Methyl amino-deoxy-glycosides with α- and β-gluco, α-galacto, or α-manno stereochemistry with the amino functionality in each of the four possible non-anomeric positions have been synthesized and their pK(a) values determined by titration. These model compounds were chosen because they are the amino derivatives of the most common glycosyl acceptors. From this study it was possible to evaluate the electron density at each of the given positions in the carbohydrate and compare them. Some general trends were observed: The basicity of the amino groups decreases in the order 6-NH(2)>3-NH(2)>2-NH(2)>4-NH(2) (referring to the position). The basicity of a of an amino-deoxy-sugar generally increases when one or more substituents on the sugar ring are axial. The basicity decreases when the amine is antiperiplanar to an oxygen atom. These findings are in agreement with the observations obtained from glycosylation chemistry and the regioselective protection of sugars.

N-alkylated analogues of 1-deoxynojirimycin inhibit β-glucosidase from white rot fungus. The amino group in the β-glucosidase–iminosugar complex is unprotonated when bound, while an active site carboxylate is protonated.

No abstract

Four substituted cis and trans-4,5-dihydroxyhexahydropyridazines that were expected to undergo pH induced conformational switching were synthesized and carefully investigated by NMR analyses and calculations. For two of the compounds a large difference in pKa existed between the two possible chair conformers and for one compound this resulted in conformational switching as a result of pH change. For the first time it is shown that the pKa directly reflects the conformational equilibrium of conformers.