A Facile and Efficient Synthesis of (15R)-Latanoprost from Chiral Precursor Corey Lactone Diol

Abstract

An efficient asymmetric synthetic route for the synthesis of anti-glaucoma agent, (15R)-latanoprost using Corey lactone diol as chiral substrate under Swern oxidation, allylic reduction and Wittig reaction conditions has been developed. In this method, reduction of keto and alkene functional groups has been achieved in a single step using low cost catalyst NiCl 2 /NaBH 4 in methanol. This new synthetic protocol is a good alternative for the synthesis of latanoprost with high stereo selectivity and improved yield.

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

“…The crude compound 6 was resulted as a liquid (160 g) after solvent removal under reduced pressure. The spectroscopic data of compound 6 matches with the spectral data reported in our previous paper [12].…”

“…The crude compound was chromatographed on silica gel using ethyl acetate and hexane mixture (50:50) to give compound 7 as a liquid (72 g). 1 H NMR, 13 C NMR spectra of compound 7 matches with the spectral data reported in previous paper [12].…”

“…First, 4-phenylbutan-2-one (5) was transformed into 1-bromo-4-phenylbutan-2-one (6) by treating with bromine in acetic acid. Subsequently, compound 6 were directly converted to corresponding organophosphorus ylide without transforming it into iodo derivate as reported in our previous paper [12]. Further, we have developed an alternative synthetic route for the synthesis of compound 7, from an iodo derivative of 4-phenylbutan-2-one (5) with an improved yield.…”

“…Synthesis: Compound 11 was prepared as reported previously [12] from triethyl silyl protected (-)-Corey lactone diol by employing well established Swern oxidation and Wittig-Horner synthetic protocols.…”

“…In continuation of our research programme to synthesis of biologically potent prostaglandins [12], we report herein an efficient, cost effective synthetic approach for the synthesis of primary prostaglandins, particulary (15S) bimatoprost (4) via lipase enzyme mediated stereo-selective reduction from chiral precursor Corey lactone diol. This method was found to be an efficient with considerable yield, cost effective and minimized the synthetic steps compared to reported procedures.…”