Asymmetric total synthesis of (+)-luciduline: toward a general approach to related Lycopodium alkaloids

J Org Chem. 2011 Jul 1;76(13):5354-62. doi: 10.1021/jo200745n. Epub 2011 Jun 1.

Abstract

As part of a research program directed toward the synthesis of Lycopodium alkaloids, a multigram scale asymmetric synthesis of intermediate 11 was achieved in 11 steps from pyridine (17). In addition to our alkene metathesis strategy, a key feature of this synthetic approach consists of a Fukuyama's Diels-Alder cycloaddition between 1,2-dihydropyridine and acrolein using MacMillan's catalyst (18) on a 50 g scale. This led to a 12-step catalytic asymmetric synthesis of (+)-luciduline (1). A broader subset of Lycopodium alkaloids could also be obtained, as demonstrated by the derivatization of 11 into advanced intermediates for the synthesis of some of these natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Lycopodium / chemistry*
  • Molecular Structure
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Stereoisomerism

Substances

  • Alkaloids
  • Quinolines
  • luciduline