Synthetic studies of nucleoside antibiotics: a formal synthesis of (+)-sinefungin

Abstract

A formal synthesis of (+)-sinefungin 1 is described. The C-6′ and C-9′ stereogenic centers of sinefungin were constructed stereoselectively by efficient catalytic asymmetric syntheses. The key strategy for the construction of the C-6′ stereocenter involves alkylation of a protected ribose-derived triflate with alkynyl-lithium, Sharpless asymmetric epoxidation of the corresponding allylic alcohol followed by a regioselective epoxide-ring opening with diisopropoxytitanium diazide. The C-9 amino acid stereochemistry was established by a rhodium chiral bisphosphine-catalyzed asymmetric hydrogenation of an α-(acylamino)acrylate derivative. The resulting amino acid derivative has been previously converted to (+)-sinefungin 1.

References

1. R. L. Hamil and M. M. Hoehn, J. Antibiot., 1973, 26, 463.
2. (a) R. J. Suhadolnik, Nucleotides as Biological Probes, Wiley, New York, 1979, pp. 19–23; (b) C. S. G. Pugh, R. T. Borchardt and H. O. Stone, J. Biol. Chem., 1978, 253, 4075 and references cited therein.
3. (a) M. T. McCamnon and L. W. Parks, J. Bacteriol., 1981, 145, 106; (b) R. W. Fuller and R. Nagarajan, Biochem. Pharmacol., 1978, 27, 1981 and references cited therein.
4. E. Zweygerth, D. Schillinger, W. Kaufmann and D. Roettcher, Trop. Med. Parasitol., 1986, 37, 255.
5. For synthetic studies, see; (a) Y. Mizuno, K. Tsuchida and H. Tampo, Chem. Pharm. Bull., 1984, 32, 2915; (b) A. R. Moorman, T. Martin and R. T. Borchardt, Carbohydr. Res., 1983, 113, 233; (c) J. W. Lyga and J. A. Secrist, III, J. Org. Chem., 1983, 48, 1982.
6. For total synthesis, see; (a) D. H. R. Barton, S. D. Gero, B. Quiclet-Sire and M. Samadi, J. Chem. Soc., Perkin Trans. 1, 1991, 983; (b) M. P. Maguire, P. L. Feldman and H. Rapoport, J. Org. Chem., 1990, 55, 948; (c) J. G. Buchanan, A. Flinn, P. H. Mundill and R. H. Wightman, Nucleosides, Nucleotides, 1986, 5, 313; (d) M. Geze, P. Blanchard, J. L. Fourrey and M. Robert-Gero, J. Am. Chem. Soc., 1983, 105, 7638; (e) G. A. Mock and J. G. Moat, Nucleic Acids Res., 1982, 10, 6223.
7. For synthesis of sinefungin analogues, see; (a) D. H. R. Barton, S. D. Gero, F. Lawrence, M. Robert-Gero, B. Quiclet-Sire and M. Samadi, J. Med. Chem., 1992, 35, 63; (b) D. H. R. Barton, S. D. Gero, G. Negron, B. Quiclet-Sire, M. Samadi and C. Vincent, Nucleosides, Nucleotides, 1995, 14, 1619; (c) P. Peterli-Roth, M. P. Maguire, E. Leon and H. Rapoport, J. Org. Chem., 1994, 59, 4186.
8. A. K. Ghosh and W. Liu, J. Org. Chem., 1996, 61, 6175.
9. (a) A. K. Ghosh, S. P. McKee, W. M. Sanders, P. L. Darke, J. A. Zugay, E. A. Emini, W. A. Schleif, J. C. Quintero, J. R. Hu and P. S. Anderson, Drug Des. Discovery, 1993, 10, 77; (b) P. A. Levene and E. T. Stiller, J. Biol. Chem., 1934, 104, 299.
10. H. Kotsuki, I. Kadota and M. Ochi, Tetrahedron Lett., 1990, 31, 4609.
11. (a) R. A. Johnson and K. B. Sharpless, in Catalytic Asymmetric Synthesis, ed. I. Ojima, VCH Publishers, New York, 1993, pp. 103–158; (b) Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune and K. B. Sharpless, J. Am. Chem. Soc., 1987, 109, 5765.
12. A. K. Ghosh and Y. Wang, J. Org. Chem., 1999, 64, 2789.
13. M. Caron, P. R. Carlier and K. B. Sharpless, J. Org. Chem., 1988, 53, 5185.
14. Z. Liu, B. Classon and B. Samuelsson, J. Org. Chem., 1990, 55, 4273.
15. U. Schmidt, A. Lieberknecht and J. Wild, Synthesis, 1984, 53.
16. J. W. Scott, D. D. Keith, G. Nix, Jr., D. R. Parrish, S. Remington, G. P. Roth, J. M. Townsend, D. Valentine, Jr. and R. Yang, J. Org. Chem., 1981, 46, 5086.
17. (a) W. S. Knowles, M. J. Sabacky, B. D. Vineyard and D. J. Weinkau, J. Am. Chem. Soc., 1975, 97, 2567; (b) B. D. Vineyard, W. S. Knowles, M. J. Sabacky, G. L. Bachman and D. J. Weinkau, J. Am. Chem. Soc., 1977, 99, 5946.