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

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-β-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. © 2009 The Pharmaceutical Society of Korea and Springer Netherlands.