Enantiospecific syntheses of (+)-hyosamine and (−)-hyosamine

Abstract

Two constituent components of the stereoisomeric aminocyclitol antibiotics hygromycin B and destomycin A, namely, (+)-hyosamine and (−)-hyosamine (1L- and 1D-(1,3/2,4,6)-4-amino-6-methylamino-1,2,3-cyclohexanetriol 1 and 2, respectively) were synthesized independently in enantiospecific fashion from the common preparative precursor 3, 1L-(1,3/2,4,6)-6-azido-1,2-O-isopropylidene-4-nitro-1,2,3-cyclohexanetriol, which is conveniently accessible from D-mannose. The key strategy involved selective and sequential reduction of the nitrogenous functions in 3 to the amino stage and installation of an N-methyl group in appropriately blocked derivatives. Several variations based on this principle were examined, and one approach to 1 as well as two approaches to 2 were successfully completed. The target amines were characterized as their crystalline penta-N,O-acetyl derivatives 12 and 22. Key words: aminocyclitol antibiotics, enantiospecific syntheses of hyosamines, nitrogen-substituted 1,2,3-cyclohexanetriols.