Modified nucleosides from nitrones: a new and efficient stereoselective approach to isoxazolidinyl thymidine derivatives

Abstract

The addition of the sodium enolate of methyl acetate to the N-benzyl nitrone 4 derived from D-glyceraldehyde affords the 3-substituted isoxazolidin-5-one 6a with a high degree of syn selectivity and in quantitative chemical yield; its further elaboration leads to the preparation of the important isoxazolidine nucleoside analogue 2a in enantiomerically pure form.

References

1. D. M. Huryn and M. Okabe, Chem. Rev., 1992, 92, 1745.
2. M. Kassou and S. Castillon, J. Org. Chem., 1997, 62, 3696; R. R. Talekar and R. H. Wightman, Tetrahedron, 1997, 53, 3831 and references cited therein.
3. H. Jin, M. A. Siddiqui, C. A. Evans, H. L. A. Tse, T. S. Mansour, M. D. Goodyear, P. Ravenscroft and C. D. Beels, J. Org. Chem., 1995, 60, 262 and references cited therein.
4. J. M. J. Tronchet, M. Iznaden, F. Barbalatrey, H. Dhimane, A. Ricca, J. Balzarini and E. Declercq, Eur. J. Med. Chem., 1992, 27, 555; J. M. J. Tronchet, M. Iznaden, F. Barbalatrey, I. Komaromi, N. Dolatshami and G. Berbardinelli, Nucleosides Nucleotides, 1995, 14, 1737.
5. U. Chiacchio, G. Gumina, A. Rescifina, R. Romero, N. Uccella, F. Casuscelli, A. Piperno and G. Romeo, Tetrahedron, 1996, 52, 8889; G. Sindona, C. Siciliano, G. Giglio, A. Napoli, A. Leggio, A. Liguori and A. Procopio, Synth. Commun., 1997, 26, 4211.
6. Y. Xiang, Y. Gong and K. Zhao, Tetrahedron Lett., 1996, 37, 4877 During the refereeing process of this manuscript a similar approach based on the diastereoselective Michael addition of hydroxylamine to unsaturated esters has been reported by the same authors. See Y. Xiang, H.-J. Gi, D. Niu, R. F. Schinazi and K. Zhao, J. Org. Chem., 1997, 62, 7430.
7. P. Merino, A. Lanaspa, F. L. Merchan and T. Tejero, Tetrahedron Lett., 1997, 38, 1813; P. Merino, A. Lanaspa, F. L. Merchan and T. Tejero, J. Org. Chem., 1996, 61, 9028; A. Dondoni, F. Junquera, F. L. Merchan, P. Merino and T. Tejero, J. Chem. Soc., Chem. Commun., 1995, 2127.
8. D. D. Dhavale and C. Trombini, J. Chem. Soc., Chem. Commun., 1992, 1268; C. Camiletti, D. D. Dhavale, F. Donati and C. Trombini, Tetrahedron Lett., 1995, 36, 7293.
9. Y. Kita, F. Itoh, O. Tamura, Y. Y. Ke and Y. Tamura, Tetrahedron Lett., 1987, 28, 1431; Y. Kita, O. Tamura, F. Itoh, H. Kishino, T. Miki, M. Kohno and Y. Tamura, J. Chem. Soc., Chem. Commun., 1988, 761.
10. P. Merino, S. Franco, F. L. Merchan and T. Tejero, Tetrahedron: Asymmetry, 1997, 8, 3489.
11. P. Merino, E. Castillo, F. L. Merchan and T. Tejero, Tetrahedron: Asymmetry, 1997, 8, 1725; P. Merino, S. Anoro, E. Castillo, F. L. Merchan and T. Tejero, Tetrahedron: Asymmetry, 1996, 7, 1887.
12. T. Fujisawa, Y. Koorijama and M. Shimizu, Tetrahedron Lett., 1996, 37, 3881.
13. T.-J. Sturm, A. E. Marolewski, E. S. Rezenka and S. K. Taylor, J. Org. Chem., 1989, 54, 2039.
14. T. Niahimura and T. Iwai, Chem. Pharm. Bull., 1964, 12, 352.
15. H. Vorbruggen, K. Krolikiewicz and B. Bennua, Chem. Ber., 1981, 114, 1234.
16. G. M. Sheldrick, Acta Crystallogr., 1990, A46, 467.
17. G. M. Sheldrick, SHELXL-93, Program for the Refinement of Crystal Structures, University of Gottingen, Germany, 1993.