Water-Mediated Synthesis of (E)-3-(1-Methyl-1H-benzo[d]imidazol-5-yl)-N-phenethylacrylamide, a Caffeic Acid Phenethyl Amide Analogue

Abstract

Caffeic acid phenethyl ester (CAPE) is a phenolic natural product with diverse biological activities, notably anticancer properties. However, its ester group is metabolically unstable. The amide derivative, CAPA, offers improved metabolic stability to esterases but still possesses a metabolically liable catechol group. In this work, we describe the synthesis of a novel CAPA analogue in which the catechol is replaced with a benzimidazole bioisostere via a water-mediated Wittig reaction.