SYNTHESIS, CHROMATOGRAPHIC RESOLUTION, AND ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS ACTIVITY OF (+ -)-CALANOLIDE-A AND ITS ENANTIOMERS/

The anti-HIV agent (+/-)-calanolide A (1) has been synthesized in a fi ve-step approach starting with phloroglucinol [--> 5 --> 6 --> 11 --> 18 --> (+/-)-1], which includes Pechmann reaction, Friedel-Crafts acyl ation, chromenylation with 4,4-dimethoxy-2-methylbutan-2-ol, cyclizati on, and Luche reduction. Cyclization of chromene 11 to chromanone 18 w as achieved by employing either acetaldehyde diethyl acetal or paralde hyde in the presence of trifluoroacetic acid and pyridine or PPTS. Luc he reduction of chromanone 18 at lower temperature preferably yielded (+/-)-1. Reduction of chromone 12, synthesized by Kostanecki-Robinson reaction from chromene 11, failed to afford (+/-)-1. The synthetic (+/ -)-1 has been chromatographically resolved into its optically active f orms, (+)- and (-)-1. The anti-HIV activities for synthetic (+/-)-1, a s well as resultant (+)- and (-)-1, have been determined. Only (+)-1 a ccounted for anti-HIV activity, which was similar to the data reported for the natural product, and (-)-1 was inactive.