F. V. Singh et al. / Bioorg. Med. Chem. Lett. 16 (2006) 2734–2737
2737
J.; Oster, C.; Franke, E.; Grogl, M.; Bermann, J. D. Clin.
Infect Dis. 1994, 18, 83.
15. (a) Saxena, A. S.; Goel, A.; Ram, V. J. Synlett 2002, 1491;
(b) Agarwal, N.; Saxena, A. S.; Farhanullah; Goel, A.;
Ram, V. J. Tetrahedron 2002, 58, 8793.
16. (a) Tominaga, Y.; Ushirogochi, A.; Matsuda, Y.
J. Heterocycl. Chem. 1987, 24, 1557; (b) Tominaga, Y.;
Ushirogochi, A.; Matsuda, Y.; Kobayashi, G. Chem.
Pharm. Bull. 1984, 32, 3384.
17. General procedure for the synthesis of 2H-pyran-2-ones
3a–h. A mixture of ethyl 2-cyano-3,3-di(methylsulfa-
nyl)acrylate 1 (10 mmol), propiophenone or aryl acetone
(11 mmol), and powdered KOH (12 mmol) in dry DMSO
(50 mL) was stirred at room temperature for 10 h. After
completion, the reaction mixture was poured into ice
water with constant stirring. The precipitate thus obtained
was filtered and purified on a silica gel column using
chloroform as eluent; 3a: Yellow solid; mp 180–182 ꢁC; 1H
NMR (200 MHz, CDCl3) d 2.17 (s, 3H, CH3), 3.02 (s, 3H,
SCH3), 7.48–7.54 (m, 5H, ArH); IR (KBr) 1707 (CO),
2216 cmꢀ1 (CN); MS (FAB) 258 (M++1).
7. (a) Jha, T. K. Trans. R. Soc. Trop. Med. Hyg. 1983, 77,
167; (b) Hentzer, B.; Kobayashi, T. Trop. Med. Parasitol.
1977, 71, 157; (c) Patra, A. Trans. R. Soc. Trop. Med. Hyg.
1963, 57, 266; (d) Thakur, C. P.; Sinha, G. P.; Pandey, A.
K.; Barat, D.; Sinha, P. K. Natl. Med. J. India 1993, 6, 57;
(e) Sundar, S.; Murray, H. W. J. Infect. Dis. 1996, 173,
762.
8. (a) Jha, T. K.; Sundar, S.; Thakur, C. P.; Bachmann, P.;
Karbwang, J.; Fischer, C.; Voss, A.; Berman, J. N. Engl. J.
Med. 1999, 341, 1795; (b) Sundar, S.; Rosenkaimer, F.;
Makharia, M. K.; Goyal, A. K.; Mandal, A. K.; Voss, A.;
Hilgard, P.; Murray, H. W. Lancet 1998, 352, 1821; (c)
Kuhlencord, A.; Maniera, T.; Eibl, H.; Unger, C.
Antimicrob. Agents Chemother. 1992, 36, 1630; (d) Croft,
S. L.; Neal, R. A.; Pendergast, W.; Chang, J. H. Biochem.
Pharmacol. 1987, 36, 2633.
9. Unger, C.; Eibl, H. Lipids 1990, 17, 143.
10. Iven, A. C.; Peacock, C. S.; Worthey, E. A.; Murphy, L.;
Aggarwal, G.; Berriman, M., et al. Science 2005, 309,
436.
11. (a) Banzatti, C.; Mellini, P.; Salvadori, P. Gazz. Chim. Ital.
1987, 117, 259; (b) Dunn, J. P.; Ackerman, N. A.;
Tomolonis, A. J. J. Med. Chem. 1986, 29, 2326; (c) Nakib,
T.; Meegan, M. J.; Looney, A. M.; Burke, M. L. Eur. J.
Med. Chem. 1992, 27, 971.
12. (a) Nakazato, A.; Ohta, K.; Sekiguchi, Y.; Okuyama, S.;
Chaki, S.; Kawashima, Y.; Hatayama, K. J. Med. Chem.
1999, 42, 1076; (b) Nakazato, A.; Sekiguchi, Y.; Ohta, K.;
Chaki, S.; Okuyama, S. Bioorg. Med. Chem. 1999, 7, 2027;
(c) Boyle, E. A.; Mangan, F. R.; Markwell, R. E.; Smith,
S. A.; Thomson, M. J.; Ward, R. W.; Wyman, P. A.
J. Med. Chem. 1986, 29, 894.
13. (a) Victory, P.; Borrell, J. I.; Vidal-Ferran, A.; Montene-
gro, E.; Jimeno, M. L. Heterocycles 1993, 36, 2273; (b)
Victory, P.; Alvarez-Larena, A.; Germain, G.; Kessels, R.;
Piniella, J. F.; Vidal-Ferran, A. Tetrahedron 1995, 51, 235;
(c) Murugan, P.; Shanmugasundaram, P.; Ramakrishnan,
V. T.; Srividya, N.; Ramamurthy, P. Indian J. Chem. 1998,
37B, 737.
18. General procedure for the synthesis of 5. A mixture of 2H-
pyran-2-ones 3a–h (1 mmol), malononitrile (4, 1.2 mmol),
and powdered KOH (1.2 mmol) in dry DMF (5 mL) was
stirred at room temperature for 12–15 h. At the end the
reaction mixture was poured into ice water with vigorous
stirring and finally neutralized with dilute HCl. The solid
thus obtained was filtered and purified on a silica gel
column using chloroform–hexane (1:2) as eluent. Com-
pound 5a: white solid; yield 94%; mp 220–222 ꢁC; 1H
NMR (200 MHz, CDCl3) d 2.16 (s, 3H, CH3), 2.59 (s, 3H,
SCH3), 5.12 (br s, 2H, NH2), 7.20–7.25 (m, 2H, ArH),
7.47–7.50 (m, 3H, ArH); IR (KBr) 2221 (CN), 3348 (NH),
3407 cmꢀ1(NH); MS (FAB) 280 (M++1). Compound 5b:
white solid; yield 91%; mp 200–202 ꢁC; 1H NMR
(200 MHz, CDCl3) d 2.16 (s, 3H, CH3), 2.59 (s, 3H,
SCH3), 5.15 (br s, 2H, NH2), 7.18 (d, J = 8.2 Hz, 2H,
ArH), 7.48 (d, J = 8.2 Hz, 2H, ArH); IR (KBr) 2221 (CN)
3350 (NH), 3413 (NH), cmꢀ1; MS (FAB) 314 (M++1).
Compound 5c: white solid; yield 89%; mp 188–190 ꢁC; 1H
NMR (200 MHz, CDCl3) d 2.19 (s, 3H, CH3), 2.57 (s, 3H,
SCH3), 3.87 (s, 3H, OCH3), 5.13 (br s, 2H, NH2), 7.00 (d,
J = 8.6 Hz, 2H, ArH), 7.17 (d, J = 8.6 Hz, 2H, ArH); IR
(KBr) 2228 (CN) 3364 (NH), 3457 (NH) cmꢀ1; MS (FAB)
310 (M++1).
14. Khaidem, I. S.; Singh, S. L.; Singh, L. R.; Khan, M. Z. R.
Indian J. Chem. 1996, 35B, 911.