A new chemoenzymatic approach to the synthesis of Latanoprost and Bimatoprost

•New enzymatic steps in the synthesis of Latanoprost and Bimatoprost are developed.•Synthesis can be addressed modulating kind and concentration of cosubstrate.•P. anomala proved to be a source of new synthetically useful and selective enzymes.

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 (CC reduction, stereoselective CO 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, CC 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.

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