Issue 39, 2021

Biphasic electrochemical peptide synthesis


The large amount of waste derived from coupling reagents is a serious drawback of peptide synthesis from a green chemistry viewpoint. To overcome this issue, we report an electrochemical peptide synthesis in a biphasic system. Anodic oxidation of triphenylphosphine (Ph3P) generates a phosphine radical cation, which serves as the coupling reagent to activate carboxylic acids, and produces triphenylphosphine oxide (Ph3P[double bond, length as m-dash]O) as a stoichiometric byproduct. In combination with a soluble tag-assisted liquid-phase peptide synthesis, the selective recovery of desired peptides and Ph3P[double bond, length as m-dash]O was achieved. Given that methods to reduce Ph3P[double bond, length as m-dash]O to Ph3P have been reported, Ph3P[double bond, length as m-dash]O could be a recyclable byproduct unlike byproducts from typical coupling reagents. Moreover, a commercial peptide active pharmaceutical ingredient (API), leuprorelin, was successfully synthesized without the use of traditional coupling reagents.

Graphical abstract: Biphasic electrochemical peptide synthesis

Supplementary files

Article information

Article type
Edge Article
04 Jun 2021
01 Sep 2021
First published
02 Sep 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 12911-12917

Biphasic electrochemical peptide synthesis

S. Nagahara, Y. Okada, Y. Kitano and K. Chiba, Chem. Sci., 2021, 12, 12911 DOI: 10.1039/D1SC03023J

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