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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