A new chemoenzymatic synthesis of d-cloprostenol

A new chemoenzymatic synthesis of d-cloprostenol based on the biocatalytical resolution of anti-2-oxotricyclo[2.2.1.0]heptan-7-carboxylic acid 1 has been developed. The resolution was attempted by different approaches: esterification or reduction of the acid and hydrolysis or reduction of the corresponding esters. The most efficient method proved to be the reduction of the propyl esters of 1 catalysed by the yeast Kluyveromyces marxianus, which allowed for the recovery of the enantiomerically pure ester of anti-2-oxotricyclo[2.2.1.0]heptan-(R)-7-carboxylic acid (R)-3 at 60% molar conversion of 3.0 g/l of racemic substrate acid under optimised conditions. anti-2-Oxotricyclo[2.2.1.0]heptan-(R)-7-carboxylic acid was obtained by alkaline hydrolysis and employed for the synthesis of d-cloprostenol.

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anti-2-Oxotricyclo[2.2.1.0]heptan-(R)-7-carboxylic acidC8H8O3[α]D25=+93.0 (c 1.0, MeOH)

Propyl anti-2-oxotricyclo[2.2.1.0]heptan-(R)-7-carboxylateC11H14O3[α]D25=+23.1 (c 1.0, MeOH)