| abstract |
A method of preparing (~)-calanolide A, (1), a potent HIV reverse transcriptase inhibitor, from chromene (4) is provided. Useful intermediates for preparing (~)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene (4) intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone (7). Reduction of chromamone (7) with sodium borohydride, in the presence of cerium trichloride, produced (~) (~)-calanolide A. A method for resolving (~)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for heating or preventing viral infections using (~)-calanolide or (-)-calanolide is provided. |