Synthesis of 3′-Deoxykanamycin B (Tobramycin)

Abstract

Abstract 3′-Deoxykanamycin B (tobramycin) was prepared from kanamycin B. 3′,4′:4″,6″-Di-O-cyclohexylidene derivative (2) of penta-N-ethoxycarbonylkanamycin B was 2″-O-benzoylated and the 3′,4′-O-cyclohexylidene group was selectively and quantitatively removed by treatment with 1 mol equivalent of water in N,N-dimethylformamide (DMF) to give the de-3′,4′-O-cyclohexylidene derivative (4). Regioselective tosylation in pyridine at −20 °C gave the 3′-O-tosyl derivative (5) in 70% yield. Despite the 1,3-diaxial interaction in the transition state, replacement of the tosyl group with iodide was successfully performed in high yield with NaI in DMF. Hydrogenolysis of the iodo derivative (6) and subsequent removal of the protecting groups gave 3′-deoxykanamycin B (10) in ≈25% overall yield from kanamycin B. Confirmation of the 3′-deoxy group was performed by measurement of Δ[M]TACu of 3′-deoxyneamine which was obtained from 10 by hydrolysis.