GB846909A - Steroid compounds - Google Patents

Abstract

The invention comprises pregnudienes of the general formula:- <FORM:0846909/IV(b)/1> wherein R represents hydrogen or an acyl radical, X represents halogen and Y represents a hydroxy or keto radical, and the preparation thereof by treating the corresponding D 4-compound with the dehydrogenating activity obtainable in a medium fermented by microorganisms of the species Bacillus sphaericus to produce a compound of the above general formula in which R represents hydrogen, and, when required, acylating the product at the 21-position to produce a compound in which R represents an acyl radical. The radical R preferably represents a C1-6 alkanoyl radical (particularly the acetyl or propionyl radical) or the benzoyl radical. X preferably represents chlorine or fluorine. A number of suitable reactants are detailed below. The micro-organism is preferably B. sphaericus ATCC No. 12488, 7055, 7054 or 245. In the examples the following compounds are prepared :- 12a -fluoro-D 1,4-3,20-diket-11b , 21-dihydroxy-pregnadiene and 12a -fluoro-D 1,4-3,11,20-triketo-21-hydroxy-pregnadiene and the acetates thereof, 12a -chloro-D 1,4-pregnadiene-11b , 21-diol-3,20-done and 12a -chloro-D 1,4-prepnadiene-21-ol-3,11,20-trione. 12a -Halo-D 4-3,20-diketo-11, 12-bis-oxygenated-pregnenes of the general formula:- <FORM:0846909/IV(b)/2> wherein R, X and Y have the above significance, are prepared by reacting 12a -bromo-D 4-3,11, 20-triketo-21-hydroxy-pregnene with an excess of semicarbazide to form 12a -bromo-D 4-3,11,20-triketo-21-hydroxy-pregnene 3,20-bis-semicarbazone, reducing the bis-semicarbazone with lithium borohydride to form 12a -bromo-D 4-3,20-diketo-11b , 21-dihydroxy-pregnene 3, 20-bis-semicarbazone and hydrolysing this compound to form 12a -bromo-D 4-3, 20-diketo-11b , 21-dihydroxy-pregnene. This 12a -bromo compound may be converted into other corresponding 12a -halo derivatives by reacting the 12a -bromo-compound with a base to produce D 4-3,20-diketo-11b ,12a -oxido-21-hydroxy-pregnene, reacting this compound with an acylating agent, e.g., a lower alkanoic anhydride such as acetic anhydride, to form D 4-3,20-diketo-11b ,12a -oxido-21-acyloxy-pregnene, and reacting this compound with a hydrohalic acid, e.g. hydrofluoric or hydrochloric acid to form a 12a -halo-D 4-3,20-diketo-11b -hydroxy-21-acyloxy-pregnene and, when required, oxidising the 11b -hydroxy group with chromium trioxide in pyridine to form the corresponding 11-keto compound. The free 21-hydroxy compounds may be obtained by hydrolysing the 21-acyloxy compounds with methanolic potassium hydroxide. Specification 719,226 also is referred to.