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Synthesis of bioactive and stabilized cyclic peptides by macrocyclization using C(sp³)-H activation.

ABSTRACT: Cyclic peptides have attracted increasing attention in recent years due to their ability to inhibit protein-protein interactions. Current strategies to prepare cyclic peptides often rely on functional amino acid side chains or the incorporation of unnatural amino acids, thus limiting their structural diversity. Here, we describe the development of a highly versatile peptide macrocyclization strategy through a palladium-catalyzed C(sp³)-H activation and the synthesis of cyclic peptides featuring unique hydrocarbon linkages between the β-carbon of amino acids and the aromatic side chains of Phe and Trp. We demonstrate that such peptides exhibit improved biological properties compared to their acyclic counterparts. Finally, we applied this method in the synthesis of the natural product celogentin C.

SUBMITTER: Tang J

PROVIDER: S-EPMC5590095 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Synthesis of bioactive and stabilized cyclic peptides by macrocyclization using C(sp3)-H activation.

Tang Jian J He Yadong Y Chen Hongfei H Sheng Wangjian W Wang Huan H

Chemical science 20170419 6

Cyclic peptides have attracted increasing attention in recent years due to their ability to inhibit protein-protein interactions. Current strategies to prepare cyclic peptides often rely on functional amino acid side chains or the incorporation of unnatural amino acids, thus limiting their structural diversity. Here, we describe the development of a highly versatile peptide macrocyclization strategy through a palladium-catalyzed C(sp3)-H activation and the synthesis of cyclic peptides ...[more]

PMID: 28936334

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