FURTHER STRUCTURE-ACTIVITY-RELATIONSHIP STUDIES ON A C/D-RING ANALOGSOF COMPLEMENT INHIBITOR K-76/

A series of new A/C/D-ring analogs (4a-f, 15) of fungal metabolite K-7 6 (la) have been synthesized and evaluated for human complement inhibi tory potency. The in vitro assay results of human complement-mediated hemolysis of A/C/D-ring analogs indicate that the carboxylic acid func tionality at C-6 is more important than C-7. The presence of aldehydic group and the terpenoid diol in these analogs contribute little towar ds human complement inhibition. The role of the phenolic hydroxyl is c ritical as benzofurans 4a and 4b exhibit human complement inhibition s imilar to the natural product.