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. 2017 Jan 16;56(3):728-732.
doi: 10.1002/anie.201608207. Epub 2016 Nov 17.

Decarboxylative Peptide Macrocyclization through Photoredox Catalysis

Stefan J McCarver  1 , Jennifer X Qiao  2 , Joseph Carpenter  2 , Robert M Borzilleri  2 , Michael A Poss  2 , Martin D Eastgate  2 , Michael M Miller  2 , David W C MacMillan  1
Affiliations

Decarboxylative Peptide Macrocyclization through Photoredox Catalysis

Stefan J McCarver et al. Angew Chem Int Ed Engl. .

Abstract

A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ-amino acids and is tolerant of functionalities present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR-005, a somatostatin analogue that is currently in clinical trials.

Keywords: Michael addition; decarboxylation; macrocycles; peptides; photoredox catalysis.

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Figures

Scheme 1
Scheme 1
Proposed Decarboxylative Peptide Macrocyclization
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