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Synthetic fermentation of ?-peptide macrocycles by thiadiazole-forming ring-closing reactions.

ABSTRACT: Macrocyclic ?-peptides were efficiently prepared using a thiadiazole-forming cyclization reaction between an ?-ketoacid and a thiohydrazide. The linear ?-peptide precursors were assembled from isoxazolidine monomers by ?-ketoacid-hydroxylamine (KAHA) ligations with a bifunctional initiator - a process we have termed 'synthetic fermentation' due to the analogy of producing natural product-like molecules from simpler building blocks. The linear synthetic fermentation products underwent Boc-deprotection/thiadiazole-forming macrocyclization under aqueous, acidic conditions to provide the cyclic products in a one-pot process. This reaction sequence proceeds from easily accessed initiator and monomer building blocks without the need for additional catalysts or reagents, enabling facile production of macrocyclic ?-peptides, a relatively underexplored structural class.

SUBMITTER: Hubert JG

PROVIDER: S-EPMC5896468 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Synthetic fermentation of β-peptide macrocycles by thiadiazole-forming ring-closing reactions.

Hubert Jonathan G JG Stepek Iain A IA Noda Hidetoshi H Bode Jeffrey W JW

Chemical science 20180108 8

Macrocyclic β-peptides were efficiently prepared using a thiadiazole-forming cyclization reaction between an α-ketoacid and a thiohydrazide. The linear β-peptide precursors were assembled from isoxazolidine monomers by α-ketoacid-hydroxylamine (KAHA) ligations with a bifunctional initiator - a process we have termed 'synthetic fermentation' due to the analogy of producing natural product-like molecules from simpler building blocks. The linear synthetic fermentation products underwent Boc-deprote ...[more]

PMID: 29719689

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