Facile synthesis of hydroxy wilfordic acid, a esterifying unit of anti-HIV sesquiterpene pyridine alkaloids

Abstract

Sesquiterpene pyridine alkaloids were isolated mainly from plants of the genus Tripterygium (Celastraceae) which have been used traditionally in Chinese medicine. These compounds have polyhydroxy dihydro-beta-agarofuran core and esterifying substituent with dilactone bridges, and recently demonstrated promising anti-HIV activity. We have achieved the synthesis of hydroxy wilfordic acid and its ester via asymmetric cyanosilylation. With a NMR study of (S)- and (R)-PGME (phenylglycine methyl ester) amide, the tertiary alcohol stereochemistry of synthetic hydroxyl wilfordic acids was determined. Our synthetic approach will provide a contribution to the synthesis of sesquiterpene pyridine alkaloids and the development of their analogs for anti-HIV activity.