SYNTHESIS OF (-CALANOLIDE-A, AN ANTI-HIV AGENT, VIA ENZYME-CATALYZED RESOLUTION OF THE ALDOL PRODUCTS())

The synthesis of (+)-calanolide A (1), an anti-HIV-1 agent, is describ ed. A TiCl4-mediated aldol reaction of compound 2 stereoselectively pr oduced the desired syn diastereomer (+/-)-5, which was resolved by a l ipase-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 produ ct (+)-6 yielded both trans and cis derivatives (+)-3 and (+)-4 with 6 0% and 68% ee, respectively. Luche reduction on (+)-3 led to (+)-1 and (+)-calanolide B in a ratio of 9 : 1. Copyright (C) 1996 Elsevier Sci ence Ltd