A unified strategy to prostaglandins: chemoenzymatic total synthesis of cloprostenol, bimatoprost, PGF, fluprostenol, and travoprost guided by biocatalytic retrosynthesis.

Development of efficient and stereoselective synthesis of prostaglandins (PGs) is of utmost importance, owing to their valuable medicinal applications and unique chemical structures. We report here a unified synthesis of PGs cloprostenol, bimatoprost, PGF, fluprostenol, and travoprost from the readily available dichloro-containing bicyclic ketone guided by biocatalytic retrosynthesis, in 11-12 steps with 3.8-8.4% overall yields. An unprecedented Baeyer-Villiger monooxygenase (BVMO)-catalyzed stereoselective oxidation of (99% ee), and a ketoreductase (KRED)-catalyzed diastereoselective reduction of enones (87 : 13 to 99 : 1 dr) were utilized in combination for the first time to set the critical stereochemical configurations under mild conditions. Another key transformation was the copper(ii)-catalyzed regioselective -phenylbenzoylation of the secondary alcohol of diol (9.3 : 1 rr). This study not only provides an alternative route to the highly stereoselective synthesis of PGs, but also showcases the usefulness and great potential of biocatalysis in construction of complex molecules.