Chemical modification of kanamycin A. II. Nucleophilic displacement reactions of kanamycin A 4"-sulfonates

Reactions of 2 ',3 ',4',2",6"-penta-O-acetyl-tetra-N-tert-butyloxycarbonyl-kanamycin-A-4"-brosylate (4b) or -4“-triflate (4c) with acetate, thiolacetate, azide, and fluoride, respectively, result in the formation of the corresponding derivatives of 4"epi-kanamycin A (5a-d)) While 4b invariably forms an elimination by-product (9), the only side—reaction of 4c consists in a neighboring group attack with formation of a 3“,epi-4”-cyclic urethane (7). Removal of the protecting groups yields 4 “-epi- (6a), 4”-thio-4 “-epi-(6b), 4”-deoxy-4w-fluoro-4h-epi-(6d), 4“-azido-4”-deoxy-4 epi- (6c), and after hydrogenation of the latter, 4"-ammo-rr-deoxy-4 ”~epi-kanamycin A (6 f). Methyl 2,6-di-0-acetyl-3-amino-3-N-tert-butyloxy-carbony1-3-deoxy-4-O-triflyl-g-g-glucopyranoside (lb) served as a model to anticipate preparation, handling, and reactivity of 4c.