A stepwise dechlorination/cross-coupling strategy to diversify the vancomycin 'in-chloride'. Issue 3 (1st February 2016)

• Record Type: Journal Article
• Authors: Wadzinski, Tyler J.; Gea, Katherine D.; Miller, Scott J.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 3(2016)
• Page Start: 1025
• Page End: 1028
• Publication Date: 2016-02-01
• Subjects: Vancomycin -- Vancomycin analogues -- Cross-coupling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.12.027
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.