Total Synthesis Establishes the Biosynthetic Pathway to the Naphterpin and Marinone Natural Products

Abstract

The naphterpins and marinones are naphthoquinone meroterpenoids with an unusual aromatic oxidation pattern that is biosynthesized from 1,3,6,8‐tetrahydroxynaphthalene (THN). We propose that cryptic halogenation of THN derivatives by vanadium‐dependent chloroperoxidase (VCPO) enzymes is key to this biosynthetic pathway, despite the absence of chlorine in these natural products. This speculation inspired a total synthesis to mimic the naphterpin/marinone biosynthetic pathway. In validation of this biogenetic hypothesis, two VCPOs were discovered that interconvert several of the proposed biosynthetic intermediates.

Asymmetric Alkene and Arene Halofunctionalization Reactions in Meroterpenoid Biosynthesis

“…Recently, the George lab completed a simple, biomimetic synthesis of (±)-7-demethylnaphterpin 29 following this biosynthetic proposal. 29 We are now actively working to-gether to interrogate the naphterpin and marinone biosynthetic systems to explore if VHPOs are indeed central to their biosyntheses and, if so, how many are involved in making the putative Diels–Alder substrate.…”