title: Synthesis of isoxazolidine-containing uridine derivatives as caprazamycin analogues.
abstract: Simplification of caprazamycins, which are promising antibacterial nucleoside natural products, was conducted by scaffold-hopping of the structurally complex diazepanone moiety to the isoxazolidine scaffold. The designed isoxazolidine-containing uridine derivatives were synthesized by an intramolecular 1,3-dipolar cycloaddition of alkenyl nitrone as a key step. The lactone-fused isoxazolidine intermediate was easily converted to the target compounds by sequential introduction of key substituents upon ring-opening the lactone moiety by nucleophilic substitution and electrophilic capping of the resulting primary alcohol. Several analogues exhibited good activity against H. influenzae ATCC 10211 (MIC 0.25-0.5 μg mL(-1)) and moderate activity against vancomycin-resistant E. faecalis SR7914 (MIC 4-8 μg mL(-1)).
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. ichikawa@pharm.hokudai.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ichikawa
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D007555:Isoxazoles / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D007555:Isoxazoles; D014529:Uridine