A new chemoenzymatic approach to the synthesis of Latanoprost and Bimatoprost

Abstract 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 (3a R ,4 R ,5 R ,6a S )- 3 , was modified by replacing three synthetic steps (C C reduction, stereoselective C O 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 (3a R ,4 R ,5 R ,6a S ,3′ S ) -6 or saturated intermediate (3a R ,4 R ,5 R ,6a S ,3′ R ) -7 could be preferentially obtained.