SYNTHESIS OF ANTINEOPLASTIC ANALOGS OF APLYSIATOXIN WITH VARIOUS SIDE CHAIN STRUCTURES

摘要

We have recently developed a simplified analog of aplysiatoxin with anti-proliferative activity (1). To investigate the structure-activity relationship of its side chain, an alternative synthetic route of 1 has been established. Via the key intermediate 6, p-hydroxyl or o,m-dihydroxyl derivatives (4 and 5) as well as 1 were synthesized and their biological activities were evaluated. Although the position of the hydroxyl group in the benzene ring did not change the affinity for protein kinase C isozymes or the ability to induce the Epstein-Barr virus early antigen, anti-proliferative activities against several human cancer cell lines of 1 were superior to those of 4.