Enantiospecific syntheses of (+)-hyosamine and (-)-hyosamine, and stereospecific glycosylation of 2-deoxystreptamine.

Abstract

Two aminocyclitol antibiotics, hygromycin B and destomycin A, contain as a structural component optically active N-methyl(1,3/2,4,6)-4,6-diamino-1,2,3-trihydroxycyclohexanetriol (hyosamine). The (+)-enantiomer is present in the former antibiotic, and the ($-$)-enantiomer, in the latter. The present work describes enantiospecific syntheses of these two components, starting from a common chiral precursor, 1 scL-(1,3/2,4,6)-6-azido-1,2-O-isopropylidene-4-nitro-1,2,3-cyclohexanetriol. The precursor was prepared in 9 steps from scD-mannose according to a recently published procedure. Different sequential manipulations of its two unequal nitrogenous functions, converting these eventually into an amino and an N-methylamino group, led to the target compounds in enantiospecific fashion. Several approaches were explored, and one approach to (+)-hyosamine and two to ($-$)-hyosamine were successful. The above mentioned azidonitro precursor was also used for a synthesis of a blocked derivative of 2-deoxystreptamine (1,3-diamino-4,5,6-trihydroxycyclohexane) stereospecifically glycosylated in the 6-position. This was accomplished by conversion of the blocked azidonitrocyclitol into the corresponding diacetamido compound and coupling with acetobromoglucose.