Preparative Bioorganic Chemistry; 8.1Efficient Enzymatic Preparation of (1R,4S)-(+)-4-Hydroxy-2-cyclopentenyl Acetate

Abstract

An efficient method for the preparation of (1R,4S)-(+)- 4-hydroxy-2-cyclopentenyl acetate, a useful chiral starting material for the synthesis of prostaglandins, is described. A mixture of cis- and trans-3,5-diacetoxycyclopentene, readily obtainable on a preparative laboratory scale, was used as the substrate for the hydrolysis with commercially available pig pancreatic lipase (PPL). PPL hydrolyzed the substrate enantioselectively and substrate-selectively, yielding mainly the (+)-cis-monoacetate and trans-diacetate (Method A). The former was recrystallized to give the diastereomerically and optically pure (+)- cis-monoacetate. Ester exchange of cis/trans mixture of the diacetate in an organic solvent using enzymes as batch or flow system was also investigated (Method B). Method A was applicable to 0.25 mol of substrate, and yielded 0.127 mol (18 g, 51%) of optically pure (+)-monoacetate with recycling recovered materials.