Synthesis of 21-hydroxycholesterol and 25-hydroxycholesterol from 3β-hydroxyandrost-5-en-17-one. A method for the stereospecific construction of sterol side-chains

Abstract

Alkylation of lithium derivatives of the ethyl and methyl esters of 3β-tetrahydropyran-2-yloxypregn-5-en-21-oic acid (3a) and (3c) with 1-bromo-4-methylpentane gave corresponding derivatives of cholest-5-en-21-oic acid, which were converted into 21-hydroxycholesterol (5e) by reduction of the alkoxycarbonyl groups and acid hydrolysis of the ether group. Alkylation of lithium derivatives of esters (3a) and (3c) with 2-(3-bromopropyl)-2-methyl-1,3-dioxolan (8) followed by conversion of the alkoxycarbonyl groups into a methyl group and removal of the protecting groups gave 3β-hydroxy-27-norcholest-5-en-25-one (7a) which was converted into 25-hydroxycholesterol (7c). Alkylation of the lithium derivative of the ester (3c) with methyl iodide gave methyl (20R)-3β-hydroxy-24,25-bisnorchol-5-en-22-oate (4b).