Hydrophobic acetal and ketal derivatives of mannopeptimycin-alpha and desmethylhexahydromannopeptimycin-alpha: semisynthetic glycopeptides with potent activity against Gram-positive bacteria.
The effect of introducing hydrophobic groups onto the disaccharide portion of the mannopeptimycins has been examined. Under acid-catalyzed conditions dimethyl acetals and ketals react on the terminal mannose of the disaccharide moiety of mannopeptimycin-alpha and the cyclohexylalanyl analogue 2. The preferentially formed monofunctionalized 4,6-acetals and -ketals display potent antibacterial activities against Gram-positive microorganisms, including MRSA, PRSP, and VRE pathogens.
Dushin
Russell G
RG
Wyeth Research, Chemical and Screening Sciences, Medicinal Chemistry, Pearl River, NY 10965, USA. dushinr@wyeth.com
Wang
Ting-Zhong
TZ
Sum
Phaik-Eng
PE
He
Haiyin
H
Sutherland
Alan G
AG
Ashcroft
Joseph S
JS
Graziani
Edmund I
EI
Koehn
Frank E
FE
Bradford
Patricia A
PA
Petersen
Peter J
PJ
Wheless
Karen L
KL
How
David
D
Torres
Nancy
N
Lenoy
Eileen B
EB
Weiss
William J
WJ
Lang
Stanley A
SA
Projan
Steven J
SJ
Shlaes
David M
DM
Mansour
Tarek S
TS
D000080:Acetals / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006020:Glycopeptides; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000080:Acetals; D000900:Anti-Bacterial Agents; D006020:Glycopeptides