TECHNICAL-SCALE HOMOLOGATION OF A CHOLANIC ACID-DERIVATIVE THROUGH THE BARTON ESTER - A PRACTICAL APPROACH TO 25-HYDROXY VITAMIN-D-3 AND CONGENERS

A novel method was developed of the homologation of a cholanic acid de rivative using the Barton ester, as a practical approach to 25-hydroxy vitamin D and congeners. The method involves transformation of a chol anic acid derivative into a nor-bromide by using 2-mercaptopyridine N- oxide sodium salt and bromotrichloromethane and then alkylation of the bromide,vith dimethylmalonate followed by demethoxycarbonylation by K rapcho procedure. The major byproducts of the synthesis were isolated, and their structures were identified by spectroscopic and chemical me thods. Our method is designed especially for the large scale manufactu ring of vitamin D compounds because it involves an intermediate that c an be easily purified and it avoids the use of toxic and explosive dia zomethane that is employed in the classical synthesis of vitamins D fr om natural steroids.