title: 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.
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, United States.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Wadzinski
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, United States.
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Gea
authors.affiliation: Department of Chemistry, Yale University, PO Box 208107, New Haven, CT 06520-8107, United States. Electronic address: scott.miller@yale.edu.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D002712:Chlorides / Q000737:chemistry*; D054879:Halogenation; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D020713:Vancomycin Resistance / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001897:Boronic Acids; D002712:Chlorides; D014640:Vancomycin
keywords: Cross-coupling; Vancomycin; Vancomycin analogues