A New Synthetic Approach to High-Purity (15R)-Latanoprost

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 (15S)-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 & Co. KGaA, 69451 Weinheim, Germany, 2007)