Synthesis and evaluation of selected key methyl ether derivatives of vancomycin aglycon.
A select series of methyl ether derivatives of vancomcyin aglycon were prepared and examined for antimicrobial activity against vancomycin-sensitive Staphylococcus aureus and vancomycin-resistant Enterococci faecalis as well as their binding affinity for D-Ala-D-Ala and D-Ala-D-Lac. The intent of the study was to elucidate the role selected key methyl groups may play in the improvement of the in vitro antimicrobial profile of the tetra methyl ether derivative of vancomycin aglycon against vancomycin-resistant Enterococci faecalis previously reported. In these studies, methodology for selective derivatization of the A-, B-, and D-ring was developed that defines the relative reactivity of the four phenols of vancomycin aglycon, providing a foundation for future efforts for site-directed modification of the vancomycin aglycon core.
Crane
Christine M
CM
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Pierce
Joshua G
JG
Leung
Siegfried S F
SS
Tirado-Rives
Julian
J
Jorgensen
William L
WL
Boger
Dale L
DL
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D013293:Enterococcus faecalis / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008738:Methyl Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D010457:Peptidoglycan / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014640:Vancomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008738:Methyl Ethers; D010457:Peptidoglycan; D014640:Vancomycin