Synthesis of (+)-calanolide A, an anti-HIV agent, via enzyme-catalyzed resolution of the aldol products

Article abstract of DOI:10.1016/0957-4166(96)00433-8

The synthesis of (+)-calanolide A (1), an anti-HIV-1 agent, is described. A TiCl₄-mediated aldol reaction of compound 2 stereoselectively produced the desired syn diastereomer (±)-5, which was resolved by a lipase-catalyzed acylation reaction. Under Mitsunobu conditions (Ph₃P/DEAD), the syn aldol product (+)-5 led to the formation of trans-2,3-dimethyl chroman-4-one [(+)-3] with 94% ee, while the anti aldol product (+)-6 yielded both trans and cis derivatives (+)-3 and (+)-4 with 60% and 68% ee, respectively. Luche reduction on (+)-3 led to (+)-1 and (+)-calanolide B in a ratio of 9:1. Copyright (C) Elsevier Science Ltd.