GB827556A - New cyclopentanophenanthrene derivatives and process for the production thereof - Google Patents

Abstract

The invention comprises 6-alkyl steroids of the general formula <FORM:0827556/IV (b)/1> and the corresponding D 1,4-pregnadienes (R1 is alkyl of from one to six carbons, R is hydrogen or a hydrocarbon carboxylic ester residue of less than twelve carbons, and X is a keto or b hydroxy group) together with their preparation by treating the 3,20-bis-ethylene ketal of a D 4 - 3,20 - diketo - 17,21 - dihydroxy - 11 - oxygenated pregnene with an aromatic peracid to form the corresponding 5a ,6a -oxido compound, reacting this compound with an alkyl magnesium bromide to form a 5a -hydroxy-6a -alkyl derivative, subjecting said derivative to hydrolysis, dehydration and rearrangement at C6 to form the corresponding D 4-6-alkyl compound and if necessary dehydrogenating with selenium dioxide in the presence of t-butanol and acetic acid to the D 1,4-6-alkyl analogue. Hydrolysis, dehydration and rearrangement are normally effected by treatment with mineral acids, e.g. dilute H2SO4 in ethanol, the dehydration being completed by treatment with a base, e.g. methanolic KOH, under nitrogen and the mixture then re-acidified. Specified 21-ester groups are acetate, trimethylacetate, propionate, cyclopentylpropionate, butyrate, and benzoate. In examples: (1) the 3,20-bisethylene ketal of cortisone 21-acetate is treated with perbenzoic acid in chloroform, the resulting 5a ,6a -epoxide reacted with methyl magnesium bromide giving 6b -methyl-pregnane3,20 - bis - cycloethylenedioxy - 5a ,17a ,21 - triol11-one, which is refluxed with aqueous-ethanolic H2SO4, the product evaporated to dryness, treated with methanolic KOH under nitrogen and then acidified to give 6a -methyl-cortisone; (2) 6a -methyl-hydrocortisone is likewise prepared; and (3) to (5), these compounds are esterified to the corresponding 21-acetates, trimethylacetates, propionates and butyrates; (6) 6a -methylcortisone 21-acetate is refluxed under nitrogen with SeO2 in t-butanol and acetic acid giving 6a -methyl-1-dehydrocortisone 21-acetate; (7) 6a -methyl-1-dehydro-hydrocortisone 21-acetate is likewise prepared; and (8) and (9), these compounds are saponified to the free 21-ols; and (10) re-esterified to the corresponding 21-trimethylacetates, propionates and butyrates.