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A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin 'in-chloride'.

ABSTRACT: In an effort to rapidly access vancomycin analogues bearing diverse functionality at the 6c-Cl (the 'in-chloride') position, a two-step dechlorination/cross-coupling protocol was developed. Conditions for efficient cross-coupling of the relatively unreactive 6c-Cl group were found that ensure high conversion with minimal product decomposition. A set of 2c-dechloro-6c-functionalized vancomycin derivatives was prepared, and antibiotic activities of the compounds were evaluated against a panel of vancomycin-resistant and vancomycin-susceptible strains. Results from biological testing further underscore the steric sensitivity of vancomycin's binding pocket.

SUBMITTER: Wadzinski TJ

PROVIDER: S-EPMC4728044 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin 'in-chloride'.

Wadzinski Tyler J TJ Gea Katherine D KD Miller Scott J SJ

Bioorganic & medicinal chemistry letters 20151211 3

In an effort to rapidly access vancomycin analogues bearing diverse functionality at the 6c-Cl (the 'in-chloride') position, a two-step dechlorination/cross-coupling protocol was developed. Conditions for efficient cross-coupling of the relatively unreactive 6c-Cl group were found that ensure high conversion with minimal product decomposition. A set of 2c-dechloro-6c-functionalized vancomycin derivatives was prepared, and antibiotic activities of the compounds were evaluated against a panel of v ...[more]

PMID: 26725950

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