STUDY ON FLUORINATION OF 2,3-DIDEOXY-2,3-(N-TOSYLEPIMINO)-ALPHA-D-ALLOPYRANOSIDES, AND SYNTHESIS OF 3'-DEOXY-3'-FLUOROKANAMYCIN-B AND 3',4'-DIDEOXY-3'-FLUOROKANAMYCIN-B

Reaction of the structurally rigid methyl 2,3-dideoxy-4.6-O-isopropylidene-2,3-(N-tosylepimino)-alpha-D-allopyranoside (6) with KHF2 in DMF at 150-degrees gave initially methyl 2.3-dideoxy-2-fluoro-4.6-O-isopro-pylidene-3-tosylamido-alpha-D-altropyranoside (10) by N-tosylepimine-ring opening. and 10 was gradually converted into the stable methyl 2,3-dideoxy-3-fluoro-4.6-O-isopropylidene-2-tosylamido-alpha-D-glucopyranoside (11). A reversible mechanism involving 6 and 10 has been proposed. In the mobile methyl 2,3-dideoxy-2,3-(N-tosylepimino)-alpha-D-allopyranoside (7) and the corresponding 4,6-di-O-acetyl (8) and -di-O-methyl derivatives (9). reactions with KHF2 proceeded comparatively rapidly giving the corresponding 3-deoxy-3-fluoro-alpha-D-glucopyranosides as the major products. A slightly different reaction mechanism for the mobile compounds has been proposed. By application of this study. 3'-deoxy-3'-fluorokanamycin B was prepared by treatment of 4'',6''-O-cyclohexylidene-2'-deamino-3'-deoxy-3'-epi-6'-N-methoxycarbonyl-1,3,3''-tri-N-tosyl-2',3'-(N-tosylepimino)kanamycin B (21) with KHF2 as the key reaction. 3',4'-Dideoxy-3'-fluorokanamycin B was also prepared. Both compounds were active against resistant bacteria producing 3'-modifying enzymes.