title: Hydrophobic acetal and ketal derivatives of mannopeptimycin-alpha and desmethylhexahydromannopeptimycin-alpha: semisynthetic glycopeptides with potent activity against Gram-positive bacteria.
abstract: 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.
authors.affiliation: Wyeth Research, Chemical and Screening Sciences, Medicinal Chemistry, Pearl River, NY 10965, USA. dushinr@wyeth.com
authors.forename: Russell G
authors.initials: RG
authors.lastname: Dushin
authors.forename: Ting-Zhong
authors.initials: TZ
authors.lastname: Wang
authors.forename: Phaik-Eng
authors.initials: PE
authors.lastname: Sum
authors.forename: Haiyin
authors.initials: H
authors.lastname: He
authors.forename: Alan G
authors.initials: AG
authors.lastname: Sutherland
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Ashcroft
authors.forename: Edmund I
authors.initials: EI
authors.lastname: Graziani
authors.forename: Frank E
authors.initials: FE
authors.lastname: Koehn
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Bradford
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Petersen
authors.forename: Karen L
authors.initials: KL
authors.lastname: Wheless
authors.forename: David
authors.initials: D
authors.lastname: How
authors.forename: Nancy
authors.initials: N
authors.lastname: Torres
authors.forename: Eileen B
authors.initials: EB
authors.lastname: Lenoy
authors.forename: William J
authors.initials: WJ
authors.lastname: Weiss
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Lang
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Projan
authors.forename: David M
authors.initials: DM
authors.lastname: Shlaes
authors.forename: Tarek S
authors.initials: TS
authors.lastname: Mansour
mesh_terms: 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
chemical_list: D000080:Acetals; D000900:Anti-Bacterial Agents; D006020:Glycopeptides