Incorporation of Acid-Labile Masking Groups for the Traceless Synthesis of C-Terminal Peptide α-Ketoacids

Org Lett. 2016 Aug 5;18(15):3670-3. doi: 10.1021/acs.orglett.6b01692. Epub 2016 Jul 20.

Abstract

An optimized protocol for the masking of α-ketoacids with acid-labile cyclic acetal protecting groups is reported. Unlike prior approaches, these new conditions allow the synthesis of protected α-ketoacids bearing aromatic, hindered alkyl, and protected polar side chains. Attachment to a Wang-type linker and solid support provides a resin that delivers fully unprotected C-terminal peptide α-ketoacids upon resin cleavage. These peptides are the key starting materials for chemical protein synthesis using the α-ketoacid-hydroxylamine ligation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hydroxylamines / chemistry*
  • Keto Acids / chemical synthesis*
  • Keto Acids / chemistry
  • Molecular Structure
  • Peptides / chemical synthesis*
  • Peptides / chemistry

Substances

  • Hydroxylamines
  • Keto Acids
  • Peptides
  • alpha-ketoacid-hydroxylamine