Enantioselective synthesis of a GPR40 agonist AMG 837 via catalytic asymmetric conjugate addition of terminal alkyne to α,β-unsaturated thioamide

Org Lett. 2011 Mar 4;13(5):952-5. doi: 10.1021/ol102998w. Epub 2011 Feb 3.

Abstract

A concise enantioselective synthetic route to a potent GPR40 agonist AMG 837 is described. The crucial catalytic asymmetric conjugate addition of terminal alkyne was promoted by a soft Lewis acid/hard Brønsted base cooperative catalyst, allowing efficient construction of the requisite stereogenic center. The thioamide functional group is key to both activation in asymmetric alkynylation and facile transformation into carboxylic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Catalysis
  • Combinatorial Chemistry Techniques
  • Humans
  • Molecular Structure
  • Receptors, G-Protein-Coupled / agonists*
  • Stereoisomerism
  • Thioamides / chemistry*

Substances

  • AMG 837
  • Alkynes
  • Biphenyl Compounds
  • FFAR1 protein, human
  • Receptors, G-Protein-Coupled
  • Thioamides