6,19-carbon-bridged steroids. Synthesis of 6,19-methano-progesterone

Organic and Biomolecular Chemistry

Volumn 1, Issue 6, 2003, Pages 939-943

  Joselevich, María ^a   Ghini, Alberto A ^a   Burton, Gerardo ^a  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

Author keywords

[No Author keywords available]

Indexed keywords

ADDITION REACTIONS; ALDEHYDES; ATOMS; CALCULATIONS; CARBON; CONFORMATIONS; DERIVATIVES; HYDROLYSIS; MOLECULAR STRUCTURE; SYNTHESIS (CHEMICAL);

DIACETYLOXYBROMOOXIDOPREGNANE; LEWIS ACID; METHANOPROGESTERONE;

ORGANIC COMPOUNDS;

6,19 METHANOPROGESTERONE; 6,19-METHANOPROGESTERONE; DRUG DERIVATIVE; PROGESTERONE; STEROID;

ARTICLE; CHEMICAL MODEL; CHEMICAL STRUCTURE; SYNTHESIS;

MODELS, CHEMICAL; MOLECULAR STRUCTURE; PROGESTERONE; STEROIDS;

EID: 0041318990     PISSN: 14770520     EISSN: None     Source Type: Journal    
DOI: 10.1039/b211974a     Document Type: Article

References (28)

1. A. S. Campos Neves, M. L. Sá e Melo, M. J. S. M. Moreno, E. J. Tavarez da Silva, J. A. R. Salvador, S. P. da Costa and R. M. L. M. Martins, Tetrahedron, 1999, 55, 3255-3264, and references cited therein.
2. G. Burton, M. Galigniana, S. de Lavallaz, A. L. Brachet-Cota, E. M. Sproviero, A. A. Ghini, C. P. Lantos and M. C. Damasco, Mol. Pharmacol., 1995, 47, 535-543.
3. G. P. Vicent, M. C. Monteserin, A. S. Veleiro, G. Burton, C. P. Lantos and M. D. Galigniana, Mol. Pharmacol., 1997, 52, 749-753.
4. A. S. Veleiro, R. Rosenstein, M. L. Grilli, C. Jaliffa, F. Speroni and G. Burton, Bioorg. Med. Chem. Lett., 2003, 13, 343-346.
5. G. Burton, C. P. Lantos and A. S. Veleiro, PCT Int. Appl. WO 02 22.627, 21 Mar 2002, EP Appl. EP 00,119,495.0, 18 Sept 2000.
6. H. Klinzer, D. Bittler, D. Rosenberg, G. Sauer and R. Wiecher, Tetrahedron Lett., 1990, 31, 6171-6174 and references cited therein.
7. J. P. Burkhart, E. W. Huber, F. M. Lanskovics and N. P. Peet, J. Org. Chem., 1992, 57, 5150-5154.
8. For a comparison of the X-ray crystallographic structures of 1 and 3, see ref. 5, Excellent correspondence has been observed between these structures and those calculated using the AM1 semiempirical method.
9. Functionalization of C-19 was achieved by a hypoiodite remote functionalization reaction. The other two major routes for the introducton of substituents at the 100- and/or 19-positions of the steroid nucleus involve the opening of a 5,10-epoxide, and the [3,3] sigmatropic rearrangement of an allylic ether tethered on the 11ß-position and a 5,10-double bond. In both cases, the starting materials are 19-nor steroids. See D. Lesuisse, F. Canu and B. Tric, Tetrahedron, 1994, 50, 8491-8504 and references cited therein.
10. B. E. Maryanoff and A. B. Reitz, Chem. Rev., 1989, 89, 863-927.
11. B. Snider, in Comprehensive Organic Synthesis, ed. B. M. Trost and I. Fleming, Pergamon Press, New York, 1991, Vol. 2, p. 527-561.
12. P. de Armas, J. I. Concepcion, C. G. Francisco, R. Hernandez, J. A. Salazar and E. Suarez, J. Chem. Soc. Perkin Trans 1, 1989, 405-411.
13. P. Kocovsky and F. Turecek, Tetrahedron, 1983, 39, 3621-3626.
14. P. A. Marcotte and C. H. Robinson, Steroids, 1982, 39, 325-342
15. P. Kocovsky, Coll. Czech. Chem. Commun., 1983, 48, 3618-3628 and references cited therein.
16. For other alternatives see E. Vedejs, G. P. Meier and K. H. J. Snoble, J. Am. Chem. Soc., 1981, 103, 2823-2831 and references cited therein.
17. W. E. Childers, P. S. Furth, M.-J. Shih and C. H. Robinson, J. Org. Chem., 1988, 53, 5947-5951 (for sulfur ylides)
18. S. R. Schow and T. C. McMorris, J. Org. Chem., 1979, 44, 3760-3765 (for Wittig reactions with steroids).
19. At least two distinct mechanism are operative for the Wittig reaction depending on the presence or absence of a metal ion at the site of oxaphosphetane formation and this is probably reflected in the observed stereoselectivity. W. J. Ward, Jr. and W. E. McEwen, J. Org. Chem., 1990, 55, 493-500 and references cited therein
20. E. Vedejs and C. F. Marth, J. Am. Chem. Soc., 1989, 111, 1519-1520 and references cited therein.
21. E. Ottow, R. Rohde, W. Schwede and R. Wiecher, Tetrahedron Lett., 1993, 34, 5253-5256.
22. N. H. Andersen, S. W. Hadley, J. D. Kelly and E. R. Bacon, J. Org. Chem., 1985, 50, 4144-4151.
23. 4 was the most effective even without optimization.
24. 1 reactions due to the stabilization of the intermediate homoallylic carbocation, the allylic acetate in 15 would show a similar reactivity.
25. C. A. G. Haasnoot, F. A. A. M. de Leeuw and C. Altona, Tetrahedron, 1980, 36, 2783-2792.
26. D. H. R. Barton and D. O. Jang and J. Cs. Jaszberenyi, Tetrahedron, 1993, 49, 7193-7214, and references cited therein.
27. Chromatographic purification prior to this stage was carried out with the purpose of characterizing compounds 10 and 11 however, extensive decomposition was observed (probably by cleavage of the additional bridge via retroaldolic-type reactions, that would cause a relief of angular and torsional tension). Better yields were obtained when purification was carried out after removal of the hydroxyl group at C-19a (compound 12).
28. T. C. Wong and V. Rutar, J. Am. Chem. Soc., 1984, 106, 7380-7384.