Synthesis of 1d-(1,3,5/2,4)-4-acetamido-5-amino-1,2,3-cyclohexanetriol and its incorporation into a pseudo-disaccharide

The synthesis of the title compound and 1d-(1,3,5/2,4)-4-acetamido-5-amino-3-O-(β-d-glucopyranosyluronic acid)-1,2,3-cyclohexanetriol is described. Starting from methyl 2-acetamido-2-deoxy-α-d-glucopyranoside 2l-(2,4,5/3)-4-acetamido-3-benzoyloxy-2-benzyloxy-5-hydroxycyclohexanone was prepared via a series of transformations including the regioselective ring opening of the benzylidene acetal and the mercury(II)-catalyzed carbocyclic ring closure reaction of 5-enopyranoside. Stereoselective reduction of ketone 11 with NaBH(OAc)3 gave 1d-(1,2,4/3,5)-2-acetamido-3-O-benzoyl-4-O-benzyl-1,3,4,5-cyclohexanetetrol (88%), which was then converted into 1d-(1,3,5/2,4)-4-acetamido-5-azido-3-O-benzoyl-2-O-benzyl-1-O-pivaloyl-1,2,3-cyclohexanetriol through selective 5-OH protection, 1-O-mesylation, and subsequent azide displacement. Saponification and hydrogenation of this gave the title compound. Selective O-debenzoylation with 1.1 equiv of K2CO3 in MeOH gave 1d-(1,3,5/2,4)-4-acetamido-5-azido-2-O-benzyl-1-O-pivaloyl-1,2,3-cyclohexanetriol (73%). Glycosylation of this compound with methyl (2,3,4-tri-O-acetyl-α-d-glucopyranosyl bromide)uronate in CH2Cl2, using silver triflate as the promoter, afforded 1d-(1,3,5/2,4)-4-acetamido-5-azido-2-O-benzyl-3-O-(methyl 2,3,4-tri-O-acetyl-β-d-glucopyranosyluronate)-1-O-pivaloyl-1,2,3-cyclohexanetriol (20) in 79% yield. Finally, O-deacylation and subsequent hydrogenation of this compound gave the basic pseudo-disaccharide.