Synthesis of 3a,12a-dihydroxy-23a,23b-dihomo-5b-cholan-24-oic acid

Abstract

A novel multi-step synthesis of 3a,12a-dihydroxy-23a,23b-dihomo-5b-cholan-24-oic acid (23a,23b-dihomodeoxycholic acid) (5) has been achieved from methyl 3a,12a-dihydroxy-5b-cholanoate (1). Reduction of compound 1 with LiAlH4 in dry ether gave the corresponding alcohol 2 in 83 % yield. Selective esterification of compound 2 with tosyl chloride in dry piridine at 0–5 ºC for 12 h afforded the 3a,12a-dihydroxy-5b-24-cholanyl tosylate (3) in 64 % yield. The reaction of the tosyl derivative 3 with sodium diethyl malonate gave compound 4 which was first subjected to hydrolysis under basic conditions, followed by decarboxylation under acidic conditions to afford 3a,12a-dihydroxy-5b-23a,23b-dihomocholan-24-oic acid in 84 % yield.

Keywords

• 26-homodeoxycholic aicd
• bile acids