Syntheses of 4′-Deoxykanamycin and 4′-Deoxykanamycin B

Abstract

Abstract 4′-Deoxykanamycin (9) was prepared from kanamycin via N-benzyloxycarbonylation, 4″,6″-O-cyclohexylidenation, selective benzoylation at 2′,3′, and 2″-hydroxyl groups, 4′-O-mesylation, 4′-iodination, 4′-hydrogenation, and removal of the protective groups. 4′-Deoxykanamycin B (19) was analogously prepared from kanamycin B. 4′-O-Tosyl derivative of kanamycin B was also led to 19. Selective formylation of the 3′-hydroxyl group of a protected kanamycin B derivative with N,N-dimethylformamide-tosyl chloride followed by mesylation of the unstable 3′-O-formyl derivative also led to 4′-deoxykanamycin B. Throughout the syntheses, the 4′-hydroxyl group of the protected kanamycins was found to be least reactive for benzoylation among the 2′,3′,4′, and 2″-hydroxyl groups. The 13C NMR spectrum of 9 was also measured. It was concluded that 4′-deoxygenation of antibiotics structurally related to kanamycin caused the resonances of 13C-6′ downfield shift.