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

Angew Chem Int Ed Engl. 2018 Aug 20;57(34):11009-11014. doi: 10.1002/anie.201804351. Epub 2018 Jul 23.

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.

Keywords: biomimetic synthesis; biosynthesis; dearomatization; meroterpenoids; total synthesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Biomimetics
  • Chloride Peroxidase / metabolism
  • Cyclization
  • Halogenation
  • Naphthols / chemistry
  • Naphthols / metabolism
  • Naphthoquinones / chemistry
  • Naphthoquinones / metabolism*
  • Oxidation-Reduction
  • Reproducibility of Results
  • Terpenes / chemistry
  • Terpenes / metabolism*

Substances

  • 1,3,6,8-tetrahydroxynaphthalene
  • Biological Products
  • Naphthols
  • Naphthoquinones
  • Terpenes
  • vanadium chloroperoxidase
  • Chloride Peroxidase