Macrocyclization of Maleimide-Decorated Peptides via Late-Stage Rh(III)-Catalyzed Trp(C7) Alkenylation

Org Lett. 2023 Apr 14;25(14):2456-2460. doi: 10.1021/acs.orglett.3c00601. Epub 2023 Mar 31.

Abstract

Here, we report a novel strategy for constructing maleimide-containing peptides and cyclic peptides using Rh(III)-catalyzed tryptophan (Trp) (C7) alkenylation, which is challenging due to the inherent reactivity of the indole benzenoid ring. This method is scalable and exhibits broad substrate scope. The utility of this protocol could further be demonstrated by the synthesis of peptide conjugates with natural products and amino acids as well as the construction of maleimide-braced cyclic peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Maleimides
  • Peptides* / chemistry
  • Peptides, Cyclic / chemistry
  • Tryptophan* / chemistry

Substances

  • Tryptophan
  • Peptides
  • Peptides, Cyclic
  • maleimide
  • Maleimides