A Modular Formal Total Synthesis of (±)-Cycloclavine

J Org Chem. 2016 Feb 19;81(4):1723-30. doi: 10.1021/acs.joc.5b02815. Epub 2016 Feb 4.

Abstract

Cycloclavine is a clavine-type Ergot alkaloid noteworthy for its unique pentacyclic skeleton featuring a 3-azabicyclo[3.1.0]hexane substructure. A short convergent route to the racemic alkaloid is described which comprises only eight linear steps and requires only four chromatographic purifications. The two key building blocks can be prepared in high yield from commercially available starting materials. Two consecutive coupling reactions, namely a selective alkylation of a dienolate and a Heck reaction, are the key steps of the reaction sequence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cyclization
  • Hexanes / chemistry*
  • Indole Alkaloids / chemical synthesis*
  • Indole Alkaloids / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • 3-azabicyclo(3.1.0)hexane
  • Bridged Bicyclo Compounds, Heterocyclic
  • Hexanes
  • Indole Alkaloids
  • cycloclavine
  • n-hexane