GB736817A - Improvements in or relating to reduction of 3-keto steroids to 3a-hydroxy steroids - Google Patents

Abstract

The invention comprises 5-isostigmast-22-en-3a -ol, the alkyl esters of 3a -hydroxy-D 7-bisnorcholenic acid, e.g. the methyl ester, and a process for reducing the 3-keto group of a 3-keto A/B cis steroid by reaction with lithium aluminium hydride in an anhydrous solvent medium, and hydrolysing the reaction product, e.g. with aqueous hydrochloric acid, to form a 3a -hydroxy A/B cis steroid. The 3-keto A/B cis steroid may contain double bonds in the nucleus, hindered keto groups elsewhere in the steroid nucleus such as in the 11- or 12-position or carboxylic ester groups present in the side chain substituted at C17 as in esters of the bisnorcholanic acid series, e.g. esters of 3-ketobisnorcholanic acid, 3,11-diketo-bisnorcholanic acid and 3-keto-D 7-bisnorcholanic acid such as the methyl esters. If the 3-keto group is the sole unhindered oxo group in the steroid reactant, 1/4 mol. of lithium aluminium hydride is sufficient to carry out the reduction. Additional unhindered reactive keto groups are preferably protected, e.g. by conversion to cyclic ketal groups by reaction with an alkylene glycol. The process may be used to prepare pregnan-3a -ol-20-one from pregnan-3,20-dione through the intermediate 20-ethylene ketal, etiocholan-3a -ol-17-one from etiocholandione-3,17 through the intermediate 17-ethylene ketal, coproergost-22-en - 3a - ol from coproergostenone, 5 - isostigmast - 22 - en - 3a - ol from 5 - isostigmast-22 - en - 3 - one, methyl 3a - hydroxy - bisnorcholanate from methyl-3-keto-bisnorcholanate, methyl - 3a - hydroxy - D 7 - bisnorcholenate from methyl - 3 - keto - D 7 - bisnorcholenate, and methyl - 3a - hydroxy - 11 - keto - bisnorcholanate from methyl - 3,11 - diketo - bisnorcholanate. The examples refer in detail to the preparation of the compounds referred to above, and, in addition, refer to the following compounds: 5 - isostigmast - 22 - en - 3a - ol acetate (obtained from the corresponding 3a -hydroxy compound by reaction with acetic anhydride), 3a - acetoxybisnorcholanic acid (obtained by hydrolysing the corresponding methyl ester with potassium hydroxide. Esters other than the methyl ester of the bisnorcholanic acid series may be used in the above process, e.g. the propyl, isobutyl, benzyl and naphthyl esters may be used. Esters of other side chain steroid acids are also suitable, e.g. the esters of cholanic, norcholanic and etiocholanic acids. Specification 736,818 is referred to.