Studies on cyclitols—XII : New syntheses of 2-deoxystreptamine and triaminocyclohexanediols

Abstract

The previously reported method for conversion of cyclopentanoid cyclitols into cyclohexanoid aminocyclitols has been applied to (1,2/3,5)-3,5-diacetamidocyclopentane-1,2-diol 4a, to produce acetylated derivatives of (1,3/2,4,6)-4,6-diaminocyclohexane-1,2,3-triol(deoxystreptamine) 24, the epimeric (1,2,3/4,6)-diaminotriol 9 and the corresponding 2,4,6-triaminocyclohexane-1,3-diols 11 and 10. The well known cis-3,5-dibromo-1-cyclopentene 1was converted by treatment with sodium azide into cis-3,5-diazido-1-cyclopentene 2; oxidation of 2 with KMnO 4 gave(1,2/3,5)-3,5-diazidocyclopentane-1,2-diol 3a, which was acetylated to the di-O-acetyl derivative 3b. Hydrogenation with Pd-C catalyst and acetylation gave (1,2/3,5)-3,5-diacetamido-1,2-di-O-acetylcyclopentane-1,2-diol 4b and selective deacetylation with methanolic NH 3 gave the diacetamidodiol 4a. The NMR spectra of 2, 3b and 4b were consistent with the proposed structures. Oxidation of 4a with periodate gave erythro-2,4-diacetamidocyclopentanedial 5 which was treated with nitromethane under alkaline conditions to give a mixture of diacetamidonitrocyclohexanediols whose principal components were (1,3/2,4,6)-4,6-diacetamido-2-nitrocyclohexane-1,3-diol 6a and the epimeric (1,2,3/4,6) compound 7a. Hydrogenation of 6a with Raney nickel T4 catalyst gave (1,3/2,4,6)-4,6-diacetamido-2-aminocyclohexane-1,3-diol 8, which was acetylated to (1,3/2,4,6)-2,4,6-triacetamido-1,3-di-O-acetylcyclohexane-1,3-di 11b; the NMR spectrum of 11b showed the presence of 3 equatorial acetamido groups, two of which are isochronous, and two equivalent equatorial acetoxyl groups. Selective acetylation of 8 gave (1,3/2,4,6)-4,6-diacetamido-1,3-di-O-acetyl-2 aminocyclohexane-1,3-diol 11d. Treatment of the hydrochloride (or hydrobromide) of both 8 and 11d with AgNO 2 and acetylation of the deaminated product gave ( 1,2,3/4,6)-4,6-diacetamido-1,2,3-tri-O-acetylcyclohexane-1,2,3-triol 9c. The NMR spectrum showed the presence of two isochronous equatorial acetamido groups, two isochronous equatorial acetoxyl groups and one axial acetoxyl group. Hydrogenation of 7a followed by acetylation gave (1,2,3/4,6)-2,4,6-triacetamido-1,3-di-O-acetylcyclohexane-1,3-diol 10c; the NMR spectrum of 10c showed the presence of two isochronous equatorial acetamido groups, one axial acetamido group and two isochronous equatorial acetoxyl groups. Confirmation of some of the configurational assignments was obtained when di-N-acetyldeoxystreptamine 24a was oxidized by periodate to give a diacetamidopentanedial which was proved to be identical with 5 when it reacted with nitromethane to give the same cyclohexanoid products. When 11d was deaminated as described and the product treated with CrO 3, a ketonic compound (1,3/4,6)-4,6-diacetamido-1,3-di-O-acetyl-2-oxocyclohexane-1,3-diol 25 was obtained; reduction of 25 with NaBH 4 and acetylation of the product gave a mixture of pentaacetyl deoxystreptamine 24b and the epimeric compound 9c. By the use of 14CH 3NO 2, 10c and 11b specifically labeled in carbon-2 were obtained.