Chemoenzymatic synthesis of all four cytoxazone stereoisomers

Racemic cytoxazone (+/- -5) was synthesized starting from easily available glycidic ester (+/-)-1 by nucleophilic epoxide ring opening, followed by 2- oxazolidinone ring construction and calcium chloride/sodium borohydride red uction of the intermediary ester (+/-)-4. Kinetic resolution of (+/-)-5 per formed by acetylation with vinyl acetate catalyzed by Penicillium camembert i lipase (PcamL) afforded, on hydrolysis of acetate (-)-6, cytoxazone (-)-5 in 33% overall yield and 88.2% enantiomeric excess (ee), and its enantiome r (+)-5 (38% yield, 89.3% ee). Base-catalyzed epimerization of intermediary (+/-)-4 to (+/-)-7, and reduction and kinetic resolution with Candida anta rctica lipase (CAL) led to epi-cytoxazones (-)-8 and (+)-8.