Delta<,5>-7alpha-Methyl-Estradienes and their preparation

摘要

1,162,769. #3,5-7α-Methyl-estradiene compounds. CIBA Ltd. 30 Oct., 1967 [28 Oct., 1966], No. 49202/67. Heading C2U. Novel steroids of the formula (wherein R 1 is a free, esterified or etherified OH group; and R 2 is a C 1-4 aliphatic hydrocarbon radical which may be halogen-substituted or is hydrogen, or R 1 and R 2 together are an oxo group) are prepared (1) by liberation of a protected 17-oxo group e.g. a ketalized oxo group, to form a free 17-oxo group in appropriate 3-unsubstituted - #3,5 - 7α- methyl starting materials; (2) by splitting off water or acid from corresponding 3 - (free or esterified hydroxy) compounds containing a #4, #5 or #5(10) double bond; (3) by treating with Raney nickel in a solvent corresponding compounds containing a 3-benzylthio substituent; (4) by splitting off water or acid from corresponding 4α-(free or esterified hydroxy) compounds containing a #5 double bond; or (5) by halogenating and dehydrohalogenating corresponding #4 ring B saturated compounds; followed, when desired, by reduction of the 17-one to a 17#-ol with or without introduction of a 17α-hydrocarbon substituent, by oxidation of the 17#-ol to the 17-one, by esterification or etherification of a free 17#-ol, or by liberation of a free 17#-ol from its ether or ester. In method (2) starting materials may be used which, under the reaction conditions, are converted to the stated starting materials containing a #4, #5 or # 5(10) double bond e.g. there may be used starting materials containing a 3-(free or esterified OH group) and a 5- or 6-(free or esterified OH group) and being fully saturated in rings A and B; this variant may be carried out stepwise, by first eliminating the 3-substituent and then the 5- or 6-substituent. Esters which may be used in method (2) include not only arylates such as alkanoates but also carbalkoxylated 3- hydroxy compounds and xanthates containing a 3-O.CS.S alkyl group. #4 - 3,17# - Dihydroxy - 7α- methylestrene is prepared by reduction of 7α-methyl-19-nortestosterone. The #3'5 - 3 - unsubstituted - 7α- methylestradienes of the invention, which are stated to possess estrogenic and antiovulating properties, may be made up into pharmaceutical or veterinary compositions for enteral, parenteral or local administration with suitable carriers.