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Synthesis of L-cyclic tetrapeptides by backbone amide activation CyClick strategy.

ABSTRACT: Cyclic tetrapeptides exhibit high cellular permeability and a wide range of biological properties and thus have gained great interest in the field of medicinal chemistry. We synthesized highly strained 12-membered head to tail cyclic peptides with varying reactive amino acids, without oligomerization using the exclusively intramolecular CyClick chemistry. This occurs by a two-step process involving the low-energy formation of a 15 atom-containing cyclic imine, followed by a chemoselective ring contraction of the peptide backbone generating a highly strained 12 atom-containing cyclic tetrapeptide. This reaction exhibited high substrate scope and generated head to tail cyclic tetrapeptides with varying amino acids at the N-terminus, showing chemoselectivity without the need for side group protection.

SUBMITTER: Wills R

PROVIDER: S-EPMC10664817 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Synthesis of L-cyclic tetrapeptides by backbone amide activation CyClick strategy.

Wills Rachel R Adebomi Victor V Spancake Caroline C Cohen Ryan D RD Raj Monika M

Tetrahedron 20221005

Cyclic tetrapeptides exhibit high cellular permeability and a wide range of biological properties and thus have gained great interest in the field of medicinal chemistry. We synthesized highly strained 12-membered head to tail cyclic peptides with varying reactive amino acids, without oligomerization using the exclusively intramolecular CyClick chemistry. This occurs by a two-step process involving the low-energy formation of a 15 atom-containing cyclic imine, followed by a chemoselective ring c ...[more]

PMID: 37994371

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