10.2 Hz, 1H, H-1’), 6.88 (m,
2H, Ar–H), 7.14 (m, 2H, Ar–H), 7.48 (m, 5H, Ar–H), 8.42 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.2–20.4 (4CH3), 20.5 (CH3), 55.5 (OCH3), 61.9 (C6’), 67.7
(C4’), 69.5 (C2’), 72.9 (C3’), 74.9 (C5’), 83.5 (C1’), 92.6 (C4), 110.3 (C3), 114.8 (CN),
126.8–140.5 (Ar–C), 144.0 (C5), 158.4 (C6), 162.0 (C2), 169.2–169.9 (4CO of
glucose), 196.3 (CO of pyridine).
Anal. Calcd for C35H36N2SO11 (m/z 692): C, 60.69; H, 5.20; N, 4.04. Found: C,
60.86; H, 5.38; N, 4.30%.
5f. Yield 67%, mp 180°C, [a]D + 45.3; IR (KBr) 2208 (CN), 1755 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.82–2.02 (4s, 12H, 4CH3CO), 2.08 (s, 3H,
CH3CO), 4.03–4.19 (m, 3H, 2H-6’ and pyridine H-4), 4.70 (s, 1H, H-5’), 5.06 (m, 2H,
H-4’ and H-3’), 5.21 (t, 1H, H-2’), 6.08 (d, J1’–2’ 10.6 Hz, 1H, H-1’), 6.81 (q, 1H, furan
H-4), 7.62 (m, 6H, Ar–H and furan H-3), 8.05 (d, 1H, furan H-5), 8.95 (bs, 1H, NH);
13C NMR [(CD3)2SO, 400 MHz]: d 17.9–20.0 (4CH3), 24.1 (CH3), 61.6 (C6’), 68.1
(C4’), 69.3 (C2’), 73.1 (C3’), 74.9 (C5’), 82.5 (C1’), 95.5 (C4), 110.2 (C3), 115.1 (CN),
127.6–131.7 (Ar–C), 139.3–141.7 (furan–C), 154.9 (C5), 159.0 (C6), 162.1 (C2),
168.9–169.6 (4CO of glucose), 195.5 (CO of pyridine).
Anal. Calcd for C32H32N2SO11 (m/z 652): C, 58.89; H, 4.90; N, 4.29. Found: C,
59.14, H, 5.08; N, 4.52%.
1
5g. Yield 65%, mp 127°C, [a]D +21.6; IR (KBr) 2216 (CN), 1748(CO) cm À 1; H
NMR [(CD3)2SO, 400 MHz]: d 1.81–2.11 (4s, 12H, 4CH3CO), 2.40 (s, 3H, CH3CO),
2.33 (s, 3H, CH3), 4.00 (m, 2H, 2H-6’), 4.12 (m, 2H, H-5’ and pyridine H-4), 4.48
(d, 1H, H-4’), 4.77 (m, 2H, H-3’ and H-2’), 5.43 (d, J1’–2’ 9.7 Hz, H-1’), 6.95 (d, 2H,
Ar–H), 7.09 (d, 2H, Ar–H), 8.11 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d
18.11–21.0 (5 CH3CO), 28.0 (CH3), 60.0 (C6’), 68.0 (C4’), 71.4 (C2’), 73.3 (C3’), 75.0
(C5’), 81.9 (C1’), 94.7 (C4), 107.9 (C3), 116.0 (CN), 127.9–139.4 (Ar–C), 138.4 (C5),
140.9 (C6), 158.4 (C2), 168.0–172.0 (4CO of glucose), 196.0 (CO of pyridine).
Anal. Calcd for C29H31ClN2SO10 (m/z 634): C, 54.84; H, 4.88; N, 4.41. Found:
C, 55.09; H, 5.00; N, 4.63%.
1
5h. Yield 66%, mp 139°C, [a]D + 26.7; IR (KBr) 2212(CN), 1750(CO) cm À 1; H
NMR [(CD3)2SO, 400 MHz]: d 1.90–2.10 (4s, 12H, 4CH3CO), 2.34 (s, 3H, CH3CO),
2.39 (s, 3H, CH3), 3.99 (s, 3H, OCH3), 4.09 (m, 2H, 2H-6’), 4.22 (m, 2H, H-5’ and

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NEW DIHYDROPYRIDINE THIOGLYCOSIDES
331
pyridine H-4), 4.62 (d, 1H, H-4’), 4.89 (m, 2H, H-3’ and H-2’), 5.67 (d, J1’–2’ 9.7 Hz,
1H, H-1’), 6.99 (d, 2H, Ar–H), 7.19 (d, 2H, Ar–H), 8.10 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.0–20.0 (5CH3CO), 29.0 (CH3), 56.0 (OCH3), 61.8 (C6’),
68.0 (C4’), 71.0 (C2’), 72.6 (C3’), 74.9 (C5’), 82.9 (C1’), 95.7 (C4), 110.7 (C3), 115.6
(CN), 129.0–137.9 (Ar–C), 140.0 (C5), 145.0 (C6), 157.0 (C2), 167.0–172.6 (4CO of
glucose), 195.6 (CO of pyridine).
Anal. Calcd for C30H34SO11 (m/z 630): C, 57.14; H, 5.39; N, 4.44. Found: C,
57.38; H, 5.53; N, 4.62%.
5i. Yield 65%, mp 126°C, [a]D + 23.0; IR (KBr) 2205 (CN), 1754 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.96–2.08 (4s, 12H, 4CH3CO), 2.14 (s, 3H,
CH3CO), 2.22 (s, 3H, CH3), 4.08–4.42 (m, 2H, 2H-6’ and 1H, pyridine H-4), 4.86
(d, 1H, H-5’), 5.06 (m, 1H, H-4’), 5.36 (m, 2H, H-3’ and H-2’), 6.12 (d, J1’–2’ 10.0 Hz,
1H, H-1’), 6.52 (d, 1H, furan H-4), 7.58 (d, 1H, furan H-3), 8.02 (d, 1H, furan H-5),
9.25 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d 18.9–20.4 (CH3CO), 22.8
(CH3CO), 29.6 (CH3), 61.3 (C6’), 67.4(C4’), 70.7(C2’), 74.4 (C3’), 83.1 (C5’), 84.2
(C1’), 96.9 (C3), 110.4 (C4), 118.3 (CN), 140.6–146.7 (furan–C), 155.6 (C5), 157.7
(C6), 159.8 (C2), 169.1–169.8 (4CO of galactose), 196.2 (CO of pyridine).
Anal. Calcd for C27H39N2SO11 (m/z 590): C, 54.91; H, 5.08; N, 4.74. Found C,
55.13; H, 5.26; N, 5.04%.
5j. Yield 64%, mp 127°C, [a]D + 45.0; IR (KBr) 2202 (CN), 1753 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.78–2.10 (4s, 12H, 4CH3CO), 2.18 (s, 3H,
CH3CO), 4.02–4.38 (m, 3H, 2H-6’ and pyridine H-4), 4.68 (d, 1H, H-5’), 5.08 (m, 1H,
H-4’), 5.40 (m, 2H, H-3’ and H-2’), 5.82 (d, J1’–2’ 9.8 Hz, 1H, H-1’), 7.20–7.66 (m, 9H,
Ar–H), 8.47 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d 18.2–20.2 (4CH3CO),
20.9 (CH3CO), 61.2 (C6’), 67.5 (C4’), 70.7 (C2’), 73.9 (C3’), 74.3 (C5’), 83.9 (C1’),
91.6 (C4), 96.8 (C3), 118.4 (CN), 126.4–140.7 (Ar–C), 142.9 (C5), 158.2 (C6), 162.1
(C2), 169.2–169.8 (4CO of galactose), 196.0 (CO of pyridine).
Anal. Calcd for C34H33Cl N2SO10 (m/z 696): C, 58.57; H, 4.73; N, 4.02. Found:
C, 58.86; H, 4.82; N, 4.32%.
5k. Yield 67%, mp 143°C, [a]D + 36.4; IR (KBr) 2210 (CN), 1754(CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.74–2.08 (4s, 12H, 4CH3CO), 2.20 (s, 3H,
CH3CO), 3.85 (s, 3H, OCH3), 4.00–4.42 (m, 3H, 2H-6’ and pyridine H-4), 4.60 (d, 1H,
H-5’), 5.32 (m, 3H, H-4’, H-3’ and H-2’), 6.02 (d, J1’–2’ 9.6 Hz, 1H, H-1’), 6.92 (d, 2H,
Ar–H), 7.15 (d, 2H, Ar–H) 7.58 (m, 5H, Ar–H), 8.77 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.1–20.4 (4CH3CO), 25.3 (CH3CO), 55.2 (OCH3), 61.5
(C6’), 67.5 (C4’), 70.7 (C2’), 74.3 (C3’), 79.3 (C5’), 83.9 (C1’), 96.7 (C4), 110.4 (C3),
114.9 (CN), 126.4–140.0 (Ar–C), 145.2 (C5), 158.3 (C6), 165.3 (C2), 169.2–169.9 (4
CO of galactose), 196.2 (CO of pyridine).
Anal. Calcd for C35H36N2SO11 (m/z 692): C, 60.69 H, 5.20; N, 4.04. Found: C,
60.92; H, 5.38; N, 4.30%.
1
5l. Yield 65%, mp 135°C, [a]D + 36.5; IR (KBr) 2214 (CN) 1750 (CO) cm À 1; H
NMR [(CD3)2SO, 400 MHz]: d 1.88–2.04 (4s, 12H, 4CH3CO), 2.20 (s, 3H, CH3CO),
4.05–4.42 (m, 3H, 2H-6’ and pyridine H-4), 5.08 (m, 1H, H-5’), 5.38 (m, 3H, H-4’, H-
3’ and H-2’), 6.06 (d, J1’–2’ 10.1 Hz, 1H, H-1’), 6.35 (q, 1H, furan H-4), 7.52 (m, 6H,
Ar–H and furan H-3), 8.00 (d, 1H, furan H-5), 8. 80 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.1–20.4 (4CH3CO), 25.3 (CH3CO), 61.3 (C6’), 67.5 (C4’),
70.8 (C2’), 74.5 (C3’), 80.7 (C5’), 84.3 (C1’), 96.8 (C4), 110.5 (C3), 115.4 (CN),

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ATTIA AND ELGEMEIE
128.2–140.0 (Ar–C), 141.5–147.1 (furan–C), 155.2 (C5), 159.2 (C6), 162.2 (C2),
169.2–169.9 (4CO of galactose), 195.8 (CO of pyridine).
Anal. Calcd for C32H32N2SO11 (m/z 652): C, 58.89; H, 4.90; N, 4.29. Found: C,
58.97; H, 5.11; N, 4.45%.
3-Cyano-2-(b-D-glycopyranosylthio)-1,4-dihydropyridines (6).
General procedure for nucleoside deacylation. Dry gaseous ammonia was
passed through a solution of protected glycosides 5 (0.5 g) in 20 ml of dry methanol at
0°C for 0.5 h. The reaction mixture was stirred until completion as shown by TLC
(10–12 h), using chloroform:methanol, 9:1 (Rf 0.60–0.64). The resulting mixture was
then concentrated under reduced pressure to afford a solid residue that was crystallized
from methanol–ether at 0°C to furnish colourless crystals.
6a. Yield 80%, mp 168°C, [a]D +16.9; IR (KBr) 3660–3250 (OH), 2217 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.11 (s, 3H, CH3CO), 2.32 (s, 3H, CH3),
3.21–3.98 (m, 7H, 2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.69 (s, 1H, 2’-OH),
5.08 (m, 3H, 3’-OH, 4’-OH and 6’-OH), 5.78 (d, J1’–2’ 9.9 Hz, 1H, H-1’), 7.20 (d, 2H,
Ar–H), 7.42 (d, 2H, Ar–H), 8. 34 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d
19.4 (CH3CO), 30.1 (CH3), 61.2 (C6’), 69.4 (C4’), 72.7 (C2’), 77.7 (C3’), 81.2 (C5’),
84.6 (C1’), 89.4 (C4), 109.8 (C3), 118.8 (CN), 128.7–142.1 (Ar–C), 144.8 (C5), 145.0
(C6), 160.4 (C2), 196.6 (CO).
Anal. Calcd for C21H23ClN2SO6 (m/z 466): C, 54.01; H, 4.93; N, 6.00. Found: C,
54.34; H, 5.16; N, 6.22%.
6b. Yield 82%, mp 218°C, [a]D +21.0; IR (KBr) 3732–3209 (OH), 2229
1
(CN) cmÀ 1; H NMR [(CD3)2SO, 400 MHz]: d 2.13 (s, 3H, CH3CO), 2.34 (s, 3H,
CH3), 3.24–3.98 (m, 10H, 2H-6’, H-5’, H-4’, H-3’, H-2’, OCH3 and pyridine H-4),
4.46 (d, 1H, 2’-OH), 4.60 (s, 1H, 3’-OH), 5.04 (m, 2H, 4’-OH and 6’-OH), 5.63 (d,
J1’–2’ 9.9 Hz, 1H, H-1’), 7.13 (d, 2H, Ar–H), 7.64 (d, 2H, Ar–H), 8.66 (bs, 1H,
NH); 13C NMR [(CD3)2SO, 400 MHz]: d 19.0 (CH3CO), 24.5 (CH3), 55.4 (OCH3),
60.7 (C6’), 69.7 (C4’), 71.7 (C2’), 78.6 (C3’), 81.6 (C5’), 83.6 (C1’), 100.8 (C4),
110.5 (C3), 117.1 (CN), 127.4–132.0 (Ar–C), 152.9 (C5), 156.0 (C6), 161.8 (C2),
178.5 (CO).
Anal. Calcd for C22H26N2SO7 (m/z 462): C, 57.14; H, 5.62; N, 6.06. Found: C,
57.38; H, 5.81; N, 6.32%.
6c. Yield 81%, mp 203°C, [a]D +22.6; IR (KBr) 3680–3240 (OH), 2209 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.22 (s, 3H, CH3CO), 2.30 (s, 3H, CH3),
3.11–3.78 (m, 7H, 2H-6’, H-5’, H-4’, H-3’, H-2’ pyridine H-4), 4.67 (s, 1H, 2’-OH),
5.00 (m, 3H, 3’-OH, 4’-OH and 6’-OH), 5.55 (d, J1’–2’ 9.8 Hz, 1H, H-1’), 6.88 (q, 1H,
furan H-4), 7.38 (d, 1H, furan H-3), 8.00 (d, 1H, furan H-5), 8. 34 (bs, 1H, NH); 13C
NMR [(CD3)2SO, 400 MHz]: d 19.0 (CH3CO), 30.0 (CH3), 61.4 (C6’), 69.0 (C4’), 72.3
(C2’), 77.1 (C3’), 81.0 (C5’), 84.0 (C1’), 89.9 (C4), 109.0 (C3), 118.4 (CN), 128.3–
141.0 (furan–C), 144.0 (C5), 145.5 (C6), 160.0 (C2), 196.0 (CO).
Anal. Calcd for C19H22N2SO7 (m/z 422): C, 54.02; H, 5.21: N, 6.63. Found: C,
54.34; H, 5.46; N, 6.88%.
6d. Yield 80%, mp 188°C, [a]D +21.9; IR (KBr) 3630–3290 (OH), 2204 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.00 (s, 3H, CH3CO), 3.21–4.13 (m, 7H,
2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.44 (d, 1H, 2’-OH), 4.69 (m, 1H, 3’-

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OH), 4.78 (d, 1H, 4’-OH), 5.13 (d, 1H, 6’-OH), 5.56 (d, J1’–2’ 9.8 Hz, 1H, H-1’), 7.09–
7.78 (m, 9H, Ar–H), 8.13 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d 19.1
(CH3CO), 61.5 (C6’), 67.5 (C4’), 68.7 (C2’), 73.9 (C3’), 81.0 (C5’), 84.8 (C1’), 99.6
(C4), 108.9 (C3), 119.6 (CN), 126.9–130.7 (Ar–C), 143.9 (C5), 154.9 (C6), 160.6
(C2), 194.3 (CO).
Anal. Calcd for C26H25ClN2SO6 (m/z 528): C, 59.03; H, 4.73; N, 5.29. Found: C,
59.35; H, 4.92; N, 5.46%.
6e. Yield 78%, mp 181°C, [a]D +25.5; IR (KBr) 3690–3340 (OH), 2204 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.78 (s, 3H, CH3CO), 3.28–4.00 (m, 10H,
2H-6’, H-5’, H-4’, H-3’, H-2’, OCH3 and pyridine H-4), 4.70 (d, 1H, 2’-OH), 5.02 (m,
3H, 3’-OH, 4’-OH and 6’-OH), 5.96 (d, J1’–2’ 9.8 Hz, 1H, H-1’), 6.85 (d, 2H, Ar–H),
7.08 (d, 2H, Ar–H), 7.48 (m, 5H, Ar–H), 8.56 (bs, 1H, NH); 13C NMR [(CD3)2SO,
400 MHz]: d 18.4 (CH3CO), 55.1 (OCH3), 60.6 (C6’), 69.8 (C4’), 72.8 (C2’), 77.7
(C3’), 81.5 (C5’), 83.6 (C1’), 94.9 (C4), 110.5 (C3), 114.6 (CN,) 127.8–136.4 (Ar–C),
152.8 (C5), 158.2 (C6), 161.7 (C2), 196.2 (CO).
Anal. Calcd for C27H28N2SO7 (m/z 524): C, 61.83; H, 5.34; N, 5.34. Found: C,
62.09; H, 5.50; N, 5.58%.
6f. Yield 80%, mp 211°C, [a]D +28.4; IR (KBr) 3680–3210 (OH), 2214 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.96 (s, 3H, CH3CO), 3.18–3.78 (m, 7H,
2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.51–5.39 (m, 4H, 2’-OH, 3’-OH, 4’-
OH and 6’-OH), 6.12 (d, J1’–2’ 8.7 Hz, 1H, H-1’), 9.28 (d, 1H, furan H-4), 7.59–7.88
(m, 6H, Ar–H and furan H-3), 8.13 (d, 1H, furan H-5), 8.45 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 17.9 (CH3CO), 61.0 (C6’), 69.0 (C4’), 69.9 (C2’), 73.8 (C3’),
81.0 (C5’), 82.8 (C1’), 94.9 (C4), 111.4 (C3), 117.5 (CN), 126.0–138.6 (Ar–C), 140.6–
148.0 (furan–C), 151.7 (C5), 154.7 (C6), 161.6 (C2), 196.4 (CO).
Anal. Calcd for C24H24N2SO7 (m/z 484): C, 59.50; H, 4.95; N, 5.78. Found: C,
59.82; H, 5.13; N, 6.04%.
6g. Yield 78%, mp 192°C, [a]D +36.4; IR (KBr) 3650–3200 (OH), 2207 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.23 (s, 3H, CH3CO), 2.40 (s, 3H, CH3),
3.18–3.77 (m, 7H, 2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.72 (s, 1H, 2’-OH),
5.16 (m, 3H, 3’-OH, 4’-OH and 6’-OH), 5.65 (d, J1’–2’ 9.6 Hz, 1H, H-1’), 7.17 (d, 2H,
Ar–H), 7.34 (d, 2H, Ar–H), 8.23 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d
18.0 (CH3CO), 31.5 (CH3), 60.5 (C6’), 68.1 (C4’), 71.6 (C2’), 78.3 (C3’), 80.5 (C5’),
83.9 (C1’), 88.9 (C4), 108.3 (C3), 119.2 (CN), 127.9–142.0 (Ar–C), 143.6 (C5), 145.9
(C6), 162.5 (C2), 197.4 (CO).
Anal. Calcd for C21H23ClN2SO6 (m/z 466): C, 54.01; H, 4.93; N, 6.00. Found: C,
54.33; H, 5.14; N, 6.28%.
6h. Yield 78%, mp 177°C, [a]D +45.8; IR (KBr) 3710–3270 (OH), 2216( CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.94 (s, 3H, CH3CO), 2.30 (s, 3H, CH3),
3.22–4.02 (m, 10H, 2H-6’, H-5’, H-4’, H-3’, H-2’, OCH3 and pyridine H-4), 4.66 (m,
2H, 2’-OH and 3’-OH), 4.98 (m, 1H, 4’-OH), 5.34 (d, 1H, 6’-OH), 5.58 (d, J1’–2’ 9.6 Hz,
1H, H-1’), 7.16 (d, 2H, Ar–H), 7.38 (d, 2H, Ar–H), 8.77 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 19.1 (CH3CO), 23.1 (CH3), 55.2 (OCH3), 60.2 (C6’), 68.3
(C4’), 69.8 (C2’), 74.8 (C3’), 79.7 (C5’), 83.9 (C1’), 89.4 (C4), 102.4 (C3), 114.3 (CN),
127.9–138.0 (Ar–C), 156.1 (C5), 158.4 (C6), 160.5 (C2), 204.0 (CO).
Anal. Calcd for C22H26N2SO7 (m/z 462): C, 57.14; H, 5.62; N, 6.06. Found: C,
57.36; H, 5.78; N, 6.29%.

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ATTIA AND ELGEMEIE
6i. Yield 77%, mp 158°C, [a]D +50.2; IR (KBr) 3670–3180 (OH), 2210 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.19 (s, 3H, CH3CO), 2.35 (s, 3H, CH3),
3.09–3.85 (m, 7H, 2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.76 (s, 1H, 2’-OH),
5.12 (m, 3H, 3’-OH, 4’-OH and 6’-OH), 5.43 (d, J1’–2’ 9.7 Hz, 1H, H-1’), 6.45 (q, 1H,
furan H-4), 7.21 (d, 1H, furan H-3), 8.13 (d, 1H, furan H-5), 8. 25 (bs, 1H, NH); 13C
NMR [(CD3)2SO, 400 MHz]: d 18.9 (CH3CO), 31.4 (CH3), 62.2 (C6’), 68.7 (C4’), 71.7
(C2’), 78.0 (C3’), 80.6 (C5’), 83.7 (C1’), 88.6 (C4), 108.9 (C3), 119.0 (CN), 127.5–
140.8 (furan–C), 145.3 (C5), 146.0 (C6), 161.4 (C2), 195.7 (CO).
Anal. Calcd for C19H22N2SO7 (m/z 422): C, 54.02; H, 5.21; N, 6.63. Found: C,
54.36; H, 5.34; N, 6.88%.
6j. Yield 78%, mp 169°C, [a]D +45.7; IR (KBr) 3690–3270 (OH), 2206 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.78 (s, 3H, CH3CO), 3.26–4.04 (m, 7H,
2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.68 (d, 1H, 2’-OH), 4.76 (m, 1H,
3’-OH), 4.90 (d, 1H, 4’-OH), 5.08 (d, 1H, 6’-OH), 5.76 (d, J1’–2’ 9.4 Hz, 1H, H-1’),
7.22–7.74 (m, 9H, Ar–H), 8.55 (bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d 18.7
(CH3CO), 60.5 (C6’), 68.4 (C4’), 69.9 (C2’), 74.3 (C3’), 80.1 (C5’), 85.5 (C1’), 98.8
(C4), 109.8 (C3), 118.8 (CN), 127.8–131.9 (Ar–C), 144.7 (C5), 155.6 (C6), 161.8
(C2), 195.9 (CO).
Anal. Calcd for C26H25ClN2SO6 (m/z 528): C, 59.03; H, 4.73; N, 5.29. Found: C,
59.28; H, 4.95; N, 5.50%.
6k. Yield 81%, mp 208°C, [a]D +34.5; IR (KBr) 3690–2930 (OH), 2201 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.80 (s, 3H, CH3CO), 3.25–3.98 (m, 10H,
2H-6’, H-5’, H-4’, H-3’, H-2’, OCH3 and pyridine H-4), 4.40–5.22 (m, 4H , 2’-OH, 3’-
OH, 4’-OH and 6’-OH), 5.80 (d, J1’–2’ 9.6 Hz, 1H, H-1’), 6.94–7.98 (m, 9H, Ar–H), 8.89
(bs, 1H, NH); 13C NMR [(CD3)2SO, 400 MHz]: d 18.7 (CH3CO), 55.1 (OCH3), 60.6
(C6’), 68.5 (C4’), 70.0 (C2’), 74.4 (C3’), 80.2 (C5’), 85.5 (C1’), 90.7 (C4), 114.1 (C3);
119.2 (CN), 128.0–140.5 (Ar–C), 154.6 (C5), 158.4 (C6), 161.9 (C2), 196.5 (CO).
Anal. Calcd for C27H28N2SO7 (m/z 524): C, 61.83; H, 5.34; N, 5.34. Found: C,
62.14; H, 5.60; N, 5.64%.
6l. Yield 80%, mp 206°C, [a]D +33.9; IR (KBr) 3600–3220 (OH), 2208 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.82 (s, 3H, CH3CO), 3.22–3.96 (m, 7H,
2H-6’, H-5’, H-4’, H-3’, H-2’ and pyridine H-4), 4.68–5.44 (m, 4H, 2’-OH, 3’-OH, 4’-
OH and 6’-OH), 6.08 (d, J1’–2’ 8.7 Hz, 1H, H-1’), 9.36 (d, 1H, furan H-4), 7.68 (m, 6H,
Ar–H and furan H-3), 8.08 (d, 1H, furan H-5), 8.37 (bs, 1H, NH); 13C NMR
[(CD3)2SO, 400 MHz]: d 18.4 (CH3CO), 60.4 (C6’), 68.3 (C4’), 69.8 (C2’), 74.2 (C3’),
80.1 (C5’), 83.5 (C1’), 95.6 (C4), 110.4 (C3), 118.8 (CN), 127.8–139.9 (Ar–C), 141.8–
147.2 (furan–C), 152.8 (C5), 155.4 (C6), 162.0 (C2), 195.8 (CO).
Anal. Calcd for C24H24N2SO7 (m/z 484): C, 59.50; H, 4.95; N, 5.78. Found: C,
59.82; H, 5.16; N, 6.08%.
3-Cyano-2-(2’ ,3’ ,4’ ,6’ -tetra-O-acetyl-b-D-glycopyranosylthio)-pyridines (8).
General coupling procedures.
Method (A). The piperidinium salt of dihydropyridinethiones 3 (0.01 mol) was
dissolved in dry acetone (5 mL) and a solution of 2,3,4,6-tetra-O-acetyl-a-D-gluco- or
galactopyranosyl bromide (0.01 mol) in dry acetone (20 mL) was then added at 30°C.
The reaction mixture was stirred until the reaction was judged complete by TLC, using

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chloroform: petroleum ether 9:1 (Rf, 0.62–0.66), then concentrated under reduced
pressure at 40°C. The resulting product was crystallized from ethanol to afford pale
yellow crystals.
Method (B). A mixture of pyridine-2(1H)-thiones 11 (0.01 mol), hexamethyl-
disilazane (25 mL) and ammonium sulphate (0.02 g) were boiled under reflux, with
stirring for 48 h. The excess of hexamethyldisilazane was removed under diminished
pressure, providing the silylated bases 12 as a colorless oil. The latter was added to
a solution of 1,2,3,4,6-penta-O-acetyl-a-D-gluco- or galactopyranose (0.011 mol) in
dry acetonitrile (20 mL) and SnCl4 (1.6 mL). The reaction mixture was stirred at
room temperature for (6 h), poured into saturated NaHCO3 solution and then
extracted with CHCl3. The organic layers were dried over MgSO4, filtered and then
concentrated to give the crude nucleosides which were purified by recrystallization
from ethanol.
Method (C). A suspension of pyridine thioglycosides 5 (0.01 mol) in ethanol
were refluxed with stirring for 3 min. The resulting products were collected by
filtration and crystallized from ethanol.
8a. Yield 68%, mp 139°C, [a]D +26.4; IR (KBr) 2218 (CN), 1748 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.88–2.10 (5s, 15H, 5CH3CO), 2.35 (s, 3H, CH3),
4.09 (m, 3H, 2H-6’ and H-5’), 5.00 (t, 1H, H-4’), 5.16 (t, 1H, H-3’), 5.49 (t, 1H, H-2’),
6.11 (d, J1’–2’ 9.0 Hz, 1H, H-1’), 7.09 (d, 2H, Ar–H), 7.44 (d, 2H, Ar–H); 13C NMR
[(CD3)2SO, 400 MHz]: d 21.0–21.9 (4CH3CO), 23.0 (CH3CO), 30.0 (CH3), 60.9 (C6’),
67.1 (C4’), 67.6 (C2’), 74.0 (C3’), 75.7 (C5’), 81.2 (C1’), 107.6 (C3), 114.0 (CN),
126.9–134.0 (Ar–C), 152.0 (C4), 156.0 (C5), 159.3 (C6), 163.0 (C2), 166.0–168.2
(4CO of glucose), 200.0 (CO of pyridine).
Anal. Calcd for C29H29ClN2SO10 (m/z 632): C, 55.01; H, 4.58; N, 4.42. Found:
C, 55.42; H, 4.80; N, 4.73%.
8b. Yield 70%, mp 143°C, [a]D +33.6; IR (KBr) 2222 (CN), 1754 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.94–2.04 (5s, 15H, 5CH3CO), 2.58 (s, 3H, CH3),
3.88 (s, 3H, OCH3), 4.16 (m, 3H, 2H-6’ and H-5’), 5.04 (t, 1H, H-4’), 5.18 (t, 1H, H-3’),
5.56 (t, 1H, H-2’), 6.18 (d, J1’–2’ 10.5 Hz, 1H, H-1’), 7.12 (d, 2H, Ar–H), 7.34 (d, 2H,
Ar–H); 13C NMR [(CD3)2SO, 400 MHz]: d 20.2–20.3(4CH3CO), 22.9 (CH3CO), 31.2
(CH3), 55.3 (OCH3), 61.7 (C6’), 68.1 (C4’), 68.8 (C2’), 73.1 (C3’), 75.0 (C5’), 80.1
(C1’), 105.0 (C3), 114.4 (CN), 125.5–133.5 (Ar–C), 150.2 (C4), 157.2 (C5), 158.0
(C6), 160.6 (C2), 169.1–169.8 (4CO of glucose), 202.8 (CO of pyridine).
Anal. Calcd for C30H32N2SO11 (m/z 628): C, 57.32; H, 5.09; N, 4.45. Found: C,
57.66; H, 5.28; N, 4.73%.
8c. Yield 66%, mp 129°C, [a]D +30.0; IR (KBr) 2210 (CN), 1752 (CO) cm À 1
1H NMR [(CD3)2SO, 400 MHz]: d 1.90–2.12 (5s, 15H, 5CH3CO), 2.38 (s, 3H, CH3),
4.14 (m, 3H, 2H-6’ and H-5’), 5.20 (m, 2H, H-4’, H-3’), 5.68 (d, 1H, H-2’), 6.15 (d, J1’–2’
10.6 Hz, 1H, H-1’), 6.94 (m, 1H, furan H-4), 7.34 (d, 1H, furan H-3), 8.08 (d, 1H,
furan H-5).
Anal. Calcd for C27H28N2SO11 (m/z 588): C, 55.10; H, 4.76; N, 4.76. Found: C,
55.37; H, 4.92; N, 5.05%.
1
8d. Yield 68%, mp 161°C, [a]D +20.6; IR(KBr) 2215(CN), 1752 (CO) cm À 1; H
NMR [(CD3)2SO, 400 MHz]: d 1.88–2.12 (5s, 15H, 5CH3CO), 4.14 (m, 3H, 2H-6’ and
H-5’), 5.18 (m, 2H, H-4’ and H-3’), 5.62 (t, 1H, H-2’), 6.20 (d, J1’–2’ 10.1 Hz, 1H, H-1’),
7.66 (m, 9H, Ar–H).

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Anal. Calcd for C34H31Cl N2SO10 (m/z 494): C, 58.74; H, 4.46; N, 4.03. Found:
C, 59.12; H, 4.60; N, 4.35%.
8e. Yield 70%, mp 171°C, [a]D + 40.5; IR (KBr) 2218 (CN) 1748 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.94–2.08 (4s, 12H, 4CH3CO), 2.28 (s, 3H,
CH3CO), 3.82 (s, 3H, OCH3), 4.20 (m, 3H, 2H-6’ and H-5’), 5.08 (t, 1H, H-4’), 5.26
(t, 1H, H-3’), 5.64 (t, 1H, H-2’), 6.26 (d, J1’–2’ 10.8 Hz, 1H, H-1’), 6.85 (d, 2H, Ar–H),
7.18 (d, 2H, Ar–H), 7.62 (m, 5H, Ar–H); 13C NMR [(CD3)2SO, 400 MHz]: d 17.7–
20.3 (4 CH3CO), 23.0 (CH3CO), 55.0 (OCH3), 61.8 (C6’), 68.1 (C4’), 68.7 (C2’), 73.0
(C3’), 75.0 (C5’), 80.1 (C1’), 105.58 (C3), 114.6 (CN), 124.2–136.3 (Ar–C), 151.1
(C4), 154.4 (C5), 158.5 (C6), 160.1 (C2), 169.2–169.8 (4 CO of glucose), 195.0 (CO
of pyridine).
Anal. Calcd for C35H34N2SO11 (m/z 690): C, 60.86; H, 4.92; N, 4.05. Found: C,
61.12; H, 5.08; N, 4.34%.
8f. Yield 67%, mp 139°C, [a]D + 29.9; IR (KBr) 2208 (CN), 1755 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.99–2.15 (5s, 15H, 5CH3CO), 2.45 (s, 3H, CH3),
4.11 (m, 3H, 2H-6’ and H-5’), 5.12 (t, 1H, H-4’), 5.24 (t, 1H, H-3’), 5.50 (t, 1H, H-2’),
6.09 (d, J1’–2’ 9.5 Hz, 1H, H-1’), 7.00–7.99 (m, 8H, Ar–H and furan–H,); 13C NMR
[(CD3)2SO, 400 MHz]: d 22.0–22.9(4CH3CO), 24.5 (CH3CO), 32.0 (CH3), 61.9 (C6’),
67.9 (C4’), 67.9 (C2’), 74.5 (C3’), 75.9 (C5’), 81.9 (C1’), 108.6 (C3), 115.5 (CN),
127.0–136.6 (Ar–C and furan–C), 150.9 (C4), 155.6 (C5), 158.0 (C6), 165.8 (C2),
169.0–172.2 (4CO of glucose), 203.0 (CO of pyridine).
Anal. Calcd for C32H30N2SO11 (m/z 650): C, 59.07, H, 4.61; N, 4.30. Found: C,
59.38; H, 4.86; N, 4.58%.
8g. Yield 69%, mp 156°C, [a]D + 25.9; IR (KBr) 2204 (CN), 1752 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.90–2.16 (5s, 15H, 5CH3CO), 2.60 (s, 3H, CH3),
4.12 (m, 3H, 2H-6’ and H-5’), 5.20 (m, 1H, H-4’), 5.52 (m, 2H, H-3’ and H-2’), 5.98
(d, J1’–2’ 10.1 Hz, 1H, H-1’), 7.44 (m, 4H, Ar–H).
Anal. Calcd for C29H29ClN2SO10 (m/z 632): C, 55.01; H, 4.58; N, 4.42. Found:
C, 55.40; H, 4.73; N, 4.68%.
8h. Yield 71%, mp 167°C, [a]D +38.9; IR (KBr) 2220 (CN), 1752 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.94–2.05 (5s, 15H, 5CH3CO), 2.37 (s, 3H, CH3),
36.84 (s, 3H, OCH3), 4.15 (m, 3H, 2H-6’ and H-5’), 5.04 (t, 1H, H-4’), 5.22 (t, 1H, H-
3’), 5.55 (t, 1H, H-2’), 6.18 (d, J1’–2’ 10.5 Hz, 1H, H-1’), 7.12 (d, 2H, Ar–H), 7.34 (d,
2H, Ar–H); 13C NMR [(CD3)2SO, 400 MHz]: d 17.5–20.3 (4CH3CO), 22.9 (CH3CO),
31.2 (CH3), 55.3 (OCH3), 61.7 (C6’), 68.1 (C4’), 68.8 (C2’), 73.1 (C3’), 74.9 (C5’), 80.1
(C1’), 105.0 (C3), 114.3 (CN), 125.4–133.5 (Ar–C), 150.8 (C4), 153.4 (C5), 158.0
(C6), 160.8 (C2), 169.1–169.8 (4CO of galactose), 200.3 (CO of pyridine).
Anal. Calcd for C30H32N2SO11 (m/z 628): C, 57.32; H, 5.09; N, 4.45. Found: C,
57.68; H, 5.25; N, 4.72%.
8i. Yield 68%, mp 141°C, [a]D +27.5; IR (KBr) 2220 (CN), 1740 (CO) cm À 1; 1H
NMR [(CD3)2SO, 400 MHz]: d 1.83–2.11 (5s, 15H, 5CH3CO), 2.43 (s, 3H, CH3), 4.09
(m, 3H, 2H-6’ and H-5’), 5.02 (m, 2H, H-4’, H-3’), 5.55 (d, 1H, H-2’), 6.05 (d, J1’–2’ 10.0
Hz, 1H, H-1’), 6.90 (m, 1H, furan H-4), 7.11 (d, 1H, furan H-3), 8.00 (d, 1H, furan H-5).
Anal. Calcd for C27H28N2SO11 (m/z 588): C, 55.10; H, 4.76; N, 4.76. Found: C,
55.37; H, 4.98; N, 5.08%.
8j. Yield 70%, mp 196°C, [a]D + 31.4; IR (KBr) 2210 (CN), 1748 (CO) cm À 1
1H NMR [(CD3)2SO, 400 MHz]: d 1.96–2.18 (5s, 15H, 5CH3CO), 4.10 (m, 3H, 2H-6’
;

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337
and H-5’), 5.13 (m, 2H, H-4’ and H-3’), 5.40 (t, 1H, H-2’), 6.15 (d, J1’–2’ 9.7 Hz, 1H,
H-1’), 7.00–7.83 (m, 9H, Ar–H).
Anal. Calcd for C34H31ClN2SO10 (m/z 694): C, 58.74; H, 4.46; N, 4.03. Found:
C, 59.05; H, 4.62; N, 4.30%.
8k. Yield 65%, mp 121°C, [a]D +22.5; IR (KBr) 2214 (CN), 1755 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.88–2.14 (5s, 15H, 5CH3CO), 3.82 (s, 3H, OCH3),
4.15 (m, 3H, 2H-6’ and H-5’), 5.44 (m, 1H, H-4’), 5.72 (m, 2H, H-3’ and H-2’), 6.00
(d, J1’–2’ 10.3 Hz, 1H, H-1’), 6.96 (d, 2H, Ar–H), 7.12 (d, 2H, Ar–H), 7.48 (m, 5H,
Ar–H) ppm.
Anal. Calcd for C35H34N2SO11 (m/z 690): C, 60.86; H, 4.92; N, 4.05. Found: C,
61.20; H, 5.15; N, 4.34%.
8l. Yield 70%, mp 193°C, [a]D + 36.8; IR (KBr) 2210 (CN), 1754 (CO) cm À 1
;
1H NMR [(CD3)2SO, 400 MHz]: d 1.80–2.22 (5s, 15H, 5CH3CO), 2.50 (s, 3H, CH3),
4.05 (m, 3H, 2H-6’ and H-5’), 5.20 (t, 1H, H-4’), 5.40 (t, 1H, H-3’), 5.62 (t, 1H, H-2’),
6.16 (d, J1’–2’ 9.0 Hz, 1H, H-1’), 6.89–7.90 (m, 8H, Ar–H and furan–H); 13C NMR
[(CD3)2SO, 400 MHz]: d 20.3–21.7(4CH3CO), 26.0 (CH3CO), 60.2 (C6’), 68.0 (C4’),
67.5 (C2’), 75.3 (C3’), 77.4 (C5’), 80.7 (C1’), 111.0 (C3), 117.5 (CN), 124.0–138.0
(Ar–C and furan–C), 151.3 (C4), 154.6 (C5), 159.0 (C6), 166.2 (C2), 168.0–171.7
(4CO of glucose), 201.6 (CO of pyridine).
Anal. Calcd for C32H30N2SO11 (m/z 650): C, 59.07; H, 4.61; N, 4.30. Found: C,
59.41; H, 4.78; N, 4.62%.
3-Cyano-2-(b-D-glycopyranosylthio)-pyridines (9).
General procedure. Dry gaseous ammonia was passed through a solution of
protected nucleoside 8 (0.5 g) in dry methanol (20 mL) at room temperature for 10
min. The mixture was stirred until the reaction was judged complete by TLC (10–12 h)
using CHCl3:MeOH, 9:1 (Rf, 0.66–0.68). The resulting mixture was then concentrated
under reduced pressure to afford a solid residue that was crystallized from methanol to
give crystals.
9a. Yield 78%, mp 193°C, [a]D +22.6; IR (KBr) 3600–3180 (OH), 2206 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.05 (s, 3H, CH3CO), 2.36 (s, 3H, CH3),
3.20–3.84 (m, 6H, 2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.68 (m, 2H, 2’-OH and 3’-OH),
5.52 (m, 2H, 4’-OH and 6’-OH), 5.68 (d, J1’–2’ =10.0 Hz, 1H, H-1’), 7.42 (d, 2H, Ar–
H), 7.58 (d, 2H, Ar–H).
Anal. Calcd for C21H21ClN2SO6 (m/z 464): C, 54.25; H, 4.52; N, 6.02. Found: C,
54.62; H, 4.68; N, 6.29%.
9b. Yield 82%, mp 216°C, [a]D +31.8; IR (KBr) 3640–3210 (OH), 2211 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.09 (s, 3H, CH3CO), 2.36 (s, 3H, CH3),
3.19–3.65 (m, 6H, 2H-6’, H-5’, H-4’, H-3’ and H-2’), 3.99 (s, 3H, OCH3), 4.33 (d, 2H,
2’-OH and 3’-OH), 4.76 (d, 1H, 4’-OH), 5.22 (d, 1H, 6’-OH), 5.99 (d, J1’–2’ 10.0 Hz,
1H, H-1’), 7.00 (d, 2H, Ar–H), 7.36 (d, 2H, Ar–H).
Anal. Calcd for C22H24N2SO7 (m/z 460): C, 57.39; H, 5.21; N, 6.08. Found: C,
57.65; H, 5.32; N, 6.34%.
9c. Yield 81%, mp 215°C, [a]D +32.1; IR (KBr) 3610–3190 (OH), 2214 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.10 (s, 3H, CH3CO), 2.32 (s, 3H, CH3),
3.28–3.78 (m, 6H, 2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.60 (m, 2H, 2’-OH and 3’-OH),

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5.28 (m, 2H, 4’-OH and 6’-OH), 5.62 (d, J1’–2’ 10.0 Hz, 1H, H-1’), 6.92 (q, 1H, furan
H-4), 7.44 (d, 1H, furan H-3), 8.06 (d, 1H, furan H-5).
Anal. Calcd for C19H20N2SO7 (m/z 420): C, 54.28; H, 4.76; N, 6.66. Found: C,
54.46; H, 4.88; N, 6.92%.
9d. Yield 80%, mp 211°C, [a]D +45.0; IR (KBr) 3650–3220 (OH), 2215 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.13 (s, 3H, CH3CO), 3.18–3.82 (m, 6H,
2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.42(m, 2H, 2’-OH and 3’-OH), 5.58 (m, 2H, 4’-OH
and 6’-OH), 5.78 (d, J1’–2’ 9.9 Hz, 1H, H-1’), 7.55 (m, 9H, Ar–H).
Anal. Calcd for C26H23ClN2SO6 (m/z 526): C, 59.25; H, 4.36; N, 5.31. Found: C,
59.66; H, 4.49; N, 5.50%.
9e. Yield 79%, mp 207°C, [a]D +29.9; IR (KBr) 3680–3260 (OH), 2217 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.12 (s, 3H, CH3CO), 3.09–3.88 (m, 6H,
2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.04 (s, 3H, OCH3), 4.30 (d, 2H, 2’-OH and 3’-OH),
4.65 (d, 1H, 4’-OH), 5.17 (d, 1H, 6’-OH), 6.09 (d, J1’–2’ 10.7 Hz, 1H, H-1’), 7.10–7.86
(m, 9H, Ar–H).
Anal. Calcd for C27H26N2SO7 (m/z 522): C, 62.06; H, 4.98; N, 5.36. Found: C,
62.39; H, 5.17; N, 5.62%.
9f. Yield 79%, mp 205°C, [a]D 19.9; IR (KBr) 3640–3280 (OH), 2212 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.14 (s, 3H, CH3CO), 3.10–3.88 (m, 6H,
2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.23 (d, 2H, 2’-OH and 3’-OH), 5.00 (d, 1H, 4’-OH),
5.44 (d, 1H, 6’-OH), 5.67 (d, J1’–2’ 10.0 Hz, 1H, H-1’), 7.00–7.98 (m, 8H, Ar–H and
furan–H).
Anal. Calcd for C24H22N2SO7 (m/z 482): C, 59.75; H, 4.56; N, 5.80. Found: C,
60.12; H, 4.70; N, 6.05%.
9g. Yield 80%, mp 199°C, [a]D +48.8; IR (KBr) 3610–3230 (OH), 2216 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.02 (s, 3H, CH3CO), 2.34 (s, 3H, CH3),
3.16–3.80 (m, 6H, 2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.52 (d, 2H, 2’-OH and 3’-OH),
5.00 (d, 1H, 4’-OH), 5.42 (d, 1H, 6’-OH), 5.58 (d, J1’–2’ 10.4 Hz, 1H, H-1’), 7.40
(d, 2H, Ar–H), 7.68 (d, 2H, Ar–H).
Anal. Calcd for C21H21ClN2SO6 (m/z 464): C, 54.25; H, 4.52; N, 6.02. Found: C,
54.46; H, 4.70; N, 6.23%.
9h. Yield 81%, mp 217°C, [a]D +30.0; IR (KBr) 3620–3190 (OH), 2208 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.98 (s, 3H, CH3CO), 2.38 (s, 3H, CH3),
3.20–3.78 (m, 6H, 2H-6’, H-5’, H-4’, H-3’ and H-2’), 3.92 (s, 3H, OCH3), 4.55 (d, 2H,
2’-OH and 3’-OH), 4.98 (d, 1H, 4’-OH), 5.48 (d, 1H, 6’-OH), 5.70 (d, J1’–2’ 10.2 Hz,
1H, H-1’), 7.12 (d, 2H, Ar–H), 7.40 (d, 2H, Ar–H).
Anal. Calcd for C22H24N2SO7 (m/z 460): C, 57.39; H, 5.21; N, 6.08. Found: C,
57.70; H, 5.43; N, 6.39%.
9i. Yield 83%, mp 220°C, [a]D +28.9; IR (KBr) 3640–3250 (OH), 2213 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.12 (s, 3H, CH3CO), 2.40 (s, 3H, CH3),
3.12–3.74 (m, 6H, 2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.50 (d, 2H, 2’-OH and 3’-OH),
4.92 (d, 1H, 4’-OH), 5.44 (d, 1H, 6’-OH), 5.68 (d, J1’–2’ 10.3 Hz, 1H, H-1’), 6.84 (q,
1H, furan H-4), 7.36 (d, 1H, furan H-3), 8.00 (d, 1H, furan H-5).
Anal. Calcd for C19H20N2SO7 (m/z 420): C, 54.28; H, 4.76; N, 6.66. Found: C,
54.55; H, 4.98; N, 6.93%.
9j. Yield 81%, mp 206°C, [a]D 24.4; IR (KBr) 3680–3210 (OH), 2210 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 1.78 (s, 3H, CH3CO), 3.18–3.85 (m, 6H,

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2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.52 (d, 2H, 2’-OH and 3’-OH), 5.02 (d, 1H, 4’-OH),
5.48 (d, 1H, 6’-OH), 5.74 (d, J1’–2’ 10.2 Hz, 1H, H-1’), 7.58 (m, 9H, Ar–H).
Anal. Calcd for C26H23ClN2SO6 (m/z 526): C, 59.25; H, 4.36; N, 5.31. Found: C,
59.63; H, 4.52; N, 5.65%.
9k. Yield 80%, mp 202°C, [a]D +30.8; IR (KBr) 3680–3260 (OH), 2212 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.19 (s, 3H, CH3CO), 3.09–3.93 (m, 6H,
2H-6’, H-5’, H-4’, H-3’ and H-2’), 3.99 (s, 3H, OCH3), 4.34 (d, 2H, 2’-OH and 3’-OH),
5.00 (d, 1H, 4’-OH), 5.52 (d, 1H, 6’-OH), 5.99 (d, J1’–2’ 9.7Hz, 1H, H-1’), 7.13–7.90
(m, 9H, Ar–H).
Anal. Calcd for C27H26N2SO7 (m/z 522): C, 62.06; H, 4.98; N, 5.36. Found: C,
62.39; H, 5.22; N, 5.64%.
9l. Yield 81%, mp 207°C, [a]D +43.9; IR (KBr) 3640–3190 (OH), 2215 (CN)
1
cm À 1; H NMR [(CD3)2SO, 400 MHz]: d 2.00 (s, 3H, CH3CO), 3.19–3.97 (m, 6H,
2H-6’, H-5’, H-4’, H-3’ and H-2’), 4.54 (d, 2H, 2’-OH and 3’-OH), 5.28 (d, 1H, 4’-OH),
5.53 (d, 1H, 6’-OH), 5.99 (d, J1’–2’ 9.6 Hz, 1H, H-1’), 6.78–7.77 (m, 8H, Ar–H and
furan–H).
Anal. Calcd. for C24H22N2SO7 (m/z 482): C, 59.75; H, 4.56; N, 5.80. Found: C,
60.12; H, 4.80; N, 6.08%.
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Received December 30, 2001
Accepted April 23, 2002