TY - JOUR
T1 - Model for antibiotic optimization via neoglycosylation
T2 - Synthesis of liponeoglycopeptides active against VRE
AU - Griffith, Byron R.
AU - Krepel, Candace
AU - Fu, Xun
AU - Blanchard, Sophie
AU - Ahmed, Aqeel
AU - Edmiston, Charles E.
AU - Thorson, Jon S.
PY - 2007/7/4
Y1 - 2007/7/4
N2 - The neoglycosylation of a methoxyamine-appended vancomycin aglycon with all possible N′-decanoylglucopyranose and N′-biphenoylglucopyranose regioisomers led to the production of a focused set of liponeoglycopeptide variants in good yields and with excellent stereoselectivity. High-throughput antibacterial assays employing a unique set of vancomycin-resistant Enterococci faecalis and Enterococci faecium clinical isolates revealed that the nature and regiochemistry of glycosyl lipidation modulated vancomycin-resistent Enterococci potency. In contrast to prior work with lipoglycopeptides, this study reveals the glucose C3′ or C4′ as the optimal position for neoglycopeptide lipidation. This purely chemical method for the diversification of the glycolipid portion of lipoglycopeptide antibiotics is simple to perform on a large scale, requires minimal synthetic effort in sugar donor preparation, and provides access to highly active antibiotics that are not easily prepared by other state-of-the-art methods.
AB - The neoglycosylation of a methoxyamine-appended vancomycin aglycon with all possible N′-decanoylglucopyranose and N′-biphenoylglucopyranose regioisomers led to the production of a focused set of liponeoglycopeptide variants in good yields and with excellent stereoselectivity. High-throughput antibacterial assays employing a unique set of vancomycin-resistant Enterococci faecalis and Enterococci faecium clinical isolates revealed that the nature and regiochemistry of glycosyl lipidation modulated vancomycin-resistent Enterococci potency. In contrast to prior work with lipoglycopeptides, this study reveals the glucose C3′ or C4′ as the optimal position for neoglycopeptide lipidation. This purely chemical method for the diversification of the glycolipid portion of lipoglycopeptide antibiotics is simple to perform on a large scale, requires minimal synthetic effort in sugar donor preparation, and provides access to highly active antibiotics that are not easily prepared by other state-of-the-art methods.
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U2 - 10.1021/ja068602r
DO - 10.1021/ja068602r
M3 - Article
C2 - 17564440
AN - SCOPUS:34447255199
SN - 0002-7863
VL - 129
SP - 8150
EP - 8155
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 26
ER -