Ring Expansion of Thiolactams via Imide Intermediates: An Amino Acid Insertion Strategy

Chemistry. 2021 Jan 21;27(5):1620-1625. doi: 10.1002/chem.202005035. Epub 2020 Dec 22.

Abstract

The AgI -promoted reaction of thiolactams with N-Boc amino acids yields an N-(α-aminoacyl) lactam that can rearrange through an acyl transfer process. Boc-deprotection results in convergence to the ring-expanded adduct, thereby facilitating an overall insertion of an amino acid into the thioamide bond to generate medium-sized heterocycles. Application to the site-specific insertion of amino acids into cyclic peptides is demonstrated.

Keywords: acyl transfer; imides; ring expansion; ring insertion; thioamides.

MeSH terms

  • Amino Acids / chemistry*
  • Imides / chemistry*
  • Lactams / chemistry*
  • Peptides, Cyclic / chemistry
  • Thioamides / chemistry*

Substances

  • Amino Acids
  • Imides
  • Lactams
  • Peptides, Cyclic
  • Thioamides