Synlett 2020; 31(03): 199-204
DOI: 10.1055/s-0039-1691495
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© Georg Thieme Verlag Stuttgart · New York

Backbone-Enabled Peptide Macrocyclization through Late-Stage Palladium-Catalyzed C–H Activation

Zengbing Bai
,
Huan Wang
This study was financially supported by the NSF of China (Grants 21778030 and 21922703 to H.W.) and by the Fundamental Research Funds for the Central Universities (Grants 14380138 and 14380138 to H.W.).
Further Information

Publication History

Received: 17 October 2019

Accepted after revision: 06 November 2019

Publication Date:
09 December 2019 (online)


Abstract

Peptide macrocycles are widely used in fields ranging from medicinal chemistry to materials science. Efficient chemical methods for the synthesis of cyclic peptides with novel three-dimensional structures are highly desired to facilitate the development of this unique class of compounds. However, the range of methods available for constructing peptide macrocycles is limited compared with that for small molecules. We recently developed new methods for synthesizing highly constrained cyclic peptides with C–C crosslinks through Pd-catalyzed C–H activation reactions. These methods use endogenous backbone amides as directing groups and, therefore, have the potential for use in late-stage functionalization of peptide natural products.

 
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