Calciferol and its relatives. Part VIII. Ring a intermediates for the synthesis of tachysterol3

Abstract

The racemic and optically active forms of 5-hydroxy-2-methylcyclohex-1-enylmethanol, required for the synthesis of tachysterols, have been obtained from the corresponding forms of 5-hydroxy-2-methylcyclohex-1-ene-1-carboxylic acid or its methyl ester. Three routes were found to the racemic acid or its methyl ester. (a) The corresponding methyl ketone was prepared and degraded to the acid with sodium hypobromite. (b) Reaction of the γ-lactone of cis-5-hydroxy-2-methylcyclohex-2-ene-1-carboxylic acid with methanolic sodium methoxide gave the desired methyl ester. (c) The principal keto-acid obtained by addition of 2-ethoxybutadiene to citraconic anhydride, followed by hydrolysis of the products, was shown to be 1-methyl-4-oxocyclohexane-cis-1,2-dicarboxylic acid. Reduction gave cis-4-hydroxy-1-methylcyclohexane-cis-1,2-dicarboxylic acid, which formed both a δ-lactonic acid and a γ-lactonic acid. The latter was degraded in two different ways to the racemic methyl ester of 5-hydroxy-2-methylcyclohex-1-ene-1-carboxylic acid.

The δ-lactonic acid was resolved, and each enantiomer was separately converted into the corresponding form of the γ-lactonic acid, and thence into the corresponding enantiomer of methyl 5-hydroxy-2-methylcyclohex-1-ene-1-carboxylate.