Issue 4, 2015

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).

Graphical abstract: Synthesis of isoxazolidine-containing uridine derivatives as caprazamycin analogues

Supplementary files

Article information

Article type
Paper
Submitted
08 Oct 2014
Accepted
14 Nov 2014
First published
14 Nov 2014

Org. Biomol. Chem., 2015,13, 1187-1197

Author version available

Synthesis of isoxazolidine-containing uridine derivatives as caprazamycin analogues

M. Yamaguchi, A. Matsuda and S. Ichikawa, Org. Biomol. Chem., 2015, 13, 1187 DOI: 10.1039/C4OB02142H

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