A new chemoenzymatic approach to the synthesis of Latanoprost and Bimatoprost

Bimatoprost (1) and Latanoprost (2) are prostaglandin analogues widely used for glaucoma treatment. We have developed a new chemoenzymatic synthesis for 1 and 2, which utilizes a highly stereoselective sequence of biotransformations catalyzed by enzymes belonging to a single microorganism (the yeast Pichia anomala). The original synthesis, starting from (-)-Corey lactone benzoate (3aR,4R,5R,6aS)-3, was modified by replacing three synthetic steps (C=C reduction, stereoselective C=0 reduction and hydrolysis/deprotection of the benzoate ester) with a one-pot, three-enzymes reaction. The overall biotransformation gave good yields and it was highly stereoselective; noteworthy, by engineering the reaction medium, C=C reduction could be modulated so that unsaturated (3aR,4R,5R,6aS,3'S)-6 or saturated intermediate (3aR,4R,5R,6aS,3'R)-7 could be preferentially obtained. (C) 2014 Elsevier B.V. All rights reserved.