An Artificial In Vitro Metabolism to Angiopterlactone B Inspired by Traditional Retrosynthesis.

Abstract

Nature's way to construct highly complex molecular entities as part of biosynthetic pathways is unmatched by any chemical synthesis. Yet, relying on a cascade of native enzymatic transformations to achieve a certain target structure, biosynthesis is also significantly limited in its scope. In this work, non-natural biocatalytic modules, a peroxidase-mediated Achmatowicz rearrangement and a dehydrogenase-catalyzed borrowing hydrogen-type isomerization, are successfully implemented into an artificial metabolism, combining the benefits of traditional retrosynthesis with the elegance and efficacy of biosynthetic networks. In a highly streamlined process, the total synthesis of the tricyclic angiopterlactone B is achieved in two steps operating entirely in an aqueous environment while relying mainly on enzymes as key reaction mediators.