Convergent Synthesis of Antitumor Aplysiatoxin Derivatives Based on a Combination of Ring-closing and Cross Metathesis

Abstract

We investigated a convergent synthesis of aplysiatoxin analogs based on a combination of ring-closing and cross metathesis. The route provided four analogs (3a–d) with different side chains to determine the CH/π interaction with protein kinase C (PKC)-C1 domains. Biochemical evaluation revealed that a naphthol moiety did not improve binding to PKC-C1 domains, suggesting that the hydrogen bonding of the hydroxy group with the PKC-C1 domains may be more important than the CH/π interaction.