Synthesis of the Core Tricyclic Ring Domain of (-)-Schulzeine B

J Org Chem. 2015 Aug 7;80(15):7790-6. doi: 10.1021/acs.joc.5b01173. Epub 2015 Jul 28.

Abstract

A formal synthesis of (-)-schulzeine B, a marine natural alkaloid possessing potent antidiabetic activity, has been achieved. A benzo[a]quinolizidin-4-one is a common skeleton of schulzeines (A-C). (-)-Schulzeine B possesses an (S)-stereogenic center at the C-3 carbon. The chiral (3S,11bS)-3-amino-9,11-dimethoxybenzo[a]quinolizidin-4-one has been prepared efficiently from (2-bromo-3,5-dihydroxyphenyl)acetonitrile in 17 steps including (i) a dehydrative intramolecular amination catalyzed by HClO4 and (ii) a proline or boric acid catalyzed transcycloamidation reaction for the construction of the δ-lactam ring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetonitriles / chemistry*
  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Amination
  • Catalysis
  • Cyclization
  • Heterocyclic Compounds, 3-Ring / chemical synthesis*
  • Heterocyclic Compounds, 3-Ring / chemistry
  • Lactams / chemical synthesis*
  • Lactams / chemistry
  • Molecular Structure
  • Quinolizidines / chemistry*
  • Stereoisomerism

Substances

  • (2-bromo-3,5-dihydroxyphenyl)acetonitrile
  • 3-amino-9,11-dimethoxybenzo(a)quinolizidin-4-one
  • Acetonitriles
  • Alkaloids
  • Heterocyclic Compounds, 3-Ring
  • Lactams
  • Quinolizidines
  • schulzeine B