Steroidal Aphidicolin Analogues Derived from Pregnenolone

Abstract

The conversion of pregnenolone into the 3β,5α-, 3α,5α-, 4β,5α-, 3α,4α-, 3α,4β- and 3α,4α-dihydroxy derivatives of 17β-hydroxymethyl-5α-androstane as steroidal analogues of the diterpenoid DNA polymerase α inhibitor, aphidicolin, is described.

References

1. For a review, see: T. Ojasoo, J. P. Ranaud and J. P. Mornon, in Comprehensive Medicinal Chemistry, ed. C. Hansch, Pergamon Press, Oxford, 1990, vol. 3 ch. 16.3, p. 1175.
2. W. Dalziel, B. Hesp, K. M. Stevenson and J. A. J. Jarvis, J. Chem. Soc., Perkin Trans. 1, 1973, 2841.
3. S. Ikegami, T. Taguchi and M. Ohashi, Nature (London), 1978, 275, 458.
4. R. Sheaff, D. Ilsley and R. Kuchta, Biochemistry, 1991, 34, 8590.
5. S. Hiranuma, T. Shimizu, H. Yoshioka, K. Ono, H. Nakane and T. Takahashi, Chem. Pharm. Bull., 1987, 35, 1641.
6. J. A. Boynton and J. R. Hanson, J. Chem. Soc., Perkin Trans. 1, 1995, 2189.
7. J. R. Hanson, P. B. Hitchcock and C. Uyanik, J. Chem. Res, 1998, (S) 682; (M) 2862.
8. J. Staunton and E. J. Eisenbraun, Org. Synth., 1973, Coll. Vol. V, 8.
9. S. Danishefsky, K. Nagasawa and N. Wang, J. Org. Chem., 1975, 40, 1989.
10. T. Sato, J. Otera and H. Nozaki, J. Org. Chem., 1992, 57, 2166.
11. M. Saiah, M. Bessodes and K. Antonakis, Tetrahedron Lett., 1992, 33, 4317.
12. J. F. Eastham and R. Teranishi, Org. Synth., Coll. Vol. IV, 192.
13. E. Winterfeldt, U. Tibtamm, R. Hofmeister and H. Laurent, Ger. Pat., DE 3909770, 1990.
14. J. R. Hanson, P. B. Hitchcock, M. D. Liman and S. Nagaratnam, J. Chem. Soc., Perkin Trans. 1, 1995, 2183.
15. R. C. Cambie, P. S. Rutledge, D. W. Scott and P. D. Woodgate, Aust. J. Chem., 1979, 32, 695.
16. M. Minato, K. Yamamoto and J. Tsuji, J. Org. Chem., 1990, 55, 766.