Issue 8, 2018

Synthetic fermentation of β-peptide macrocycles by thiadiazole-forming ring-closing reactions

Abstract

Macrocyclic β-peptides were efficiently prepared using a thiadiazole-forming cyclization reaction between an α-ketoacid and a thiohydrazide. The linear β-peptide precursors were assembled from isoxazolidine monomers by α-ketoacid-hydroxylamine (KAHA) ligations with a bifunctional initiator – a process we have termed ‘synthetic fermentation’ due to the analogy of producing natural product-like molecules from simpler building blocks. The linear synthetic fermentation products underwent Boc-deprotection/thiadiazole-forming macrocyclization under aqueous, acidic conditions to provide the cyclic products in a one-pot process. This reaction sequence proceeds from easily accessed initiator and monomer building blocks without the need for additional catalysts or reagents, enabling facile production of macrocyclic β-peptides, a relatively underexplored structural class.

Graphical abstract: Synthetic fermentation of β-peptide macrocycles by thiadiazole-forming ring-closing reactions

Supplementary files

Article information

Article type
Edge Article
Submitted
25 Nov. 2017
Accepted
05 Janv. 2018
First published
08 Janv. 2018
This article is Open Access

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

Chem. Sci., 2018,9, 2159-2167

Synthetic fermentation of β-peptide macrocycles by thiadiazole-forming ring-closing reactions

J. G. Hubert, I. A. Stepek, H. Noda and J. W. Bode, Chem. Sci., 2018, 9, 2159 DOI: 10.1039/C7SC05057G

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements