A New Synthetic Approach to High‐Purity (15<i>R</i>)‐Latanoprost

Abstract

Abstract This paper describes a new synthesis of latanoprost ( 1 ) that afforded high purity latanoprost in 16.9 % overall yield in eight synthetic steps from sulfone 4 . The “α chain” in a derivative of the (–)‐“Corey lactone” was elongated first, followed by the attachment of a novel, enantiomerically pure “ω chain” synthon. This ensured the absence of the undesired (15 S )‐ 1 diastereomer in the synthesized prostaglandin. The crystalline nature of the novel sulfone 4 facilitated its purification. A variation of the new synthesis of latanoprost is described, where the laboratory‐scale synthesis was further adapted to a hundred‐gram scale. In the course of the present synthesis, a new prostaglandin sulfone intermediate, 21 , which may find application in the synthesis of diverse prostaglandin analogs, was introduced. A practical synthesis of novel, enantiomerically pure “ω chain” synthons 15 , 16 , and 17 has also been carried out, employing diol 12 , which was obtained from derivatives of the D ‐mannitol chiral pool. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)