Synthesis of bile acid analogs: 7-alkylated chenodeoxycholic acids

This paper describes a method for the preparation of 7-alkylated chenodeoxycholic acids from 3 alpha-hydroxy-7-oxo-5 beta-cholanoic acid. The synthetic procedure is based upon a Grignard reaction between the keto bile acid and an alkyl magnesium halide. Under the conditions employed, the introduction of alkyl groups is highly stereoselective. Only 7 beta-alkylated epimers are obtained. The overall yield is several-fold higher than that obtained by the previous method, which involved the preparation of an oxazoline intermediate.