Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 41, 2019
Previous Article Next Article

Ketoxime peptide ligations: oxidative couplings of alkoxyamines to N-aryl peptides

Author affiliations

Abstract

Chemoselective ligation methods that preserve or introduce side chain diversity are critical for chemical synthesis of peptides and proteins. Starting from ketone substrates instead of aldehydes in oxime ligation reactions would allow substitution at the site of ligation; however, synthetic challenges to readily access ketone derivatives from common amino acid building blocks have precluded the widespread use of ketoxime peptide ligation reactions thus far. Moreover, ketones are typically much slower to react in condensation reactions compared to aldehydes. Here, one-pot catalyst-free oxidative couplings of α-substituted N-aryl peptides with alkoxyamines provide access to oxime linkages with diverse side chains. Electron-rich N-(p-Me2N-phenyl)-amino acids possessing substituents at the α-carbon were found to be uniquely capable of undergoing site-selective α-C–H oxidations in situ under an O2 atmosphere at neutral pH. Comparative studies with N-arylglycinyl peptides revealed that substitution at the α-carbon caused notable changes in reactivity, with greater sensitivity to solvent and buffer salt composition.

Graphical abstract: Ketoxime peptide ligations: oxidative couplings of alkoxyamines to N-aryl peptides

Back to tab navigation

Supplementary files

Article information


Submitted
12 Aug 2019
Accepted
22 Aug 2019
First published
29 Aug 2019

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2019,10, 9506-9512
Article type
Edge Article

Ketoxime peptide ligations: oxidative couplings of alkoxyamines to N-aryl peptides

Q. A. E. Guthrie, H. A. Young and C. Proulx, Chem. Sci., 2019, 10, 9506
DOI: 10.1039/C9SC04028E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

Reproduced material should be attributed as follows:

  • For reproduction of material from NJC:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
  • For reproduction of material from PCCP:
    [Original citation] - Published by the PCCP Owner Societies.
  • For reproduction of material from PPS:
    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
  • For reproduction of material from all other RSC journals:
    [Original citation] - Published by The Royal Society of Chemistry.

Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.


Social activity

Search articles by author

Spotlight

Advertisements