Carboxylate-Directed Pd-Catalyzed β-C(sp3)-H Arylation of N-Methyl Alanine Derivatives for Diversification of Bioactive Peptides

Org Lett. 2023 Dec 22;25(50):9008-9013. doi: 10.1021/acs.orglett.3c03616. Epub 2023 Dec 12.

Abstract

This study presents a Pd(II)-catalyzed method for the β-C(sp3)-H arylation of N-Cbz- or N-Fmoc-protected N-methyl alanines, providing ready access to building blocks for N-methylated peptide synthesis. For this transformation, the native carboxylate was exploited as the directing group, attributing its success to the use of a monoprotected amino-pyridine ligand. Its synthetic utility was demonstrated by facile generation of nine analogues of the naturally occurring N-methylated cyclic peptide cycloaspeptide A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine*
  • Carboxylic Acids
  • Catalysis
  • Palladium*
  • Peptides

Substances

  • Palladium
  • Alanine
  • Carboxylic Acids
  • Peptides