Synthesis of l-β-(6-azulenyl)alanine and the fluorescent actin disruptor (6-azuleno)chalasin H

Abstract

L-β-(6-Azulenyl)alanine was synthesised for the first time. Supplementation of this compound to Pyricularia grisea ΔpyiA led to the biosynthesis of the unnatural (6-azuleno)chalasin H and its 1′-bromo congener that have unprecedented natural product skeletons and that are both fluorescent and highly cytotoxic, with IC₅₀ of 0.18 μg mL⁻¹ vs. L929 cells in vitro. Actin staining showed that both compounds are potent, but partially reversible, actin disruptors.