Antineoplastic agents. 550. Synthesis of 10b(s)-epipancratistatin from (+)-narciclasine

J Nat Prod. 2007 Mar;70(3):417-22. doi: 10.1021/np068046e. Epub 2007 Mar 9.

Abstract

By means of a five-step reaction sequence, narciclasine (2a), isolated from Narcissus sp., was converted to 10b(S)-epipancratistatin (3a) in 5.7% overall yield. The key step entailed a radical-initiated 10b,1 C-O cleavage employing tributyltin hydride to yield a B/C cis ring juncture (3b). Biological evaluation of 10b(S)-epipancratistatin (3a) provided evidence that antineoplastic activity was reduced by a factor of 10 when the B/C trans juncture was replaced with a B/C cis ring juncture.

Publication types

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

MeSH terms

  • Amaryllidaceae Alkaloids / chemistry*
  • Amaryllidaceae Alkaloids / isolation & purification
  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Narcissus / chemistry
  • Phenanthridines / chemistry*
  • Phenanthridines / isolation & purification
  • Plants, Medicinal / chemistry
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 10b(s)-epipancratistatin
  • Amaryllidaceae Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Phenanthridines
  • narciclasine