A stereoselective synthesis of a 2-functionalized-methyl-1β-methylcarbapenem key intermediate via decarboxylation

Abstract

An efficient synthesis of a key intermediate 2a for the synthesis of 2-functionalized methyl-1β-methylcarbapenem antibiotics 1 has been realized via a stereoselective decarboxylation reaction.

References

1. A. Tomasz, New England J. Med., 1994, 330, 1247; F. C. Tenover and J. M. Hughes, JAMA, 1996, 275, 300.
2. (a) S. Schmitt, T. N. Salzmann, D. Shih and B. G. Christensen, J. Antibiot., 1988, 780; (b) M. Imuta, H. Itani, H. Ona, T. Konoike, S. Uyeo, Y. Kimura, H. Miwa, S. Matsuura and T. Yoshida, Chem. Pharm. Bull., 1991, 39, 672; (c) A. J. Corraz, S. L. Dax, N. K. Dunlap, N. H. Georgopapadakou, D. D. Keith, D. L. Pruess, P. L. Rossman, R. Then, J. Unowsky and C.-C. Wei, J. Med. Chem., 1992, 35, 1828; (d) J. C. Arnould, R. N. Illingworth, W. W. Nichols and R. G. Wilson, Bioorg. Med. Chem. Lett., 1996, 20, 2449.
3. (a) M. Imuta, H. Itani, H. Ona, Y. Hamada, S. Uyeo and T. Yoshida, Chem. Pharm. Bull., 1991, 39, 663; (b) S. Uyeo and H. Itani, Tetrahedron Lett., 1994, 35, 4377; (c) X. E. Hu and T. P. Demuth, Jr., J. Org. Chem., 1998, 63, 1719.
4. (a) W.-B. Choi, H. R. O. Churchill, J. E. Lynch, A. S. Thompson, G. R. Humphrey, R. P. Volante, P. J. Reider and I. Shinkai, Tetrahedron Lett., 1994, 35, 2275; (b) T. Murayama, A. Yoshida, T. Kobayashi and T. Miura, Tetrahedron Lett., 1994, 35, 2271; (c) D. K. Jones, D. C. Liotta, W.-B. Choi, R. P. Volante, P. J. Reider, I. Shinkai, H. R. O. Churchill and J. E. Lynch, J. Org. Chem., 1994, 59, 3749; (d) W.-B. Choi, H. R. O. Churchill, J. E. Lynch, R. P. Volante, P. J. Reider, I. Shinkai, D. K. Jones and D. C. Liotta, J. Org. Chem., 1995, 60, 8367.
5. The crude product was filtered through Celite, washed with aq. Na₂CO₃ and analyzed by ¹H NMR spectroscopy. The major isomer of 8 cleanly gave a > 99∶1 β∶α mixture of 9, while the minor isomer of 8 gave the same 99∶1 β∶α mixture of 9 along with 7–10% ring opened by-product 4a.
6. During the desilylation, 7–10% of 4c was formed.
7. The C-1 configuration was determined by conversion of 2a to the known acetate [ref. 3(a)]. The spectroscopic data of the acetate were found to be identical to those reported.
8. Selected data for 2a: δ_H(CDCl₃) 6.43 (br s, 1 H), 4.38 (d, J 19.4, 1 H), 4.25 (d, J 19.4, 1 H), 4.15 (m, 1 H), 3.85 (dd, J 1.9, 5.0, 1 H), 3.25 (br s, 1 H), 2.93 (dd, J 1.9, 4.6, 1 H), 2.84 (1 H, m), 1.19 (d, J 7.0, 3 H), 1.16 (d, J 6.3, 3 H), 0.85 (s, 9 H), 0.06 (s, 3 H), 0.04 (s, 3 H); δ_C(CDCl₃) 211.8, 168.5, 67.9, 65.3, 61.8, 51.4, 44.7, 25.8, 22.6, 17.9, 12.4, –4.3, –4.9.