Preparation of bile acids and intermediates thereof
Synthetic methods for preparing deoxycholic acid and intermediates thereof are provided.
1. A method for preparing deoxycholic acid (DCA) or a pharmaceutically acceptable salt thereof:
said method comprising
(a) reacting compound 1.3
with a two carbon olefination reagent under olefin forming conditions to form compound 1.5
(b) converting compound 1.5 to a compound of formula 1.6 wherein P is a protecting group
(c) reacting a compound of formula 1.6 with an alkylpropiolate or an alkyl acrylate CH 2 ═CHC(O)OR wherein R is alkyl in the presence of a Lewis acid to form a compound of formula 1.7 wherein P is a protecting group, R is a alkyl, and the dashed line ---- is a single or double bond;
(d) reacting a compound of formula 1.7 with H 2 under hydrogenation conditions to form a compound of formula 1.8 wherein P is a protecting group and R is alkyl
(e) reacting compound of formula 1.8 with an oxidizing agent to form a compound of formula 1.9 wherein P is a protecting group and R is alkyl
(f) reacting a compound of formula 1.9 with H 2 under hydrogenation conditions to form compound of formula 2.0 wherein P is a protecting group and R is alkyl
(g) reacting compound of formula 2.0 with a reducing agent to form a compound of formula 2.1 wherein P is a protecting group and R is alkyl
(h) exposing compound of formula 2.1 to deprotection and hydrolysis conditions to form deoxycholic acid.