Jump to main content
Jump to site search

Issue 40, 2020
Previous Article Next Article

An optimized protocol for the synthesis of N-2-hydroxybenzyl-cysteine peptide crypto-thioesters

Author affiliations

Abstract

We herein report a robust upgraded synthetic protocol for the synthesis of N-Hnb-Cys crypto-thioester peptides, useful building blocks for segment-based chemical protein synthesis through native chemical ligation. We recently observed the formation of an isomeric co-product when using a different solid support than the originally-reported one, thus hampering the general applicability of the methodology. We undertook a systematic study to characterize this compound and identify the parameters favouring its formation. We show here that epimerization from L- to D-cysteine occurred during the key solid-supported reductive amination step. We also observed the formation of imidazolidinones by-products arising from incomplete reduction of the imine. Structural characterization combined with the deciphering of underlying reaction mechanisms allowed us to optimize conditions that abolished the formation of all these side-products.

Graphical abstract: An optimized protocol for the synthesis of N-2-hydroxybenzyl-cysteine peptide crypto-thioesters

Back to tab navigation

Supplementary files

Article information


Submitted
22 Aug 2020
Accepted
18 Sep 2020
First published
09 Oct 2020

Org. Biomol. Chem., 2020,18, 8199-8208
Article type
Paper

An optimized protocol for the synthesis of N-2-hydroxybenzyl-cysteine peptide crypto-thioesters

S. A. Abboud and V. Aucagne, Org. Biomol. Chem., 2020, 18, 8199
DOI: 10.1039/D0OB01737J

Social activity

Search articles by author

Spotlight

Advertisements