Issue 39, 2020

Total synthesis of biseokeaniamides A–C and late-stage electrochemically-enabled peptide analogue synthesis

Abstract

The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A–C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation–nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for building block syntheses. Electrochemically-generated N,O-acetal intermediates are engaged with electron-rich aromatics and organometallic reagents to forge modified amino acids and peptides. The value of this late-stage modification method is highlighted by the expedient and divergent production of bioactive peptide analogues, including compounds which exhibit enhanced cytotoxicity relative to the biseokeaniamide natural products.

Graphical abstract: Total synthesis of biseokeaniamides A–C and late-stage electrochemically-enabled peptide analogue synthesis

Supplementary files

Article information

Article type
Edge Article
Submitted
06 7 2020
Accepted
29 7 2020
First published
30 7 2020
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., 2020,11, 10752-10758

Total synthesis of biseokeaniamides A–C and late-stage electrochemically-enabled peptide analogue synthesis

Y. Lin and L. R. Malins, Chem. Sci., 2020, 11, 10752 DOI: 10.1039/D0SC03701J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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