Ring Expansion of Thiolactams via Imide Intermediates: An Amino Acid Insertion Strategy

Jing Shang; Varsha J Thombare; Carlie L Charron; Uta Wille; Craig A Hutton

Journal article

Ring Expansion of Thiolactams via Imide Intermediates: An Amino Acid Insertion Strategy

Jing Shang, Varsha J Thombare, Carlie L Charron, Uta Wille, Craig A Hutton

Chemistry - A European Journal | WILEY-V C H VERLAG GMBH | Published : 2020

DOI: 10.1002/chem.202005035

Abstract

The AgI -promoted reaction of thiolactams with N-Boc amino acids yields an N-(α-aminoacyl) lactam that can rearrange through an acyl transfer process. Boc-deprotection results in convergence to the ring-expanded adduct, thereby facilitating an overall insertion of an amino acid into the thioamide bond to generate medium-sized heterocycles. Application to the site-specific insertion of amino acids into cyclic peptides is demonstrated.

University of Melbourne Researchers

Uta Wille Author Chemistry

Varsha Thombare Author Biochemistry and Pharmacology

Craig Hutton Author Chemistry

Related Projects (2)

New synthetic strategies to small cyclic peptides

This project aims to invent new synthetic strategies that enable chemical manipulation of small cyclic peptides, a promising class of biolog..

A new direction in peptide synthesis: an N-to-C approach using thioamides

The synthesis of amide bonds is one of the most important techniques in organic chemistry. Amide bonds are formed in the production of 65% o..

Grants

Awarded by Australian Research Council

Funding Acknowledgements

This work was supported by the Australian Research Council (DP180101804 and DP150100692) and the High Performance Computing Facilities of The University of Melbourne. We acknowledge the support of the Bio21 Molecular Science and Biotechnology Institute MSP and Peptide Technologies facilities. V.T. acknowledges the award of a Norma Hilda Schuster Scholarship.