Unified Total Synthesis of Tetracyclic Diquinane Lycopodium Alkaloids (+)-Paniculatine, (-)-Magellanine, and (+)-Magellaninone

J Org Chem. 2022 Jul 1;87(13):8685-8696. doi: 10.1021/acs.joc.2c00871. Epub 2022 Jun 14.

Abstract

A unified route for the total synthesis of three tetracyclic diquinane Lycopodium alkaloids (+)-paniculatine, (-)-magellanine, and (+)-magellaninone has been accomplished in 13-14 overall steps based on late-stage diverse transformations from an advanced tetracyclic common intermediate. In the established synthesis, quick formation of the two five-membered rings was efficiently achieved by an intramolecular reductive coupling of ketone-carbonyl and ester-carbonyl and an organocatalytic intramolecular Michael addition of aldehyde-derived enamine to an internal enone functionality with satisfactory redox and step economies and excellent stereoselectivities, providing the requisite tricyclic carbo-framework possessing multiple dense stereogenic centers, and an intramolecular reductive amination finally furnished the essential piperidine ring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids*
  • Heterocyclic Compounds, 4 or More Rings
  • Lycopodium*
  • Molecular Structure
  • Stereoisomerism

Substances

  • Alkaloids
  • Heterocyclic Compounds, 4 or More Rings
  • magellaninone
  • paniculatine
  • magellanine