title: Catalytic site-selective thiocarbonylations and deoxygenations of vancomycin reveal hydroxyl-dependent conformational effects.
abstract: We have examined peptide-based catalysts for the site-selective thiocarbonylation of a protected form of vancomycin. Several catalysts were identified that either enhanced or altered the inherent selectivity profile exhibited by the substrate. Two catalysts, one identified through screening and another through rational design, were demonstrated to be effective on 0.50-g scale. Deoxygenations led ultimately to two new deoxy-vancomycin derivatives, and surprising conformational consequences of deoxygenation were revealed for one of the new compounds. These effects were mirrored in the biological activities of the new analogues and support a structural role for certain hydroxyls in the native structure.
authors.affiliation: Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107, USA.
authors.forename: Brandon S
authors.initials: BS
authors.lastname: Fowler
authors.forename: Kai M
authors.initials: KM
authors.lastname: Laemmerhold
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Miller
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D056569:Enterococcaceae / Q000187:drug effects; D006801:Humans; D007536:Isomerism; D008958:Models, Molecular; D008968:Molecular Conformation; D010100:Oxygen / Q000737:chemistry; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000737:chemistry; D014640:Vancomycin / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D013438:Sulfhydryl Compounds; D014640:Vancomycin; D010100:Oxygen