Steroidal 1,4-Dienes

摘要

1,192,061. #1'4 - 3 - Unsubstituted steroids. AMERICAN HOME PRODUCTS CORP. 24 April, 1967 [25 April, 1966; 13 March, 1967], No. 18663/67. Heading C2U. Novel compounds of formula (wherein R is C 1-5 alkyl; R1, R2 and R3 are H or C 1-5 alkyl; and X is an organic radical of at least 11 carbon atoms so arranged as to complete a cyclopentanoperhydrophenanthrene nucleus) are prepared by reducing the corresponding 3-hydroxy, 3-acyloxy or 3-oxo steroids, any sensitive groups in the molecule having been protected and being subsequently regenerated if required. The 3-hydroxy and 3-acyloxy compounds are reduced with an alkali or alkaline earth metal in liquid ammonia or a liquid amine. The 3-oxo compounds are reduced by reaction with aluminium hydride at 10-30‹ C. to give a mixture comprising the desired product with 1,3- and 2,4-dienes, treating this mixture with lithium in liquid ammonia to reduce these by-products to monoenes, and recovering the desired product from the resulting mixture by crystallization. The *3-Hydroxy-#1.4-steroid starting compounds (some of which are claimed in Specification 1,192,062) are prepared by reduction of the corresponding #1'4-3-ones, and may be converted to the #1,4-3-acyloxy starting materials. 20# - Hydroxypregna - 1,4 - dien - 3 - one is prepared from pregna-1,4-diene-3,20-dione with NaBH 4 . 21 - Acetoxy - 9α - fluoro - 6α - methyl - 11#, 17α - dihydroxy - pregna - 1,4 - diene - 3,20 - dione 20-ethylene ketal is prepared from the corresponding 11-one with NaBH 4 . 11#,20 - Dihydroxy - 17α,21 - isopropylidenedioxy - 1,4 - pregnadien - 3 - one is prepared from the corresponding 3,20-dione with NaBH 4 . Compounds of the above formula are described as having progestational, ovulationinhibiting, anabolic, androgenic, anti-androgenic, anti-inflammatory, anti-estrogenic, low catabolic, glycogenic, thymolytic and antigonadotrophic activities, and may be made up with carriers into pharmaceutical compositions for oral or parenteral administration.