September 2011
Synthesis and Antiviral Activity of New Substituted Pyrimidine Glycosides
1037
1-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyrano-
syl)-5-cyano-6-phenylpyrimidin-4(1H)-one (13a). Yield ¼ 2.11
g, 78 %; m.p. 150-151ꢀC. ir (KBr) m: 3317 (NH), 1737(C¼¼O),
1-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-5-cyano-6-(4-
methoxy- phenyl)-pyrimidin-4(1H)-one (14c). Yield ¼ 0.32 g,
83%; m.p. 290-292ꢀC. ir (KBr) m: 4362-3995 (OH), 3324
1
1668 (C¼¼O), 2203 (CN) cmꢁ1; H nmr (DMSO-d6): d ¼ 1.75
(NH), 1674 (C¼¼O), 2207 (CN) cmꢁ1
;
1H nmr (DMSO-d6): d
(s, 3 H, NHAc), 1.94, 1.99, 2.00 (3 s, 9 H, 3 OAc), 3.95-4.11
(m, 3 H, H-50, H-60), 4.54 (m, 1 H, H-20), 5.15 (m, 1 H, H-40),
5.30 (m, 1 H, H-30), 5.49 (d, 1 H, J ¼ 9.3 Hz, H-10), 7.77 (d,
1 H, J ¼ 7.5 Hz, NHAc), 7.37-7.47 (m, 5 H, ArAH). EI-MS:
m/z ¼ 542 [Mþ]. Anal. Calcd for C25H26N4O10 (542.50): C
55.35, H 4.83, N 10.32. Found: C 55.21, H 4.77, N 10.13.
1-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyrano-
syl)-5-cyano-6-(4-methylphenyl)-pyrimidin-4(1H)-one (13b). Yield
¼ 2.22 g, 80 %; m.p. 242-243ꢀC. ir (KBr) m: 3319 (NH),
¼ 1.73 (s, 3 H, NHAc), 3.39-3.58 (m, 8 H, H-30, H-40, H-50,
H-60, OCH3), 3.88 (m, 1 H, H-20), 5.20-5.30 (m, 3 H, 3 OH),
5.40 (d, 1 H, J ¼ 9.5 Hz, H-10), 7.21 (d, J ¼ 10.3 Hz, 2 H,
ArAH), 7.39 (d, J ¼ 10.3 Hz, 2 H, ArAH), 7.90 (d, 1 H, J ¼
8.5 Hz, NHAc). EI-MS: m/z ¼ 446 [Mþ]. Anal. Calcd for
C20H22N4O8 (446.41): C 53.81, H 4.96, N 12.55. Found: C
53.60, H 4.83, N 12.33.
REFERENCES AND NOTES
1738 (C¼¼O), 1668 (C¼¼O), 2205 (CN) cmꢁ1
;
1H nmr
(DMSO-d6): d ¼ 1.76 (s, 3 H, NHAc), 1.97, 2.00, 2.05 (3 s,
9 H, 3 OAc), 2.36 (s, 3 H, CH3), 4.25-4.45 (m, 4 H, H-20,
H-50, H-60), 5.20-5.30 (m, 1 H, H-40), 5.43 (m, 1 H, H-30),
5.58 (d, 1 H, J ¼ 9.4 Hz, H-10), 7.21 (d, J ¼ 10.3 Hz, 2 H,
Ar-H), 7.39 (d, J ¼ 10.3 Hz, 2 H, ArAH), 7.80 (d, 1 H, J
¼ 7.5 Hz, NHAc). EI-MS: m/z ¼ 556 [Mþ]. Anal. Calcd
for C26H28N4O10 (556.52): C 56.11, H 5.07, N 10.06.
Found: C 56.00, H 4.89, N 9.97.
[1] Brown, D. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R.; Rees, C. W., Eds.; Pergamon Press: Oxford, 1996;
Vol. 3, Chapter 2. 13.
[2] Malibu, M.; Kappe, C. O. J Comb Chem 2007, 9, 275.
[3] Gadhachanda, V. R.; Wu, B.; Wang, Z.; Kuhen, K. L.;
Caldwell, J.; Zondler, H.; Walter, H.; Havenhand, M.; He, Y. Bioorg
Med Chem Lett 2007, 17, 260.
[4] Agarwal, A.; Srivastava, K.; Purib, S. K.; Chauhana, P. M.
S. Bioorg Med Chem 2005, 13, 4645.
1-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyranosyl)-
5-cyano-6-(4-methoxyphenyl)-pyrimidin-4(1H)-one (13c). Yield
¼ 2.14 g, 75 %; m.p. 263-264ꢀC. ir (KBr) m: 3324 (NH), 1740
(C¼¼O), 1672 (C¼¼O), 2206 (CN) cmꢁ1; 1H nmr (DMSO-d6): d ¼
1.78 (s, 3 H, NHAc), 1.96, 1.99, 2.02 (3 s, 9 H, 3 OAc), 3.53 (s, 3
H, OCH3), 4.07-4.19 (m, 3 H, H-50, H-60), 4.33 (m, 1 H, H-20),
5.32 (m, 1 H, H-40), 5.50 (t, 1 H, J ¼ 9.5 Hz, H-30), 5.60 (d, 1 H, J
¼ 9.2 Hz, H-10), 7.19 (d, J ¼ 10.3 Hz, 2 H, ArAH), 7.33 (d, J ¼
10.3 Hz, 2 H, ArAH), 7.79 (d, 1 H, J ¼ 7.5 Hz, NHAc). EI-MS:
m/z ¼ 572 [Mþ]. Anal. Calcd for C26H28N4O11 (572.52): C 54.54,
H 4.92, N 9.78. Found: C 54.32, H 4.81, N 9.57.
1-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-6-aryl-5-
cyano-pyrimidin-4(1H)-ones (14a-c). A solution of 13a-c
(0.5 g) in a 1:1 mixture (50 mL) of methanol and conc. ammo-
nia (25%) was stirred at room temperature for 8 h. The
reaction mixtures were concentrated under reduced pressure.
The residue were recrystallized from methanol to give 14a-c in
83-90% yields.
[5] Chang, L. C. W.; Spanjersberg, R. F.; von Frijtag Drabbe
Kunzel, K.; Mulder–Krieger, T.; Van DenHout, G.; Beukers, M. W.;
Brussee, J.; Jzerman, A. P. J Med Chem 2004, 47, 6529.
[6] Capdeville, R.; Buchdunger, E.; Zimmermann, J.; Matter,
A.; Glivec, S. T. Nat Rev Drug Discov 2002, 1, 493.
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Nucleosides Nucleotides Nucleic Acids 2009, 28, 261.
[8] Zaki, M. E. A.; Soliman, H. A.; Hiekal, O. A.; Rashad, A.
E. Z Naturforsch 2006, 61c, 1.
[9] Jain, K. S.; Chitre, T. S.; Miniyar, P. B.; Kathiravan, M.
K.; Bendre, V. S.; Veer, V. S.; Shahane, S. R.; Shishoo, C. J. Curr Sci
2006, 90, 793.
[10] Kappe, C. O. Eur J Med Chem 2000, 35, 1043.
[11] Deres, K.; Schroder, C. H.; Paessens, A.; Goldmann, S.; Hacker,
H. J.; Weber, O.; Kraemer, T.; Niewoehner, U.; Pleiss, U.; Stoltefuss, J.;
Graef, E.; Koletzki, D.; Masantschek, R. N. A.; Reimann, A.; Jaeger, R.;
Grob, R.; Beckermann, B.; Schlemmer, K.-H.; Haebich, D.; Rubsamen-
Waigmann, H. Science 2003, 299, 893.
1-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-5-cyano-6-phe-
nyl-pyrimidin-4(1H)-one (14a). Yield ¼ 0.34 g, 90%; m.p.
276-277ꢀC. ir (KBr) m: 4351-3986 (OH), 3315 (NH), 1668
[12] Lengar, A.; Kappe, C. O. Org Lett 2004, 6, 771.
[13] Ganzevoort, W.; Rep, A.; Bonsel, G. J.; de Vries, J. I.;
Wolf, H. Hypertension 2004, 22, 1235.
1
(C¼¼O), 2204 (CN) cmꢁ1; H nmr (DMSO-d6): d ¼ 1.68 (s, 3
[14] Hegab, M. I.; Hassan, N. A.; Rashad, A. E.; Fahmy, A. A.;
Abdel Megeid, F. M. E. Phosphorus Sulfur Silicon Relat Elem 2007,
182, 1535.
H, NHAc), 3.32-3.50 (m, 4 H, H-40, H-50, H-60), 3.77-4.88 (m,
2 H, H-20, H-30), 5.16-5.26 (m, 3 H, 3 OH), 5.36 (d, 1 H, J ¼
9.4 Hz, H-10), 7.30-7.40 (m, 5 H, ArAH), 7.90 (d, 1 H, J ¼
8.5 Hz, NHAc). EI-MS: m/z ¼ 416 [Mþ]. Anal. Calcd for
C19H20N4O7 (416.39): C 54.80, H 4.84, N 13.45. Found: C
54.60, H 4.71, N 13.37.
1-(2-Acetamido-2-deoxy-b-D-glucopyranosyl)-5-cyano-6-(4-
methyl- phenyl)-pyrimidin-4(1H)-one (14b). Yield ¼ 0.34 g,
88%; m.p. 288-289ꢀC. ir (KBr) m: 4360-3990 (OH), 3317
[15] Gholap Atul, R.; Toti Kiran, S.; Shirazi, F.; Deshpande
Mukund, V.; Srinivasan Kumar, V. Tetrahedron 2008, 64, 10214.
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kla, P. K.; Ram, V. J. Bioorg Med Chem Lett 2000, 10, 703.
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Future; Chapman and Hall: New York, 1997.
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schen Chemie, Vol. E9; Schaumann, E., Ed.; G. Thieme Verlag: Stutt-
gart, 1996.
(NH), 1669 (C¼¼O), 2205 (CN) cmꢁ1
;
1H nmr (DMSO-d6): d
¼ 1.69 (s, 3 H, NHAc), 2.38 (s, 3 H, CH3), 3.19-3.29 (m, 4 H,
H-40, H-50, H-60, 3.70-3.80 (m, 2 H, H-20, H-30), 5.15-5.21 (m,
3 H, 3 OH), 5.38 (d, 1 H, J ¼ 9.6 Hz, H-10), 7.22 (d, J ¼ 10.3
Hz, 2 H, ArAH), 7.41 (d, J ¼ 10.3 Hz, 2 H, ArAH), 7.88 (d,
1 H, J ¼ 8.5 Hz, NHAc). EI-MS: m/z ¼ 430 [Mþ]. Anal.
Calcd for C20H22N4O7 (430.41): C 55.81, H 5.15, N 13.01.
Found: C 55.68, H 5.04, N 12.92.
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R.; Moss, J.; Van Caesbroeck, D.; De Broe, M. E.; Clin Br J Pharma-
col 1998, 46, 21.
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Abdel-Mageed, S. M.; Rezki, N. Nucleosides Nucleotides Nucleic
Acids 2007, 26, 423.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet