Organocatalytic asymmetric Mannich cyclization of hydroxylactams with acetals: total syntheses of (-)-epilupinine, (-)-tashiromine, and (-)-trachelanthamidine

Angew Chem Int Ed Engl. 2014 Nov 24;53(48):13196-200. doi: 10.1002/anie.201407185. Epub 2014 Sep 26.

Abstract

An asymmetric, organocatalytic, one-pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89% yield and 97% ee. The total syntheses of (-)-epilupinine, (-)-tashiromine, and (-)-trachelanthamidine also achieved to demonstrate the generality of the process.

Keywords: acetals; alkaloids; cyclization; natural products; organocatalysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetals
  • Catalysis
  • Cyclization
  • Indolizines / chemical synthesis*
  • Molecular Structure
  • Pyrrolizidine Alkaloids / chemical synthesis*
  • Sparteine / analogs & derivatives*
  • Sparteine / chemical synthesis
  • Stereoisomerism

Substances

  • Acetals
  • Indolizines
  • Pyrrolizidine Alkaloids
  • tashiromine
  • Sparteine
  • lupinine
  • trachelanthamidine