5-Methylisoxazole-3-carboxamide-Directed Palladium-Catalyzed γ-C(sp(3))-H Acetoxylation and Application to the Synthesis of γ-Mercapto Amino Acids for Native Chemical Ligation

Org Lett. 2016 Jun 3;18(11):2696-9. doi: 10.1021/acs.orglett.6b01160. Epub 2016 May 24.

Abstract

Palladium-catalyzed acetoxylation of the primary γ-C(sp(3))-H bonds in the amino acids Val, Thr, and Ile was achieved using a newly discovered 5-methylisoxazole-3-carboxamide directing group. The γ-acetoxylated α-amino acid derivatives could be easily converted to γ-mercapto amino acids, which are useful for native chemical ligation (NCL). The first application of NCL at isoleucine in the semisynthesis of a Xenopus histone H3 protein was also demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemical synthesis*
  • Catalysis
  • Histones / chemistry
  • Hydrogen Bonding
  • Isoxazoles / chemistry*
  • Molecular Structure
  • Palladium / chemistry*
  • Xenopus Proteins / chemistry

Substances

  • 5-methylisoxazole-3-carboxamide
  • Amino Acids
  • Histones
  • Isoxazoles
  • Xenopus Proteins
  • Palladium