Patent GB-963427-A (GB)
Title: 16-methylene-17ª -acetoxy-progesterone-derivatives and the preparation thereof
IPC: C07J75/00
Filed: 1961-01-23
Abstract: 963,427. Steroids. E. MERCK A.G. Jan. 23, 1961 [Jan. 30, 1960], No. 2606/61. Heading C2U. The invention comprises steroids of the general formula: wherein X represents hydrogen, fluorine or chlorine or the methyl group, R represents hydrogen or a hydroxy group (R represents OH when Y represents fluorine), and the corresponding #<SP>1-</SP>, # <SP>6</SP>- and #<SP>1</SP>, <SP>6</SP>-derivatives thereof, and the preparation thereof by treating 16- methylene -17α- acetoxy-progesterones of the general formula: wherein R, X and Y have the above significance, with chloranil to form the corresponding 6- dehydro-compound and/or dehydrogenating at the 1,2-positions by treating with 2,3-dichloro-5, 6-dicyano-benzoquinone, selenium dioxide or 1,2-dehydrogenating microorganisms, by treating a 9#, 11#-oxido compound of the general formula: wherein X has the above significance, or the corresponding 1, 2 and/or 6, 7 unsaturated compound, with hydrogen fluoride, by treating a steroid of the general formula: wherein X has the above significance and R 1  represents hydrogen or acyl and a bromine atom may be attached to C 5  in which case the 5,6-position is saturated if X is fluorine, with a chemical or microbiological oxidising agent such as a mixture of a ketone and an aluminium alcoholate chromic acid, potassium dichromate or N-bromo-succinimide or the oxygenating activity produced by growing Flavobacterium dehydrogenans microorganisms or microorganisms of the genus Aspergillus, Bacillus, Corynebacterium, Ermothecium, Mycobacterium, Penicillium, Phycomyces, Pseudomonas, Steptomyces or Ustilago and by treating steroids of the general formula: wherein X has the above significance, or a corresponding 1,2 and/or 6,7-unsaturated compound, with an acetylating agent. Suitable microorganisms which may be used for 1,2-dehydrogenation are of the genus Alternaria, Didymella, Calonectria, Colletotrichum; Cylindrocarpon, Fusarium, Ophiobolus, Septomyxa, Vermicularia, Acetobacter, Aerobacter, Alcaligenes, Bacillus, Corynebacterium, Erysipelothrix, Fusarium, Listeria, Micromonospora, Mycobacterium, Nocardia, Protaminobacter, Pseudomonas and Steptomyces. Particularly suitable 1,2-dehydrogenating microorganisms are Bacillus sphaericus var. fusiformis, Corynebacterium simplex and Fusarium solani. It is possible to use more than one of the above processes to prepare a steroid of the first general formula above. In addition, a steroid prepared by the last process above may be subsequently 11-hydroxylated, then dehydrated to form the 9,11-dehydro derivative, epoxised to form the 9 #, 11 #-oxido-steroid and then treated with hydrogen fluoride to form the 9α-fluoro-11#-hydroxy-compound. 16-Methylene-steroids of the previous four general formulae above are prepared from the corresponding 16#-methyl-16α, 17α-oxidosteroids by treatment with at least catalytic quantities of a strong acid and may be acetylated as required. Pharmaceutical compositions having progesterone type activity and which may be administered as pills, tablets, dragees, suppositories, emulsions, suspensions or injectable solutions contain as the active ingredient steroid compounds of the first general formula above. Specifications 857,114, 858,033 and 941,553 are referred to.