Oxido-bridged neurosteroid analogues. Synthesis of 2,19-oxido-allopregnanolone

Arkivoc

Volumn 2003, Issue 10, 2003, Pages 468-476

  Eduardo, Silvina L ^a   Ghini, Alberto A ^a   Burton, Gerardo ^a  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

Author keywords

2,19 Oxido allopregnanolone; 4,19 oxido allopregnanolone; Neurosteroid; Oxido bridged steroid

Indexed keywords

19 HYDROXY 2ALPHA,3ALPHA EPOXYPREGNANE; 19 HYDROXYPREGNENOLONE 3 ACETATE; 3ALPHA HYDROXY 2,19 OXIDO 5ALPHAH PREGNAN 20 ONE; 3ALPHA HYDROXY 5ALPHAH PREGNAN 20 ONE; 4BETA,19 OXIDO 3ALPHA HYDROXY 5ALPHAH PREGNAN 20 ONE; BRIDGED COMPOUND; NEUROSTEROID; SILANE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CYCLIZATION; DESILYLATION; DRUG STRUCTURE; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

EID: 3242673298     PISSN: 14246376     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (18)

1. Gasior M.; Carter R. B.; Witkin J. M. Trends Pharmacol. Sci. 1999, 20, 107.
2. Lambert, J. J.; Belelli, D.; Hill-Venning, C.; Peters, J. A. Trends Pharmacol. Sci. 1995, 16, 295.
3. Hamilton, N. M. Curr. Topics Med. Chem. 2002, 2, 887.
4. Beekman M.; Ungard J. T.; Gasior M.; Carter R. B.; Dijkstra D.; Golberg S. R.; Witkin J. M. J. Pharmacol. Exp. Ther. 1998, 284, 868.
5. Phillips, G. H.; Ayres, B. E.; Bailey, E. J.; Ewan, G. B.; Looker, B. E.; May, P. J. J. Steroid Biochem. 1979, 11, 79.
6. Anderson, A.; Boyd, A. C.; Campbell, A. C.; Gemmel, D. K.; Hamilton, N. M.; Hill, D. R.; Hill-Venning, C.; Lambert, J. J.; Maidment, M. S.; May, V.; Marshall, R. J.; Peters, J. A.; Rees, D. C.; Stevenson, D.; Sundaram, H. J. Med. Chem., 1997, 40, 1668.
7. Burton, G.; Galignana, M. D.; de Lavallaz, S.; Brachet-Cota, A. L.; Sproviero, E. M.; Ghini, A. A.; Lantos, C. P.; Damasco, M. C. Mol. Pharmacol. 1995, 47, 535
8. See for example T. W. Stone (Editor), CNS Neurotransmitters and Neuromodulators. Neuroactive Steroids, Chapters 2 and 4, CRC Press, 1996.
9. Veleiro, A. S.; Rosenstein, R.; Jaliffa, C.; Grilli, M. L.; Speroni, F.; Burton, G. Bioorg. Med Chem. Letters 2003, 13, 343.
10. Anderson, A.; Boyd, A. C.; Clark, J. K.; Fielding, L.; Gemmell, D. K.; Hamilton, N. M.; Maidment, M. S.; May, V.; McGuire, R.; Mc Phail, P.; Sansbury, F. H.; Sundaram, H.; Taylor, R. J. Med. Chem., 2000, 43, 4118.
11. Burkhart, J.P.; Huber, E.W.; Laskovics, F.M.; Peet, N.P. J. Org. Chem., 1992, 57, 5150-5154.
12. Joselevich, M.; Ghini, A. A.; Burton, G. Org. Biomol. Chem. 2003, 1, 939.
13. In the TBDMS derivative 10, any interaction between the double bond and the C-19 oxygen would be absent, as the voluminous TBDMS group is oriented anti to the C10-C5 bond, i.e. away from the double bond.
14. The TBDMS protecting group adds additional steric hindrance to any attack from the β-face.
15. Spontaneous cyclization of the epoxide mixture to give 5 and 6 was also observed on standing, after several days at room temperature.
16. Haasnoot, C. A. G.; de Leew, F. A. A. M.; Altona, C. Tetrahedron 1980, 36, 2783.
17. Wong, T. C.; Rutar, V. J. Am. Chem. Soc. 1984, 106, 7380.
18. Brachet-Cota, A. L. and Burton, G. Z. Naturforsch. 1990, 45b, 711.