Enantioselective total synthesis of quadrigemine C and psycholeine

J Am Chem Soc. 2002 Aug 7;124(31):9008-9. doi: 10.1021/ja0267425.

Abstract

The first total syntheses of higher-order members of the polypyrrolidinoindoline alkaloid family are reported. The synthesis of quadrigemine C (1) and psycholeine (3) begins with synthetic meso-chimonanthine (4), which is synthesized from commercially available oxindole and isatin in 13 steps and 35% overall yield. Double Stille cross coupling of diiodide 7, available in three steps from 4, with vinylstannane 8 produces dibutenanilide 9. Double catalytic asymmetric Heck cyclization of 9 simultaneously installs the two peripheral quaternary stereocenters and desymmetrizes this advanced meso precursor to deliver the chiral, decacyclic intermediate 11 in 62% yield and 90% ee. In two additional steps, 11 is converted to 1, which upon treatment with acid generates 3. The synthesis of quadrigemine C (1), which rigorously confirms its relative and absolute configuration, was executed in 19 linear steps (2% overall yield) from commercially available starting materials.

Publication types

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

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Cyclization
  • Indicators and Reagents
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Molecular Conformation
  • New Caledonia
  • Plants, Medicinal / chemistry*
  • Stereoisomerism

Substances

  • Alkaloids
  • Indicators and Reagents
  • Indoles
  • psycholeine
  • quadrigemine A