Synthesis of 4′-deoxy-4′-fluorokanamycin A and B

Abstract

4′-Deoxy-4′-fluorokanamycins A ( 17) and B ( 25) have been prepared through fluorinative ring-opening of the d- galacto-3′,4′-oxiranes ( 8 and 21) derived from kanamycin A and B with potassium hydrogenfluoride in ethane-1,2-diol. The mechanism of preponderant formation of the 4′-deoxy-4′-fluoro- d-gluco ( 9 and 22) over the 3′-deoxy-3′-fluoro- d-gulo derivatives was discussed. In the synthesis of 25, the unusual 3′,6′-epimine ( 23) was the main product along with the 4′-deoxy-4′-fluoro derivative. The mechanism of this reaction is also discussed. Both 17 and 25 were active against resistant bacteria producing aminoglycoside-adenylylating enzymes for HO-4′.