Synthesis of obeticholic acid and optimization of the preparation process / 国际药学研究杂志

ABSTRACT

Objective To synthesize obeticholic acid and optimize the preparation process. Method Obeticholic acid was synthesized from (E) -3α-hydroxyl-6-ethylidene-7-keto-5β-cholane-24-acid via the reactions in cluding the double bound hydrogenation, inversion of α-ethyl′s configuration, and stereospecific reduction of the carbonyl group. Results The structures of the compounds were confirmed by1 H NMR, 13 C NMR and MS data. The preparation process was optimized, with the overall yield about 69％.Conclusion An industrial process for the preparation of obeticholic acid has been developed, available for the safety and quality control as well as the quality improvement of final products, which could meet the registration requiremens of Center for Drug Evalution (CDE).