A chiral approach to 2-deoxystreptamine

Abstract

A new synthesis of 2-deoxystreptamine (21), a component of numerous antibiotics, was developed. Starting from D-mannose, it proceeds through chiral intermediates and is designed to furnish starting points for the preparation of stereospecifically modified derivatives of the meso compound 21. 1,2-Dideoxy-1-nitro-D-manno-heptitol (2), obtainable from mannose by the nitromethane method, was protected as the 4,5:6,7-di-O-isopropylidene derivative 4, which was mesylated or triflated in position 3. From the sulfonic esters (5 and 6) two different routes involving displacement by azide, partial deacetonation at O-6,7, periodate oxidation, and cyclization of the resulting nitroaldohexose derivatives converged to give 1L-(1,3/2,4,6)-6-azido-1,2-O-isopropylidene-4-nitro-1,2,3-cyclohexanetriol (19) as a key intermediate. Catalytic hydrogenation then afforded optically active 4,5-O-isopropylidene-2-deoxystreptamine (23), isolated as its N,N′-diacetyl derivative 24. Deacetonation of 19 gave the azidonitrotriol 15, which was reduced to 21. The potential utility of the chiral intermediates for stereospecific syntheses of deoxystreptamine-containing aminoglycosides is discussed.