A convenient method for the synthesis of 2-(β-D-glycopyranosylthio) pyridines

Article abstract of DOI:10.1081/NCN-120023269

Treatment of piperidinium salts of dihydropyridinethiolates 3 with glycosyl bromides 4 in dry acetone provides a convenient and high yielding synthesis of 1,4-dihydro-3-cyanopyridine thioglycosides 5. The structures of 5 were confirmed by oxidation as wel

Full text of DOI:10.1081/NCN-120023269

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A Convenient Method for the Synthesis of 2-(β-D-
Glycopyranosylthio) Pyridines
Adel M. E. Attia a b & Ashraf A. El-Shehawy a
a Department of Chemistry , Faculty of Education , University of Tanta (Kafr El-Sheikh
Branch) , Tanta, Egypt
b Department of Chemistry , Faculty of Education , University of Tanta (Kafr El-Sheikh
Branch) , Egypt
Published online: 07 Feb 2007.
To cite this article: Adel M. E. Attia & Ashraf A. El-Shehawy (2003) A Convenient Method for the Synthesis of 2-(β-D-
Glycopyranosylthio) Pyridines, Nucleosides, Nucleotides and Nucleic Acids, 22:9, 1737-1746, DOI: 10.1081/NCN-120023269
To link to this article: http://dx.doi.org/10.1081/NCN-120023269
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NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS
Vol. 22, No. 9, pp. 1737–1746, 2003
A Convenient Method for the Synthesis of
2-(b-D-Glycopyranosylthio) Pyridines
*
Adel M. E. Attia and Ashraf A. El-Shehawy
Department of Chemistry, Faculty of Education, University of Tanta
(Kafr El-Sheikh Branch), Tanta, Egypt
ABSTRACT
Treatment of piperidinium salts of dihydropyridinethiolates 3 with glycosyl
bromides 4 in dry acetone provides a convenient and high yielding synthesis of
1,4-dihydro-3-cyanopyridine thioglycosides 5. The structures of 5 were confirmed
1
by oxidation as well as by H NMR and 13C NMR spectral analysis.
Key Words: Piperidinium salts; Glycosyl bromides; Dihydropyridine thioglyco-
sides; Medicinal cavity.
The bioisosteric replacement of nitrogen by carbon in pyrimidine heterocycle
of the naturally occurring pyrimidine nucleosides cytidine and uridine has gener-
ated effective inhibitors of cell growth.[1,2] 3-Deazauridine and 3-deazacytidine pro-
duced significant growth inhibition against L-1210 leukemia cells in vitro[3] and
have also shown antiviral activity against RNA viruses.[4] The 3-deazapyrimidine
nucleosides, substituted analogously to naturally occurring pyrimidines, constitute
another logical class of analogous with potential biological activity.[5–7] As a part
of our program of research on the synthesis of new pyridine and pyrimidine
nucleosides[8–13] with considerable biological and medicinal activity, we report here
*Correspondence: Adel M. E. Attia, Department of Chemistry, Faculty of Education, Univer-
sity of Tanta (Kafr El-Sheikh Branch), Egypt; E-mail: adelmattia@hotmail.com.
1737
DOI: 10.1081/NCN-120023269
Copyright # 2003 by Marcel Dekker, Inc.
1525-7770 (Print); 1532-2335 (Online)
www.dekker.com

1738
Attia and El-Shehawy
a convenient method for the synthesis of a new class of non-natural nucleosides,
2-(b-D-glycopyranosylthio)-1,4-dihydropyridines. In addition, we have tested these
glycosides against HIV. Thus, 3-aryl-2-cyano(thioacrylamides) 1 have been found
to react with aliphatic ketones 2 in ethanol containing equivalent amounts of
piperidine at room temperature to give the corresponding piperidinium salts of
1,4-dihydropyridinethiones 3. Compounds 3 reacted with tetra-O-acetyl-a-D-gluco-
pyranosyl bromide or its a-D-galactopyranosyl isomer 4 in dry acetone at 0ꢀC to
give the corresponding dihydrothioglycosides 5 in high yields. The structures of the
reaction products 5 were established and confirmed by the correct analytical and
spectral data. The 1H NMR spectrum of 5b showed a doublet at d 6.10
(J ¼ 10.5 Hz) assigned to the anomeric proton of the glucose moiety with a diaxial
orientation of H-10 and H-20 indicating the presence of only b-configuration and
4C1 (D) conformation for this glucoside. Ammonolysis of protected glycosides 5
with methanolic ammonia at 0ꢀC furnished the free glycosides 2-(b-D-glycopyrano-
1
sylthio)-1,4-dihydro-3-cyanopyridines 7 in 85–88% yields. The H NMR spectrum
of 7g showed the anomeric proton as a doublet at d 5.60 (J ¼ 10.1 Hz) indicating
the presence of only the b-D-galactopyranoside. In another experiment, the dihy-
drothioglycosides 5a-h were heated at reflux in dry ethanol for three minutes,
the corresponding aromatized pyridine thioglycosides 10a-h were obtained. In
order to investigate the scope of the formation of these glycosides further we stu-
died the coupling of 3-aryl-2-cyano(thioacrylamide) potassium salts 8 with tetra-O-
acetyl-a-D-glycopyranosyl bromides 4 in aqueous acetone at room temperature to
give the corresponding 3-aryl-2-cyanoacrylamide thioglycosides 9. Compounds 9
reacted with aliphatic ketones 2 in dry ethanol containing catalytic amounts of
piperidine at 60ꢀC to afford the pyridine thioglycosides 10a-h.
Although the coupling of piperidinium salts 3 with the glycosyl bromides 4
could also give the corresponding N-glycosides 6, the formation S-glycosides 5
were proved using the 13C NMR spectroscopy which revealed the absence of a C-
2 thione carbon at d 162 of the same value of the corresponding S-methyl deriva-
tives.[13] Removal of the protecting acetyl groups from the glycon moiety of 10 with
ammonia in methanol at room temperature furnished 2-(b-D-glycopyranosylthio)
pyridiness 11.
In conclusion, we have synthesized dihydropyridine thioglycosides and their aro-
matized derivatives, via piperidinium salts. The high yields, high purity of products
and experimental simplicity make this method particular attractive. The glycosides
5a-h and 7a-h did not show any significant activity against Human Immunodefi-
ciency Virus HIV in MT-4 cells at a concentration of 100 mg=mL. None of the free
glycosides showed cytotoxicity at this concentration.
EXPERIMENTAL
Melting points are uncorrected. TLC was carried out on aluminum sheet silica
gel 60 F254 (Merck) detected by short UV light. IR Spectra were obtained (kBr) using
1
a Pye Unicam spectra 1000. H NMR and 13C NMR spectra were measured on a
Varian 400 MHz spectrometer in DMSO-d6 using SiMe4 as internal standard. Mass

Synthesis of 2-(b-D-Glycopyranosylthio) Pyridines
1739

1740
Attia and El-Shehawy
spectra were recorded by EI on a Varian Mat 311 A spectrometer and by FAB on a
Kratos MS spectrometer.
3-Cyano-2-(2,3,4,6-tetra-O-acetyl-b-D-glycopyranosylthio)-
1,4-dihydrophridines (5a-h)
General Coupling Procedures. To a mixture of 3-aryl-2-cyano(thioarylamides) 1
(0.01 mol) and 2 (0.01 mol) in dry ethanol (5 mL), was added piperidine (0.01 mol).
The reaction mixture was stirred at room temperature for one hour, then evaporated
under reduced pressure and the resulting piperidinium salt 3 was dissolved in dry
acetone (5 mL) and a solution of glycosyl bromide 4 (0.001 mol) in dry acetone
(20 mL) was then added to 0ꢀC. The mixture was stirred until the reaction was
judged complete by TLC (4–6 h), using chloroform-ether (9:1 v=v) (Rf 0.70–0.74
region), then evaporated under reduced pressure for 15 min. The residue was crystal-
lized from chloroform-petroleum ether 40–60 at 0ꢀC to give the title compounds 5.
5a. Yield 78%, mp 139ꢀC; IR 3390 (NH), 2218 (CN), 1748 (CO) CMꢁ1
;
1H NMR d 1.95-2.07 (4s, 12H, 4CH3CO), 2.40 (s, 3H, CH3), 3.88 (s, 3H OCH3),
4.13 (m, 2H, 2H-60), 4.28 (m, 2H, H-50 and0pyridine H-4), 5.03 (m, 3H, H-40, H-30
and H-20), 6.12 (d, J1 –2 ¼ 10.3 Hz, 1H, H-1 ), 7.60 (m, 4H, Ar-H and 1H, pyridine
H-5), 8.19 (s, 1H, NH); 13C NMR d 18.9 (CH3), 20.2–24.3 (4CH3CO), 55.3 (OCH3),
61.7 (C60), 67.8 (C40), 68.9 (C20), 73.2 (C30), 75.0 (C50), 80.3 (C10), 102.5 (C4), 110.6
(C3), 115.5 (CN), 125.0–142.9 (Ar-C), 152.9 (C5), 155.9 (C6), 162.1 (C2), 169.2–
170.0 (4COCH3); MS m=z 588; Anal. Calcd for C28H32N2SO10: C, 57.14; H, 5.44;
N, 4.76. Found: C, 57.30; H, 5.59; N, 4.91.
0
0
5b. Yield 80%, mp 144ꢀC; IR 3360 (NH), 2216 (CN), 1750 (CO) cmꢁ1
;
1H NMR d 1.94–2.02 (4s, 12H, 4CH3CO), 2.38 (s, 3H, CH3), 4.02 (m, 2H, 2H-60),
4.15 (m, 2H, H-50 and pyridine H-4), 5.02 (t, J ¼ 9.2 Hz, 1H, H-40), 5.17(t, J ¼ 8.9
0
Hz, 1H, H-30), 5.53 (t, J ¼ 9.1 Hz, 1H, H-20), 6.10 (d, J1 –2 ¼ 10.5 Hz, 1H, H-1 ),
6.83 (m, 1H, furan H-4), 7.07 (S, 1H, pyridine H-5), 7.60 (m, 1H furan H-3), 8.08
(dd, 1H furan H-5), 8.28 (s, br, 1H NH); 13C NMR d 19.0 (CH3), 20.2–24.4
(4CH3CO), 61.7 (C60), 68.1 (C40), 72.4 (C20), 73.1 (C30), 74.9 (C50), 80.2 (C10),
97.9 (C4), 113.0 (C3), 115.4 (CN), 119.9 (furan C4), 139.8 (furan C3), 146.0 (C5),
147.1 (C6), 152.9 (furan C5), 159.2 (furan C2), 162.2 (C2), 169.2–169.8 (4COCH3);
MS m=z 548; Anal. Calcd for C25H28N2SO10: C, 54.74; H, 5.11; N, 5.11. Found:
C, 55.05; H, 5.30; N, 5.38.
0
0
5c. Yield 76%, mp 126ꢀC; IR 3380 (NH), 2220 (CN), 1746 (CO) cmꢁ1
;
1H NMR d 1.35 (t, J ¼ 6.6 Hz, 3H, CH3), 1.96–2.07 (4s, 12H, 4CH3CO), 2.71 (q,
2H, CH2), 3.83 (s, 3H, OCH3), 4.05 (m, 2H, 2H-60), 4.20 (m, 2H, H-50 and pyridine
H-4), 5.09 (m, 2H, H-40 and H-30), 5.57 (t, J ¼ 9.3 Hz, 1H, H-20), 6.15 (d, J1 –2 ¼ 10.5
Hz, 1H, H-10), 7.38 (m, 4H, Ar-H and 1H, pyridine H-5), 8.30 (s, 1H, NH); 13C
NMR d 15.4 (CH3), 20.2–23.7 (4CH3CO), 24.8 (CH2), 55.0 (OCH3), 61.7 (C60),
68.1 (C40), 68.9 (C20), 73.2 (C30), 75.0 (C50), 80.3 (C10), 105.7 (C4), 113.6 (C3),
115.1 (CN), 124.9–142.8 (Ar-C), 153.0 (C5), 158.3 (C6), 162.0 (C2), 169.2–169.8
0
0

Synthesis of 2-(b-D-Glycopyranosylthio) Pyridines
1741
(4COCH3); MS m=z 602; Anal. Calcd for C29H34N2SO10: C, 57.81; H, 5.65; N, 4.65.
Found: C, 58.08; H, 5.79; N, 4.88.
1
5d. Yield 77%, mp 150ꢀC; IR 3330 (NH), 2213 (CN), 1755 (CO) cmꢁ1; H
NMR d 1.33 (t, J ¼ 7.0 Hz, 3H, CH3), 1.92–2.03 (4s, 12H, 4CH3CO), 2.88 (q, 2H,
CH2), 4.08 (m, 2H, 2H-60), 4.24 (m, 2H, H-50 and pyridine H-4), 5.16 (m, 2H, H-
0
40 and H-30), 5.56 (t, J ¼ 9.2 Hz, 1H, H-20), 6.12 (d, J1 –2 ¼ 10.5 Hz, 1H, H-1 ),
6.78 (m, 1H, furan H-4), 7.03 (s, 1H, pyridine H-5), 7.58 (m, 1H, furan H-3), 8.05
(dd, 1H, furan H-5), 8.24 (s, 1H, NH): 13C NMR d 15.8 (CH3), 20.2–23.8 (4CH3CO),
30.6 (CH2), 61.7 (C60), 67.2 (C40), 68.8 (C20), 73.0 (C30), 74.9 (C50), 80.3 (C10), 97.3
(C4), 112.9 (C3), 115.4 (CN), 127.0 (furan C4), 140.1 (furan C3), 145.8 (C5), 147.2
(C6), 154.9 (furan C5), 159.4 (furan C2), 162.4 (C2), 169.2–169.8 (4COCH3); MS
m=z 562; Anal. Calcd for C26H30N2SO10: C, 55.52; H, 5.34; N, 4.98. Found: C,
55.81; H, 5.47; N, 5.19.
0
0
5e. Yield 76%, mp 130ꢀC; IR 3320 (NH), 2214 (CN), 1751 (CO) cmꢁ1
;
1H NMR d 1.95–2.07 (4s, 12H, 4CH3CO), 2.34 (s, 3H, CH3), 3.84 (s, 3H, OCH3),
4.03 (m, 2H, 2H-60), 4.19 (m, 2H, H-50 and p0yridine H-4), 5.03 (m, 3H, H-40, H-30
and H-20), 6.08 (d, J1 –2 ¼ 10.5 Hz, 1H, H-1 ), 77.63 (m, 4H, Ar-H and pyridine
H-5), 8.18 (s, 1H, NH); 13C NMR d 18.2 (CH3), 20.3–27.4 (4CH3CO), 54.9
(OCH3), 61.3 (C60), 67.5 (C40), 70.8 (C20), 73.9 (C30), 74.5 (C50), 83.3 (C10), 105.7
(C4), 113.4 (C3), 116.9 (CN), 126.4–146.7 (Ar-C), 152.0 (C5), 155.1 (C6), 160.8
(C2), 169.2–169.8 (4 COCH3); MS m=z 588; Anal. Calcd for C28H32N2SO10: C,
57.14; H, 5.44; N, 4.76. Found: C, 57.40; H, 5.63; N, 4.99.
0
0
5f. Yield 79%, mp 149ꢀC; IR 3365 (NH), 2222 (CN), 1750 (CO) cmꢁ1; MS m=z
548; Anal. Calcd for C25H28N2SO10: C, 54.74; H, 5.11; N, 5.11. Found: C, 55.07;
H, 5.29; N, 5.35.
1
5g. Yield 75% mp 137ꢀC; IR 3340 (NH), 2210 (CN), 1754 (CO) cmꢁ1; H
NMR d 1.37 (t, J ¼ 6.6 Hz, 3H, CH3), 1.92–2.15 (4s, 12H 4CH3CO), 2.88 (q, 2H,
CH2), 3.85 (s, 3H, OCH3), 4.06 (m, 2H, 2H-60), 4.42 (m, 2H, H-50 and pyridine H-4),
0
5.41 (m, 3H, H-40, H-30 and H-20), 6.13 (d, J1 –2 ¼ 10.4 Hz, 1H, H-1 ), 7.48 (m, 4H,
Ar-H and 1H, pyridine H-5), 8.13 (s, 1H, NH); 13C NMR d 15.4 (CH3), 20.3–
23.7 (4CH3CO), 27.2 (CH2), 55.1 (OCH3), 61.3 (C60), 66.3 (C40), 67.6 (C20), 71.0
(C30), 74.1 (C50), 80.7 (C10), 105.7 (C4), 114.0 (C3), 115.1 (CN), 127.3–138.0 (Ar-
C), 152.3 (C5), 159.6 (C6), 161.7 (C2), 169.3–169.9 (4 COCH3); MS m=z 602; Anal.
Calcd for C29H34N2SO10: C, 57.81; H, 5.65; N, 4.65. Found: C, 58.20; H, 5.81;
N, 4.93.
0
0
1
5h. Yield 78% mp 167ꢀC; IR 3370 (NH), 2208 (CN), 1746 (CO) cmꢁ1; H
NMR d 1.34 (t, J ¼ 6.4 Hz, 3H, CH3), 1.93–2.16 (4s, 12H 4CH3CO), 2.90 (q, 2H,
CH2), 4.04 (m, 2H, 2H-60), 4.42 (m, 2H, H-50 and pyridine H-4), 5.26 (t, J ¼ 9.7 Hz,
0
1H, H-40), 5.52 (m, 2H, H-30 and H-20), 6.14 (d, J1 –2 ¼ 10.6 Hz, 1H, H-1 ),
6.76 (m, 1H, furan H-4), 7.12 (s, 1H, pyridine H-5), 7.59 (m, 1H, furan H-3), 8.01
(dd, 1H, furan H-5), 8.34 (s, 1H, NH); 13C NMR d 15.8 (CH3), 20.6–23.8 (4CH3CO),
30.7 (CH2), 61.5 (C60), 66.9 (C40), 67.6 (C20), 70.9 (C30), 74.1 (C50), 80.7 (C10), 103.5
0
0

1742
Attia and El-Shehawy
(C4), 113.0 (C3), 115.0 (CN), 123.4 (furan C4), 140.8 (furan C3), 146.1 (C5), 150.0
(C6), 154.9 (furan C5), 159.3 (furan C2), 162.6 (C2), 169.3–169.9 (4 COCH3); MS
m=z 562; Anal. Calcd for C26H30N2SO10: C, 55.52; H, 5.34; N, 4.98. Found: C,
55.77; H, 5.50; N, 5.29.
3-Cyano-2-(b-D-glycopyranosylthio)-1,4-dihydropyridines (7a-h)
General Procedure for Nucleoside Deacylation. Dry gaseous ammonia was
passed through a solution of acetylated glycosides 5 (0.5 gm) in dry methanol
(10 mL) at 0ꢀC for about 0.5 h. The reaction mixture was stirred at 0ꢀC until com-
plete as shown by TLC (10 to 12 h), using chloroform-methanol (19 : 1 v=v) (Rf
0.68–0.70 region). The resulting mixture was then concentrated under reduced
pressure to afford a solid residue that was crystallized from methanol-ether at 0ꢀC
to furnish the title compounds 7.
1
7a. Yield 87%, mp 189ꢀC; IR 3620–3180 (OH and NH), 2215 (CN) cmꢁ1; H
NMR d 2.39 (s, 3H, CH3), 3.24–3.98 (m, 6H, 2H-60, H-50-H-40, H-30, H-20 and 1H,
pyridine H-4), 4.52 (m, 2H, 20-OH and 30-OH), 5.08 (m, 2H, 40-OH and 60-OH), 5.68
0
0
0
(d, J1 –2 ¼ 9.9 Hz, 1H, H-1 ), 7.39 (m, 4H, Ar-H and 1H, pyridine H-5), 8.14 (s, 1H,
NH); MS m=z 420; Anal. Calcd for C20H24N2SO6: C, 57.14; H, 5.71; N, 6.67.
Found: C, 57.40; H, 5.89; N, 6.93.
1
7b. Yield 86%, mp 196ꢀC IR 3630–3200 (OH and NH), 2218 (CN) cmꢁ1; H
NMR d 2.39 (s, 3H, CH3), 3.36–3.96 (m, 6H, 2H-60, H-50-H-40, H-30, H-20 and
1H, pyridine H-4), 4.60 (m, 2H, 20-OH and 30-OH), 5.18 (m, 2H, 40-OH and 60-
0
0
0
OH), 5.70 (d, J1 –2 ¼ 9.7 Hz, 1H, H-1 ), 6.81 (m, 1H, furan H-4), 7.05 (s, 1H, pyridine
H-5), 7.53 (m, 1H, furan H-3), 8.07 (dd, 1H, furan H-5), 8.44 (s, 1H, NH); 13C NMR
d 19.1 (CH3), 60.7 (C60), 69.7 (C40), 71.7 (C20), 78.6 (C30), 81.6 (C50), 83.6 (C10), 104.8
(C4), 113.0 (C3), 115.8 (CN), 120.1 (furan C4), 139.8 (furan C3), 141.8 (C5), 146.7
(C6), 147.9 (furan C5), 153.0 (furan C2), 162.1 (C2); MS m=z 380; Anal. Calcd for
C17H20N2SO6: C, 53.68; H, 5.26; N, 7.37. Found: C, 54.05; H, 5.49; N, 7.60.
1
7c. Yield 88%, mp 200ꢀC; IR 3660–3240 (OH and NH), 2213 (CN) cmꢁ1; H
NMR d 1.29 (t, J ¼ 6.5 Hz, 3H, CH3), 2.86 (q, 2H, CH2), 3.25–4.07 (m, 6H, 2H-60,
H-50, H-40, H-30, H-20 and 3H, OCH3 and 1H, pyridine H-4), 4.47 (s, 1H, 20-OH),
0
5.18 (m, 3H, 30-OH, 40-OH and 60-OH), 5.64 (d, J1 –2 ¼ 9.5 Hz, 1H, H-1 ), 7.36
(m, 4H, Ar-H and 1H, pyridine H-5), 8.20 (s, 1H, NH); 13C NMR d 15.8 (CH3),
24.9 (CH2), 55.2 (OCH3), 60.7 (C60), 69.7 (C40), 71.8 (C20), 78.6 (C30), 81.5 (C50),
83.6 (C10), 105.1 (C4), 114.0 (C3), 115.9 (CN), 126.5–152.8 (Ar-C), 156.3 (C5),
159.6 161.8 (C2); MS m=z 434; Anal. Calcd for C21H26N2SO6: C, 58.06; H, 5.99;
N, 6.45. Found: C, 58.33; H, 6.16; N, 6.69.
0
0
1
7d. Yield 85%, mp 205ꢀC IR 3680–3210 (OH and NH), 2212 (CN) cmꢁ1; H
NMR d 1.28 (t, J ¼ 6.6 Hz, 3H, CH3), 2.86 (q, 2H, CH2), 3.22–4.06 (m, 6H, 2H-
60, H-50, H-40, H-30, H-20 and 1H, pyridine H-4), 4.45 (t, J ¼ 7.2 Hz, 1H, 20-OH),
5.04 (d, J ¼ 6.9 Hz, 1H, 30-OH), 5.22 (d, J ¼ 9.0 Hz, 1H, 40-OH), 5.43 (d, J ¼ 7.6

Synthesis of 2-(b-D-Glycopyranosylthio) Pyridines
1743
0
Hz, 1H, 60-OH), 5.62 (d, J1 –2 ¼ 9.9 Hz, 1H, H-1 ), 6.80 (m, 1H, furan H-4), 7.01
13
0
0
(s, 1H, pyridine H-5), 7.52 (d, 1H, furan H-3), 8.04 (m, 1H, furan H-5), 8.36 (s,
1H, NH); C NMR d 15.6 (CH3), 24.0 (CH2), 60.6 (C60), 69.6 (C40), 71.7 (C20),
72.4 (C30), 78.5 (C50), 83.6 (C10), 102.9 (C4), 111.8 (C3), 115.3 (CN), 126.1 (furan
C4), 140.5 (C5), 146.4 (C6), 147.8 (furan C5), 157.2 (furan C2), 162.5 (C2); MS
m=z 394; Anal. Calcd for C18H22N2SO6: C, 54.82; H, 5.58; N, 7.11. Found: C,
55.17; H, 5.80; N, 7.43.
1
7e. Yield 86%, mp 194ꢀC; IR 3630–3190 (OH and NH), 2210 (CN) cmꢁ1; H
NMR d 2.41 (s, 3H CH3), 3.40–4.02 (m, 6H, 2H-60, H-50, H-40, H-30, H-20 and 3H,
OCH3 and 1H, pyridine H-4), 4.82 (M, 3H, 20-OH, 30-OH and 40-OH), 5.06 (s, 1H,
0
60-OH), 5.60 (d, J1 –2 ¼ 10.1 Hz, 1H, H-1 ), 7.35 (m, 4H, Ar-H and 1H, pyridine
0
0
13
H-5), 8.08 (s, 1H, NH); C NMR d 19.0 (CH3), 55.4 (OCH3), 60.5 (C60), 68.3
(C40), 70.2 (C20), 74.9 (C30), 79.9 (C50), 84.7 (C10), 102.0 (C4), 113.6 (C3), 115.9
(CN), 125.8-152.9 (Ar-C), 156.9 (C5), 158.1 (C6), 161.9 (C2); MS m=z 420; Anal.
Calcd for C20H24N2SO6: C, 57.14; H, 5.71; N, 6.67. Found: C, 57.53; H, 5.90; N, 6.94.
7f. Yield 85%, mp 190ꢀC; IR 3700-3260 (OH and NH), 2220 (CN) cmꢁ1; MS
m=z 380; Anal. Calcd for C17H20N2SO6: C, 53.68; H, 5.26; N, 7.37. Found: C, 54.11;
H, 5.43; N, 7.75.
1
7g. Yield 88%, mp 188ꢀC; IR 3600–3200 (OH and NH), 2214 (CN) cmꢁ1; H
NMR d 1.28 (t, J ¼ 6.2 Hz, 3H, CH3), 2.86 (q, 2H, CH2), 3.42–3.98 (m, 6H, 2H-60,
H-50, H-40, H-30, H-20 and 3H, OCH3 and 1H, pyridine H-4), 4.50 (d, J ¼ 8.8 Hz, 2H,
0
20-OH and 30-OH), 5.60 (d, J1 –2 ¼ 10.1 Hz, 1H, H-1 ), 7.40 (m, 4H, Ar-H and 1H,
pyridine H-5), 8.17 (s, 1H, NH); 13C NMR d 17.9 (CH3), 24.5 (CH2), 55.2 (OCH3),
60.2 (C60), 68.3 (C40), 68.7 (C20), 75.0 (C30), 79.6 (C50), 84.1 (C10), 105.1 (C4), 114.0
(C3), 115.9 (CN), 126.4-152.8 (Ar-C), 156.4 (C5), 159.6 (C6), 162.0 (C2); MS m=z
434; Anal. Calcd for C21H26N2SO6: C, 58.06; H, 5.99; N, 6.45. Found: C, 58.44;
H, 6.26; N, 6.78.
0
0
7h. Yield 86%, mp 218ꢀC; IR 3680–3200 (OH and NH), 2215 (CN) cmꢁ1; MS
m=z 394; Anal. Calcd for C18H22N2SO6: C, 54.82; H, 5.58; N, 7.11. Found: C, 55.17;
H, 5.69; N, 7.38.
(2,3,4,6-Tetra-O-acetyl-b-D-glycopyranosylthio)-3-aryl-2-
cyanoacryl imidates (9)
To a solution of 3-aryl-2-cyano(thioacrylamides) 1 (0.01 mol) in aqueous KOH
[0.56 gm (0.01 mol) in 6 mL of distilled water], a solution of 2,3,4,6-tetra-O-acetyl-a-
D-glycopyranosyl bromide 4 (0.011 mol) in 30 mL of acetone was added. The reac-
tion mixture was stirred at room temperature until complete (TLC, one hour), then
evaporated under reduced pressure and the residue was washed with distilled water
to remove KBr. The resulting product was dried and crystallized from chloroform-
petroleum ether 40-60 to give the title compounds 9.

1744
Attia and El-Shehawy
9a. Yield 82%, mp 178ꢀC; IR 2224 (CN), 1752 (CO ester of glucose) cmꢁ1; 1H
NMR d 1.82–2.08 (4s, 12H, 4CH3CO), 3.90 (s, 3H, OCH3), 4.12 (m, 3H, 2H-60 and
0
H-50), 4.94 (m, 3H, H-40, H-30 and H-20), 5.48 (d, J1 –2 ¼ 9.0 Hz, 1H, H-1 ), 6.96 (s,
1H, CH), 7.18 (d, 2H, Ar-H), 8.12 (d, 2H, Ar-H), 10.02 (s, 1H, NH); MS m=z 548;
Anal. Calcd for C25H28N2SO10: C, 54.74; H, 5.11; N, 5.11. Found: C, 55.08; H, 5.26;
N, 5.34.
0
0
9e. Yield 81%, mp 164ꢀC; IR 2228 (CN), 1756 (CO ester of galactose) cmꢁ1; 1H
NMR d 1.90–2.12 (4s, 12H 4CH3CO), 3.88 (s, 3H, OCH3), 4.08 (m, 3H, 2H-60 and H-
0
50), 4.58 (m, 1H, H-40), 5.14 (m, 2H, H-30 and H-20), 5.40 (d, J1 ꢂ2 ¼ 9.2 Hz, 1H, H-1 ),
7.68 (m, 1H, CH and 4H, Ar-H), 9.98 (s, 1H, NH); MS m=z 548; Anal. Calcd for
C25H28N2SO10: C, 54.74; H, 5.11; N, 5.11. Found: C, 54.91; H, 5.28; N, 5.35.
0
0
3-Cyano-2-(2,3,4,6-tetra-O-acetyl-b-D-glycopyranosylthio) pyridines (10)
Method A. 3-Cyano-1,4-dihydropyridine-2-thioglycosides 5 (0.01 mol) were
heated at reflux in dry ethanol (30 mL) with stirring under anhydrous condition
for three minutes, and then allowed to stand overnight. The resulting solid product
was collected by filtration and crystallized from ethanol to afford the title com-
pounds 10.
Method B. A mixture of 9 (0.01 mol) and 2 (0.01 mol) was dissolved in dry
ethanol (30 mL), a few drops of piperidine were then added. The mixture was heated
at 60ꢀC for 3 h, and then allowed to stand overnight. The resulting solid product was
collected by filtration and crystallized from ethanol.
10a. Yield 78%, mp 166ꢀC; IR 2215 (CN), 1755 (CO) cmꢁ1; 1H NMR d 1.94–
2.04 (4s, 12H, 4CH3CO), 2.60 (s, 3H, CH3), 3.85 (s, 3H,OCH3), 4.02 (m, 2H, 2H-60),
4.18 (m, 1H, H-50), 5.05 (t, J ¼ 9.6 Hz, 1H, H-40), 5.20 (t, J ¼ 9.3 Hz, 1H, H-30), 5.55
0
(t, J ¼ 9.7 Hz, 1H, H-20), 6.15 (d, J1 –2 ¼ 10.4 Hz, 1H, H-1 ), 7.14 (d, 2H, Ar-H), 7.32
(s, 1H, pyridine H-5), 7.68 (d, 2H, Ar-H); MS m=z 586; Anal. Calcd for
C28H30N2SO10: C, 57.33; H, 5.12; N, 4.78 Found: C, 57.58; H, 5.26; N, 4.99.
0
0
1
10e. Yield 77%, mp 162ꢀC; IR 2218 (CN), 1752 (CO) cmꢁ1; H NMR d 1.96–
2.08 (4s, 12H, 4CH3CO), 2.62 (s, 3H, CH3), 3.90 (s, 3H, OCH3), 4.05 (m, 2H, 2H-60),
4.28 (t, J ¼ 8.5 Hz, 1H, H-50), 5.21 (m, 1H, H-40), 5.39 (d, J ¼ 8.9 Hz, 1H, H-30), 5.54
0
(m, 1H, H-20), 6.14 (d, J1 –2 ¼ 10.5 Hz, 1H, H-1 ), 77.12 (d, 2H, Ar-H), 7.26 (s, 1H,
pyridine H-5), 7.69 (d, 2H, Ar-H); 13C NMR d 15.4 (CH3), 20.2-23.7 (4CH3CO), 55.3
(OCH3), 61.3 (C60), 66.2 (C40), 67.5 (C20), 70.9 (C30), 74.0 (C50), 80.6 (C10), 114.0
(C3), 115.5 (CN), 127.3-133.2 (Ar-C), 151.5 (C5), 153.7 (C4), 159.6 (C6), 161.7
(C2), 169.3–169.9 (4COCH3); MS m=z 586; Anal. Calcd for C28H30N2SO10: C,
57.33; H, 5.12; N, 4.78. Found: C, 57.60; H, 5.35; N, 5.07.
0
0
3-Cyano-2-(b-D-glycopyranosylthio) pyridines (11)
Dry gaseous ammonia was passed through a solution of protected glycosides 10
(0.5 gm) in dry methanol (20 mL) at 0ꢀC for about 0.5 h, then the reaction mixture

Synthesis of 2-(b-D-Glycopyranosylthio) Pyridines
1745
was stirred at room temperature until TLC indicated complete conversion (4 to 6 h).
The resulting reaction mixture was subsequently concentrated under reduced pres-
sure at 40ꢀC to afford a solid residue which was crystallized from methanol to furnish
the title compounds 11.
11a. Yield 89%, mp 200ꢀC; IR 3650–3200 (OH), 2216 (CN) cmꢁ1; MS m=z
418; Anal. Calcd for C20H22N2SO6: C, 57.42; H, 5.26; N, 6.70. Found: C, 57.69;
H, 5.51; N, 6.94.
11e. Yield 87%, mp 212ꢀC; IR 3600–3160 (OH), 2218 (CN) cmꢁ1; 1H NMR d
2.56 (s, 3H, CH3), 3.34–3.80 (m, 6H, 2H-60, H-50, H-40, H-30 and H-20), 3.84 (s, 3H,
OCH3), 4.52 (m, 2H, 20-OH and 30-OH), 4.96 (d, J ¼ 9.4 Hz, 1H, 40-OH), 5.36 (d,
0
J ¼ 9.7 Hz, 1H, 60-OH), 5.56 (d, J1 –2 ¼ 10.3 Hz, 1H, H-1 ), 7.08 (d, 2H, Ar-H),
7.25 (s, 1H, pyridine H-5), 7.60 (d, 2H, Ar-H); MS m=z 418; Anal. Calcd for
C20H22N2SO6: C, 57.42; H, 5.26; N, 6.70. Found: C, 57.74; H, 5.48; N, 6.98.
0
0
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Received August 14, 2002
Accepted March 13, 2003