Total Synthesis of Matrine Alkaloids

J Am Chem Soc. 2022 Nov 2;144(43):19695-19699. doi: 10.1021/jacs.2c09804. Epub 2022 Oct 19.

Abstract

The total synthesis of three diastereomeric matrine natural products is reported. The 8-step synthesis commences with simple acyclic precursors, forms all 4 rings of the tetracyclic natural product framework, and forges 10 of the 20 covalent bonds of the target structure. A cross-conjugated triene is positioned at the core of an acyclic branched structure. This precursor collapses to the tetracyclic natural product framework through an orchestrated sequence of two separate intramolecular cycloadditions. A subsequent, late-stage hydrogenation is accompanied by strain-release redox epimerizations to deliver the three natural products. An unprecedented carba-analogue is prepared in the same way. Semisynthetic manipulations of matrine provide access to 10 additional natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids* / chemistry
  • Biological Products*
  • Matrines
  • Molecular Structure
  • Quinolizines

Substances

  • Quinolizines
  • Alkaloids
  • Biological Products
  • Matrines