PREPARATION OF 17ALPHA-PROPADIENYL STEROIDS

摘要

1304395 17α-Propadienyls teroids . SYNTEX CORP 14 April 1970 [18 April 1969] 17731/70 Heading C2U A 17α-propadienyl steroid of the estrane or androstane series is prepared by reacting a 17α-(3-halopropynyl) steroid with a metal of oxidation potential from +0À74 to +2À37 volts inclusive, or with a chromium salt, or with a zinc-copper couple, in the presence of a proton donor. Novel products have the formula wherein R1 is H or C 1-3 alkyl, R2 is H, tetrahydrofuran-2-yl, tetrahydropyran-2-yl or carboxylic acyl, R3 is oxo or α-H(#-OR6) in which R6 is H, tetrahydropyran-2-yl, tetrahydrofuran- 2-yl or carboxylic acyl, and R4 is H or CH 3 . In the products of the process a 3-oxo group may be reduced to a 3#-hydroxy group and this may be converted to a tetrahydropyranyl or tetrahydrofuranyl ether or an acylate. 17α-(3-Halopropynyl)-steroid starting materials are prepared by halogenation of the corresponding 17α-( 3-hydroxypropynyl ) -steroids followed, when required, by hydrolysis of an etherified 17#-OH group to the free OH group and aylation of this. 3 - Ethoxy - 17α - (3 - tetra hydropyran - 21- yloxypropynyl) - 17# - acetoxyestra - 3,5 - diene is prepared from estr-4-ene-3,17-dione via 3- ethoxyestra - 3,5 - dien - 17 - one. 3 - Methoxy- 17α - (3 - hydroxypropynyl) - 17# - tetrahydropyran - 21- yloxyestra - 1,3, 5(10)- triene is prepared from 3-methoxy-17α-ethynylestra-1,3,5- (10)-trien-17#-ol tetrahydropyranyl ether (from the free 17# ol). 6,6 - Difluoro - ester - 4 - ene - 3,17 - dione is prepared from estr-4-ene-3,17-dione via 3- ethoxy - estra - 3,5 - dien - 17 - one, 6α - fluoro. estr - 4 - ene - 3,17 - dione and 3 - ethoxy - 6- fluoroestra - 3,5 - dien - 17 - one. 18 - Homologues of the 6,6 - difluoro compound, and corresponding androstenes, are prepared similarly. All these products are reduced to the corresponding 3#, 17#- diols, these are acetylated to give both the possible mono-acetates and the diacetates, the 3-acetoxy-17-ols are oxidized to the 3-acetoxy- 17-ones, and these are converted to products such as 3#, 1 7# diacetoxy - 6,6 - difluoro - 17α- (3 - hydroxypropynyl)estr - 4 - ene; other 3#,17#- diacylates are prepared similarly. Also, the 3#,17#-diols are etherfied to give both the possible mono-ethers (tetrahydropyranyl or tetrahydrofuranyl ethers) and the diethers, the 3-ether-17#- ols are oxidized to the 17-ones, and these are converted to products such as 3#-tetrahydropyran-21-yloxy - 6,6 - difluoro - 17α - ethynylestr- 4-en-17#-ol and these to the corresponding 17α- (3-hydroxypropynyl) compounds. Similarly prepared are 3#-acetoxy-6,6-difluoro-17α-ethynyl- 17# - tetrahydropyran - 21 - yloxyestr - 4 - ene and the corresponding tetrahydrofuranyl ether via 3# - acetoxy - 6,6 - difluoro - 17α - ethynylestr- 4-en-17#-ol. The novel steroids are stated to possess progestational and pituitary-inhibiting activity. They may be made up into pharmaceutical compositions with suitable carriers.