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Expedient on-resin synthesis of peptidic benzimidazoles.

ABSTRACT: The benzimidazole moiety is a ubiquitous pharmacophore present in numerous anthelmintic, antibacterial, antiviral, antineoplastic, and antifungal drugs. While the polypharmacology of this heterocycle has spurred the development of numerous solution-phase syntheses, only a handful of disparate and inefficient methods detailing its synthesis on-resin have been reported. Here we report the concise and expedient syntheses of internal and C-terminal peptidic benzimidazoles - an emerging class of peptide deformylase (PDF)-inhibiting antimicrobials. This method benefits from being performed wholly on solid-phase at room temperature resulting in minimal purification and tolerance of temperature-sensitive functionality.

SUBMITTER: Bird MJ

PROVIDER: S-EPMC6481168 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Expedient on-resin synthesis of peptidic benzimidazoles.

Bird Michael J MJ Silvestri Anthony P AP Dawson Philip E PE

Bioorganic & medicinal chemistry letters 20180503 16

The benzimidazole moiety is a ubiquitous pharmacophore present in numerous anthelmintic, antibacterial, antiviral, antineoplastic, and antifungal drugs. While the polypharmacology of this heterocycle has spurred the development of numerous solution-phase syntheses, only a handful of disparate and inefficient methods detailing its synthesis on-resin have been reported. Here we report the concise and expedient syntheses of internal and C-terminal peptidic benzimidazoles - an emerging class of pept ...[more]

PMID: 29739642

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