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Bioorg Med Chem Lett. 2016 Feb 1;26(3):1025-1028. doi: 10.1016/j.bmcl.2015.12.027. Epub 2015 Dec 11.

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

Author information

1
Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, United States.
2
Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, United States. Electronic address: scott.miller@yale.edu.

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.

KEYWORDS:

Cross-coupling; Vancomycin; Vancomycin analogues

PMID:
26725950
PMCID:
PMC4728044
DOI:
10.1016/j.bmcl.2015.12.027
[Indexed for MEDLINE]
Free PMC Article

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