A New Synthetic Approach to Prostaglandin Analogues: Synthesis of Bimatoprost via Lipase Enzymatic Catalysis

Abstract

A simple, convenient and efficient synthetic approach for the synthesis of (15S) bimatoprost (4) via lipase enzyme mediated stereo selective reduction from chiral precursor Corey lactone diol as substrate was described. Swern oxidation, lipase enzymatic reduction and Wittig reaction conditions are used as key steps for the synthesis of bimatoprost. This method was found to be an efficient with considerable yield, cost effective and minimized the synthetic steps compared to reported procedures.

Review of the Synthesis of Bimatoprost Drug Substance Used for the Treatment of Open-Angle Glaucoma

“…This one-pot biotransformation gave a good yield of key intermediate 51 with high stereoselectivity and therefore completed formal synthesis of bimatoprost (6). A similar enzymatic approach was reported by Kamadi and co-workers 58 using lipase for the synthesis of 78, a key intermediate of bimatoprost (6, Scheme 13). In this approach, the enone 77, in which the hydroxyl group was protected as triethylsilyl ether (TES), was added to 0.1 M phosphate buffer solution (pH 7− 7.5) followed by CAL-B enzyme to afford 78 on a 31 g scale, which was converted to bimatoprost (6) in three steps.…”

“…Various literature approaches − for the synthesis of bimatoprost ( 6 ) were assessed from a process chemistry perspective, and a comparative summary is provided in Table . This assessment is based on the reported data and attributes that enables selection of a synthetic route for further optimization and manufacture of drug substance such as quality, type of reagents used, purification, scale, safety, etc.…”