Synthesis of all low-energy stereoisomers of the tris(pyrrolidinoindoline) alkaloid hodgkinsine and preliminary assessment of their antinociceptive activity

J Org Chem. 2007 Oct 12;72(21):7909-14. doi: 10.1021/jo7013643. Epub 2007 Sep 21.

Abstract

The previously unknown stereoisomers 3, 4, ent-1, and ent-4 of the tris(pyrrolidinoindoline) alkaloids hodgkinsine (1) and hodgkinsine B (2) were prepared by stereocontrolled total synthesis. In each synthesis, a catalyst-controlled intramolecular Heck reaction was the key step in appending a third cis-pyrrolidinoindoline ring to a hexacyclic chimonanthine precursor. Results of the preliminary evaluation of these hodgkinsine stereoisomers in the tail flick and capsaicin pain models are reported.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Alkaloids / therapeutic use
  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / chemistry
  • Analgesics, Non-Narcotic / pharmacology
  • Analgesics, Non-Narcotic / therapeutic use
  • Animals
  • Disease Models, Animal
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Mice
  • Molecular Structure
  • Pain / drug therapy
  • Stereoisomerism
  • Thermodynamics

Substances

  • Alkaloids
  • Analgesics, Non-Narcotic
  • Indoles
  • hodgkinsine