2304
M.-C. Liu et al. / Bioorg. Med. Chem. Lett. 11 (2001) 2301–2304
virus (333 strain), hepatitis B virus, and human
immunodeficiency virus (HIV-IIIB) in vitro. None of
the compounds showed toxicity or activity against these
respective virus strains up to the maximum tested
concentrations of 50, 10, 100 mM.
J. A. J. M.; Sheldon, R. A. Tetrahedron: Asymmetry 1991, 2,
359.
18. Compound 14: oil [a]2D2 +4.5ꢁ (c 0.1, MeOH); H NMR
1
(DMSO-d6) d 1.29 (s, 3H, CH3), 3.60 (s, 2H, CH2), 4.20 (dd,
1H, J=8.0 Hz, 2.4 Hz, 5-HA), 4.30 (t, 1H, J=5.7 Hz, 5-HB),
4.55 (t, 1H, J=4.5 Hz, 4-H), 4.61 (s, 2H, ArCH2), 7.22–7.30
(m, 5H, ArH), 9.30 (bs, 1H, COOH, D2O exchangeable).
Compound 15: oil [a]2D2 ꢀ15.7ꢁ (c 0.1, MeOH; 1H NMR
(DMSO-d6) d 1.48 (s, 3H, CH3), 3.40 (s, 2H, CH2), 4.15 (dd,
1H, J=8.1, 2.7 Hz, 5-HA), 4.32 (t, 1H, J=5.4 Hz, 5-HB), 4.55
(s, 2H, ArCH2), 4.60 (t, 1H, J=3.6 Hz, 4-H), 7.20–7.32 (m,
5H, ArH), 8.20 (bs, 1H, COOH, D2O exchangeable).
Acknowledgements
This research was supported in part by Connecticut
Innovations, Inc.
19. Kim, H. O.; Ahn, S. K.; Alves, A. J.; Beach, J. W.; Jeong,
L. S.; Choi, B. G.; Roey, P. V.; Schinazi, R. F.; Chu, C. K. J.
Med. Chem. 1992, 35, 1987.
1
References and Notes
20. Compound 7: oil, H NMR (CDCl3) d 1.48, 1.55 (s, 3H,
CH3), 2.00, 2.10 (s, 3H, CH3), 3.45, 3.55 (s, 2H, CH2), 4.05–
4.20 (m, 2H, 5-H), 4.64, 4.67 (s, 2H, ArCH2), 6.40–6.47 (m,
1H, 4-H), 7.20–7.32 (m, 5H, ArH). Compound 8: oil, 1H
NMR (CDCl3) d 1.46, 1.53 (s, 3H, CH3), 2.00, 2.10 (s, 3H,
CH3), 3.43, 3.53 (s, 2H, CH2), 4.07–4.22 (m, 2H, 5-H), 4.62,
4.65 (s, 2H, ArCH2), 4.41–6.47 (m, 1H, 4-H), 7.20–7.32 (m,
5H, ArH).
1. Belleau, B.; Dixit, D.; Nguyen-Ba, N.; Kraus, J. L. Abstr.
TCO1, Abst. 5th Int. Conf. AIDS, Montreal, Quebec,
Canada, 1989; p 515.
2. Soudeyns, H.; Yao, X. J.; Gao, Q.; Belleau, B.; Kraus, J. L.;
Nguyen-Ba, N.; Spira, B.; Wainberg, M. A. Antimicrob.
Agents Chemother. 1991, 35, 1386.
3. Chu, C. K.; Beach, J. W.; Jeong, L. S.; Choi, B. G.; Comer,
F. I.; Alves, A. J.; Schinazi, R. F. J. Org. Chem. 1991, 56,
6503.
21. Compound 3: mp 190–192 ꢁC; [a]2D2 ꢀ17.6ꢁ (c 0.1, MeOH);
1H NMR (DMSO-d6) d 1.27 (s, 3H, 40-CH3), 3.49 (d, 2H,
J=6.0 Hz, 50-H), 3.96 (dd, 1H, J=3.0, 6.6 Hz, 20-HA), 4.32
(dd, 1H, J=3.9, 5.7 Hz, 20-HB), 5.19 (t, 1H, 50-OH, D2O
exchangeable), 5.71 (d, 1H, J=7.5 Hz, 5-H), 6.16 (dd, 1H,
J=3.3, 6.2 Hz, 10-H), 7.20, 7.50 (s, 2H, NH2, D2O exchange-
able), 7.87 (d, 1H, J=7.5 Hz, 6-H). Compound 20: mp 212–
4. Beach, J. W.; Jeong, L. S.; Alves, A. J.; Pohl, D.; Kim,
H. O.; Chang, C. N.; Doong, S. L.; Schinazi, R. F.; Cheng,
Y. C.; Chu, C. K. J. Org. Chem. 1992, 57, 2217.
5. Kim, H. O.; Shanmuganathan, K.; Alves, A. J.; Jeong,
L. S.; Beach, J. W.; Schinazi, R. F.; Chang, C. N.; Cheng,
Y. C.; Chu, C. K. Tetrahedron Lett. 1992, 33, 6899.
6. Grove, K. L.; Guo, X.; Liu, S. H.; Gao, Z.; Chu, C. K.;
Cheng, Y. C. Cancer Res. 1995, 55, 3008.
7. Maag, H.; Rydzewski, R. M.; McRoberts, M. J.; Craw-
ford-Ruth, D.; Verheyden, J. P. H.; Prisbe, E. J. J. Med.
Chem. 1992, 35, 1440.
8. O-Yang, C.; Wu, H. Y.; Fraser-Smith, E. B.; Walker,
K. A. M. Tetrahedron Lett. 1992, 33, 37.
9. Waga, T.; Nishizaki, T.; Miyakawa, I.; Ohrui, H.; Meguro,
H. Biosci. Biotechnol. Biochem. 1993, 57, 1433.
10. Nomura, M.; Shuto, S.; Tanaka, M.; Sasaki, T.; Mori, S.;
Shigeta, S.; Matsuta, A. J. Med. Chem. 1999, 42, 2901.
11. Kitano, K.; Miura, S.; Ohrui, H.; Meguro, H. Tetrahedron
1997, 53, 13315.
22
214 ꢁC; [a]D +10.2ꢁ (c 0.1, MeOH); H NMR (DMSO-d6) d
1.41 (s, 3H, 40-CH3), 3.35 (d, 2H, J=6.0 Hz, 50-H), 3.95 (dd,
1H, J=2.4, 6.2 Hz, 20-HA), 4.37 (dd, 1H, J=3.6, 8.0 Hz, 20-
HB), 5.06 (t, 1H, 50-OH, D2O exchangeable), 5.78 (d, 1H,
J=7.4 Hz, 5-H), 6.16 (dd, 1H, J=1.8, 3.2 Hz, 10-H), 7.05, 7.15
(s, 2H, NH2, D2O exchangeable), 7.54 (d, 1H, J=7.5 Hz, 6-
H). Compound 5: mp 192–194 ꢁC; [a]2D2 ꢀ20.2ꢁ (c 0.1, MeOH);
1H NMR (DMSO-d6) d 1.24 (s, 3H, 40-CH3), 3.52 (d, 2H, 50-
H, J=6.0 Hz), 4.02 (dd, 1H, J=2.7, 9.6 Hz, 20-HA), 4.34 (dd,
1H, J=5.7, 9.6 Hz, 20-HB), 5.35 (t, 1H, 50-OH, D2O
exchangeable), 6.14 (dd, 1H, J=2.7, 5.7 Hz, 10-H), 7.55, 7.80
(s, 2H, NH2, D2O exchangeable), 8.21 (d, 1H, J=7.2 Hz, 6-
H). Compound 21: mp 198–200 ꢁC; [a]D22 +10.2ꢁ (c 0.1,
MeOH); 1H NMR (DMSO-d6) d 1.42 (s, 3H, 40-CH3), 3.40 (d,
2H, J=6.0 Hz, 50-H), 4.03 (dd, 1H, J=2.1, 6.2 Hz, 20-HA),
4.34 (dd, 1H, J=3.2, 7.6 Hz, 20-HB), 5.08 (t, 1H, 50-OH, D2O
exchangeable), 6.19 (dd, 1H, J=2.1, 4.7 Hz, 10-H), 7.61, 7.82
(s, 2H, NH2, D2O exchangeable), 7.61 (d, 1H, J=6.9 Hz, 6-
H). Compound 4: mp 191–192 ꢁC; [a]D22 +18.4ꢁ (c 0.1,
MeOH). Compound 26: mp 210–212 ꢁC; [a]D22 ꢀ12.4ꢁ (c 0.1,
MeOH). Compound 6: mp 194–196 ꢁC; [a]D22 +17.2ꢁ (c 0.1,
MeOH). Compound 27: mp 198–200 ꢁC; [a]D22 ꢀ13.2ꢁ (c 0.1,
MeOH).
1
12. Waga, T.; Ohrui, H.; Meguro, H. Nucleosides Nucleotides
1996, 15, 287.
13. Jeong, L. S.; Schinazi, R. F.; Beach, J. W.; Kim, H. O.;
Nampalli, S.; Shanmuganathan, K.; Alves, A. J.; McMillan,
A.; Chu, C. K.; Mathis, R. J. Med. Chem. 1993, 36, 181.
14. Lin, T. S.; Luo, M. Z.; Liu, M. C.; Zhu, Y. L.; Gullen, E.;
Dutschman, G. E.; Cheng, Y. C. J. Med. Chem. 1996, 39,
1757.
15. Belleau, B. R.; Evans, C. A.; Tse, H. L. A.; Jin, H.; Dixit,
D. M.; Mansour, T. S. Tetrahedron Lett. 1992, 33, 6949.
16. Manzocchi, A.; Fiecchi, A.; Santaniello, E. Synthesis
1987, 1007.
22. Kim, H. O.; Schinazi, R. F.; Shanmuganathan, K.; Jeong,
L. S.; Beach, J. W.; Nampalli, S.; Cannon, D. L.; Chu, C. K.
J. Med. Chem. 1993, 36, 519.
23. Okabe, M.; Sun, R. C.; Tam, S. Y. K.; Todaro, L. J.;
Coffen, D. L. J. Org. Chem. 1988, 53, 4780.
17. Emmons, C. H. H.; Kuster, B. F. M.; Vekemans,