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. 2021 Sep 2;12(39):12911-12917.
doi: 10.1039/d1sc03023j. eCollection 2021 Oct 13.

Biphasic electrochemical peptide synthesis

Shingo Nagahara  1 , Yohei Okada  1 , Yoshikazu Kitano  1 , Kazuhiro Chiba  1
Affiliations

Biphasic electrochemical peptide synthesis

Shingo Nagahara et al. Chem Sci. .

Abstract

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.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. (a) Conventional and (b) greener peptide bond formation. (c) Electrochemical peptide bond formation.
Fig. 1
Fig. 1. Electrochemical peptide synthesis utilizing soluble tag-assisted method.
Scheme 2
Scheme 2. (A) Biphasic electrochemical synthesis of leuprorelin, and (B) HPLC analysis of leuprorelin (protected form, R. T. = 28.14) (5).
See this image and copyright information in PMC

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