HIV-INHIBITORY NATURAL-PRODUCTS .30. STRUCTURE-ACTIVITY MODIFICATIONSOF THE HIV-1 INHIBITORS (-CALANOLIDE-A AND (-)-CALANOLIDE-B())

The Delta(7,8) olefinic linkages within (+)-calanolide A (1) and (-)-c alanolide B (2) were catalytically reduced to determine impact on the anti-HIV activity of the parent compounds. In addition, a series of st ructure modifications of the C-12 hydroxyl group in (-)-calanolide B w as made to investigate the importance of that substituent to the HIV-1 inhibitory activity of these coumarins. A total of 14 analogs were is olated or prepared and compared to (+)-calanolide A and (-)-calanolide B in the NCI primary anti-HIV assay. While none of the compounds show ed activity superior to the two unmodified leads, some structure-activ ity requirements were apparent from the relative anti-HIV potencies of the various analogs.