Discovery of a novel series of semisynthetic vancomycin derivatives effective against vancomycin-resistant bacteria.
Novel semisynthetic vancomycin derivatives with antibacterial activity against vancomycin-resistant S. aureus (VRSA) were prepared. Replacement of Cl groups of vancomycin by Suzuki-Miyaura cross-coupling reaction, which gave the title compounds, is described for the first time. Introduction of a carbon substituent at the amino acid residue 2 of vancomycin led to an enhancement of antibacterial activity against vancomycin-resistant strains, whereas the additional introduction at the amino acid residue 6 resulted in a reduction in activity even against vancomycin-susceptible strains.
Nakama
Yuki
Y
Graduate School of Life Sciences, Tohoku University, Sendai 981-8555, Japan.
Yoshida
Osamu
O
Yoda
Masanori
M
Araki
Keisuke
K
Sawada
Yuri
Y
Nakamura
Jun
J
Xu
Shu
S
Miura
Kenji
K
Maki
Hideki
H
Arimoto
Hirokazu
H
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D055808:Drug Discovery; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D014640:Vancomycin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D014640:Vancomycin