Synthesis of (+)‐Calanolide A, an anti‐HIV Agent, via Enzyme‐Catalyzed Resolution of the Aldol Products.

Abstract The synthesis of (+)-calanolide A ( 1 ), an anti-HIV-1 agent, is described. A TiCl 4 -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 (Ph 3 P/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.