GB841870A - Improvements in or relating to 6-methyl steroids - Google Patents

Abstract

The invention comprises 6-methyl-25D-spirost-5-en-3 b -ol and the 3b -acyloxy derivatives thereof; 6 - methylandrost - 5 - ene - 3b :17b - diol; 17 a - ethynyl - 6 - methylandrost - 5 - ene - 3b : 17b - diol; 17b - acetoxy - 6#x - methyl - 3:5-cycloandrostan-6#x-ol; 17 a -ethynyl-6#x-methyl-3:5-cycloandrostane-6#x:17b -dioland 6#x-hydroxyl-6#x - methyl - 3:5 - cyclopregnan - 20 - one; and a method for the preparation of a 3b - hydroxy - 6 - methyl - D 5 - steroid of the androstane, pregnane or spirostane series by oxidizing the corresponding 6b -hydroxy- or 6b -acyloxy-3:5-cyclo-steroid to a 6-oxo-3:5-cyclo-steroid, treating this with a methyl organometallic reagent to give a 6#x-hydroxy-6#x-methyl-3:5-cyclosteroid and rearranging this with an acid. The oxidation of the 6b -hydroxy-steroid is advantageously effected with chromium trioxide, sodium dichromate, N-bromoacetamide or pyridine/chromic acid, while the 6b -acyloxysteroid may be directly oxidized with chromic acid. Grignard reagents are the preferred organometallic reagents, and the rearrangement may be effected either by treatment with a source of hydrogen ions e.g. sulphuric acid, in an aliphatic acid containing at most 5 carbon atoms to give the 3b -acyloxy-6-methyl- D 5-steroid which is subsequently hydrolysed with aqueous ethanolic alkali, or by use of the source of hydrogen ions in an aqueous organic solvent to give the 3b -hydroxy compound direct. The 3b -acetoxy compounds may alternatively be obtained by the use of a Lewis acid such as boron trifluoride in acetics-anhydride. Primary or secondary hydroxyl groups are protected prior to the oxidation stage e.g. by acylation, and oxo groups are protected by ketal formation or reduction, with subsequent regeneration. In examples (1) 3b -hydroxy-25D-spirost-5-ene and toluene-p-sulphonic acid in pyridine give 3b -toluene-p-sulphonyloxy-25D-spirost-5-ene, this is refluxed with potassuim acetate in water to give 3:5-cyclo-25D-spirostan-6b -ol and this is treated according to the process of the invention to give successively, the 6-one, the 6#x-methyl-6#x-ol, 3b -acetoxy-6-methyl-25D-spirost-5-ene and, finally, the corresponding 3b -ol; (2) 6b :17b -diacetoxy-3:5-cycloandrostane gives by the process of the invention, the 6-one, the 6#x-methyl-6#x-ol (after acetylation of the initially obtained 17b -ol), 3b -17b - diacetoxy - 6 - methylandrost 5-ene and finally the corresponding 3b :17b -diol; (3) 3:5 - cyclo - 17a - ethynyl - androstane - 6b -17b - diol gives, by the process of the invention, the 6-one (2:4 - dinitrophenylhydrazone described), the 6#x-methyl-6#x-ol, 3b -acetoxy-17 a - ethynyl - 6 - methylandrost - 5 - ene-17b -ol and, finally, the corresponding 3b -ol; and (4) 6b -hydroxy-3:5-cyclopregnan-20-one is reduced and acetylated to give 6b :20#x-diacetoxy-3:5-cyclopregnane, this is oxidized, the product converted to its semicarbazone and then decomposed with pyruvic acid and acetic acid to give 20#x-acetoxy-3:5-cyclopregnan-6-one, this with a Grignard reagent gives 6#x-methyl-3:5-cyclopregnane-6#x:20#x-diol, this is oxidized to the corresponding 20-one and this is treated according to the last stage of the process of the invention to give 3b -acetoxy-6-methylpregn-5-en-20-one In the Provisional Specification reference is also made to other 17 a -alkynyl-17b -hydroxy3:5-cycloandrostan-6b -ols and their conversion to the corresponding 17 a -alkynyl-6-methyl-androst-5-ene-3b :17b -diols by the process of the invention.