Programmable meroterpene synthesis

Nat Commun. 2020 Jan 24;11(1):508. doi: 10.1038/s41467-020-14354-5.

Abstract

The bicyclo[3.3.1]nonane architecture is a privileged structural motif found in over 1000 natural products with relevance to neurodegenerative disease, bacterial and parasitic infection, and cancer among others. Despite disparate biosynthetic machinery, alkaloid, terpene, and polyketide-producing organisms have all evolved pathways to incorporate this carbocyclic ring system. Natural products of mixed polyketide/terpenoid origins (meroterpenes) are a particularly rich and important source of biologically active bicyclo[3.3.1]nonane-containing molecules. Herein we detail a fully synthetic strategy toward this broad family of targets based on an abiotic annulation/rearrangement strategy resulting in a 10-step total synthesis of garsubellin A, an enhancer of choline acetyltransferase and member of the large family of polycyclic polyprenylated acylphloroglucinols. This work solidifies a strategy for making multiple, diverse meroterpene chemotypes in a programmable assembly process involving a minimal number of chemical transformations.

Publication types

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

MeSH terms

  • Biosynthetic Pathways*
  • Monoterpenes / chemical synthesis
  • Monoterpenes / chemistry
  • Monoterpenes / metabolism*
  • Oxidation-Reduction
  • Stereoisomerism
  • Terpenes / chemical synthesis
  • Terpenes / chemistry

Substances

  • Monoterpenes
  • Terpenes
  • garsubellin A