Further structure-activity-relationship studies on A/C/D-ring analogs of complement inhibitor K-76

A series of new A/C/D-ring analogs (4a-f, 15) of fungal metabolite K-76 (1a) have been synthesized and evaluated for human complement inhibitory potency. The in vitro assay results of human complement-mediated hemolysis of A/C/D-ring analogs indicate that the carboxylic acid functionality at C-6 is more important than C-7. The presence of aldehydic group and the terpenoid diol in these analogs contribute little towards human complement inhibition. The role of the phenolic hydroxyl is critical as benzofurans 4a and 4b exhibit human complement inhibition similar to the natural product.