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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:26

Article

Wadzinski, Tyler J.¹  Gea, Katherine D.¹  Miller, Scott J.¹ 

[1] Yale Univ, Dept Chem, POB 208107, New Haven, CT 06520 USA

关键词: Vancomycin;    Vancomycin analogues;    Cross-coupling;   

DOI  :  10.1016/j.bmcl.2015.12.027

来源: Elsevier

【 摘 要 】

In an effort to rapidly access vancomycin analogues bearing diverse functionality at the 6(c)-Cl (the 'in-chloride') position, a two-step dechlorination/cross-coupling protocol was developed. Conditions for efficient cross-coupling of the relatively unreactive 6(c)-Cl group were found that ensure high conversion with minimal product decomposition. A set of 2(c)-dechloro-6(c)-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. (C) 2015 Elsevier Ltd. All rights reserved.

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