A simple synthesis of gestodene from 18-methyl-4-estren-3,17-dione

Synlett

Volumn , Issue 10, 2004, Pages 1838-1840

  Ferraboschi, Patrizia ^a   Grisenti, Paride ^b   Onofri, Andrea ^a   Prestileo, Paolo ^a  

^a UNIVERSITY OF MILAN   (Italy)

^b Poli Industria Chimica SpA   (Italy)

Author keywords

Drugs; Progestagen; Steroids; Sulfinylation; Sulfoxides

Indexed keywords

18 METHYL 4 ESTREN 3,17 DIONE; ACETAL; CARBON; CARBONYL DERIVATIVE; ESTRANE DERIVATIVE; GESTAGEN; GESTODENE; SULFOXIDE; UNCLASSIFIED DRUG;

ARTICLE; SYNTHESIS;

EID: 4143053588     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2004-829070     Document Type: Article

References (20)

1. Hoppe, G. Advances in Contraception 1987, 3 (2), 159.
2. (a) Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H. DE 2546062, 1975; Chem. Abstr. 1977, 87, 168265.
3. (b) Hofmeister, H.; Annen, K.; Laurent, H.; Petzoldt, K.; Wiechert, R. Arzneim.-Forsch. 1986, 36 (1), 781.
4. Bohlmann, R.; Laurent, H.; Hofmeister, H.; Wiechert, H. DE 3710728, 1987; Chem. Abstr. 1989, 110, 95633.
5. Prendin, R.; Pirovano, S. EP 700926, 1995; Chem. Abstr. 1996, 124, 343797.
6. (a) Kelly, R. W.; Sykes, P. J. J. Chem. Soc. C 1968, 416.
7. (b) Liu, D.; Stuhmiller, L. M.; McMorris, T. C. J. Chem. Soc., Perkin Trans. 1 1988, 2161.
8. 14-derivatives was obtained from the dehydrobromination and it is known that the conversion of the unconjugated ketone to the conjugated one, occurring in course of the acidic removal of 17-ketal, leads to an epimerization at C-14. See: Johnson, W. S.; Johns, W. F. J. Am. Chem. Soc. 1957, 79, 2005.
9. 3: C, 77.38; H, 9.74; O, 12.88. Found: C, 77.45; H, 9.69; O, 12.95.
10. Trost, B. M.; Salzmann, T. N.; Hiroi, K. J. Am. Chem. Soc. 1976, 98, 4887.
11. Sharpless, K. B.; Lauer, R. F.; Teranishi, A. Y. J. Am. Chem. Soc. 1973, 95, 6137.
12. The selenation-dehydroselenation procedure has already been reported for the synthesis of a 15-androstene derivative. See: Reeder, A. Y.; Joannou, G. E. Steroids 1996, 61, 74.
13. Groszek, G.; Kabat, M. M.; Kurek, A.; Masnyk, M.; Wicha, J. Bull. Pol. Acad. Sci., Chem. 1986, 34, 305.
14. Due to the new stereocenters at the C-16 and SO group, four diastereoisomers were obtained, as shown by TLC (toluene-EtOAc 8:2) analysis.
15. +], 371, 370.
16. 3), 3.20 (dd, J = 8.4 and 10 Hz, 0.34 H, CHSO), 3.41 and 3.43 (two overlapped dd, 0.53 H, CHSO), 3.48 (dd, J = 8.4 and 10 Hz, 0.13 H, CHSO), 5.72, 5.73, 5.75 (three m, in a ratio 0.18:0.32:0.50, CH=), 7.27-7.42 (m, 5 H, Ar).
17. 11).
18. +], 341.
19. 2O), 5.46 (m, 0.55 H, CH=), 5.67 (dd, J = 3.5 and 5.6 Hz, 1 H, CH=), 5.90 (dd, J = 2.0 and 6.0 Hz, 0.55 H, CH=), 5.99 (dd, J = 2.0 and 6.0 Hz, 0.45 H, CH=).
20. 2). The other chemical-physical data are in agreement with the reported ones. See: Von Cleve, G.; Frost, E.; Hoyer, G.-A.; Rosenberg, D.; Seeger, A. Arzneim.-Forsch. 1986, 36 (1), 784.