Improved synthesis of (S)-N-Boc-5-oxaproline for protein synthesis with the α-ketoacid-hydroxylamine (KAHA) ligation

Bioorg Med Chem. 2017 Sep 15;25(18):4996-5001. doi: 10.1016/j.bmc.2017.06.019. Epub 2017 Jun 15.

Abstract

We describe a new route for the synthesis of (S)-N-Boc-5-oxaproline. This building block is a key element for the chemical synthesis of proteins with the α-ketoacid-hydroxylamine (KAHA) ligation. The new synthetic pathway to the enantiopure oxaproline is based on a chiral amine mediated enantioselective conjugate addition of a hydroxylamine to trans-4-oxo-2-butenoate. This route is practical, scalable and economical and provides decagram amounts of material for protein synthesis and conversion to other protected forms of (S)-oxaproline.

Keywords: (S)-N-Boc-5-oxaproline; Chemical ligation; Chemical protein synthesis; KAHA ligation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / chemistry
  • Hydroxylamines / chemistry*
  • Magnetic Resonance Spectroscopy
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / chemistry
  • Proteins / chemical synthesis*
  • Proteins / chemistry
  • Stereoisomerism

Substances

  • Aldehydes
  • Hydroxylamines
  • Proteins
  • alpha-ketoacid-hydroxylamine
  • 5-oxaproline
  • Proline