Asymmetric total synthesis of the 1-epi-aglycon of the cripowellins A and B

J Org Chem. 2005 Dec 9;70(25):10538-51. doi: 10.1021/jo0518093.

Abstract

[structure: see text] The unusual [5.3.2]-bicyclic structure of the insecticidal Amaryllidaceae alkaloids cripowellin A (1) and B (2) has been synthesized for the first time via a sequence of Sharpless dihydroxylation, ring-closing metathesis, and intramolecular Heck reaction. The asymmetric synthesis of the 1-epi-aglycon 82 proceeds with virtually complete diastereo- and enantioselectivity (de, ee > or = 98%) in 13 steps and an overall yield of 5.6%. In addition, three alternative approaches toward the aglycon 3 are also described focusing on (1) the alkylation of the 2-benzazepinedithianes 35 and 36 with the electrophile 11, (2) a radical cyclization of the precursor (R/S,S,S)-39, and (3) an intramolecular arylation reaction of the aryl ketone 47.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkylation
  • Amaryllidaceae Alkaloids / chemical synthesis*
  • Cyclization
  • Stereoisomerism

Substances

  • Alkaloids
  • Amaryllidaceae Alkaloids
  • cripowellin A
  • cripowellin B