Rhodium-Catalyzed Regioselective C3Ar Functionalization of Tyrosines with Maleimides and Its Late-Stage Peptide Exemplification

Org Lett. 2023 Oct 27;25(42):7673-7677. doi: 10.1021/acs.orglett.3c02994. Epub 2023 Oct 18.

Abstract

Pyridyloxy-directed Rh(III)-catalyzed regioselective C3Ar-H alkenylation of protected tyrosines was achieved with N-aryl and N-alkyl maleimides, furnishing a series of maleimide-appended tyrosine-based unnatural amino acids in good yields. Further, the late-stage exemplification of the strategy was successfully accomplished on tyrosine-containing dipeptides, tripeptides, and tetrapeptides in moderate reactivity. Also, the chemical applications of the strategy were successfully executed toward nailing tyrosine with other amino acids via a maleimide linker and intramolecular hydroarylation to produce tyrosine-centered stapled products and succinimide-glued macrocyclized products, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids
  • Catalysis
  • Maleimides / chemistry
  • Molecular Structure
  • Peptides
  • Rhodium* / chemistry
  • Tyrosine

Substances

  • Rhodium
  • maleimide
  • Tyrosine
  • Amino Acids
  • Maleimides
  • Peptides