Structure and Synthesis of Vindolicine and Derivatives

Abstract

AbstractThis article describes the reaction of vindoline with formaldehyde and trimethyl orthoformate to prepare vindolicine, tris‐vindolicinyl methane and higher molecular weight homologues. The synthesis of 10‐formyl vindoline as an intermediate allowed further exploration of its chemistry, in particular the reaction with acetone which yielded a symmetrical dimer, which was further reacted with vindoline to give molecules containing three and four vindoline units. These molecules were characterized by NMR and for some of them (vindolicine, 10‐formyl vindoline, 10‐(1’‐(but‐1’‐en‐3’‐one))‐vindoline) by X‐ray crystallography. Depending on the substitution and on the absence of axes of symmetry, the NMR spectra displayed non‐equivalent spin systems for the vindoline moieties. The dimer formed from the double condensation of 10‐formyl vindoline with acetone showed cytotoxic activity in the micromolar range.