ANALOGS OF DISACCHARIDES AND GLYCOSIDES CONTAINING A CYCLIC GUANIDINIUM STRUCTURE SHOW VARYING INHIBITORY EFFECTS ON GLYCOSIDE HYDROLASES

By condensation of ino-2,4-(R)-O-benzylidene-1,3-dideoxy-D-erythritol (3) and 1,3-diamino-2,4-di-O-benzyl-1,3-dideoxy-D-threitol (4) with me thyl yl-4-deoxy-4-isothiocyanato-beta-D-glucopyranoside (9) the (1 --> 4)-linked disaccharide analogues dropyrimidin-2-yl]amino-alpha,beta-D -glucopyranose hydrochloride (15) and dropyrimidin-2-yl]amino-alpha,be ta-D-glucopyranose hydrochloride (18) were synthesized. By the same re action sequence, using 3 and methyl isothiocyanate, the glycoside anal ogue (4R,5S)-5-hydroxy-4-(hydroxymethyl)-2-methylamino- 1,4,5,6-tetrah ydropyrimidine hydrochloride (20) was obtained. All compounds possess in their 'glyconic' moiety the flat guanidinium group, mimicking a glu copyranosyl cation. Together with the previously synthesized (1 --> 6) -linked disaccharide analogues dropyrimidin-2-yl]amino-alpha,beta-D-gl ucopyranose hydrochloride (I) and dropyrimidin-2-yl]amino-alpha,beta-D -glucopyranose hydrochloride (2), a possible inhibitory effect on the action of alpha-D-glucosidase, beta-D-glucosidase, cu-D-galactosidase, and beta-D-galactosidase was investigated. All compounds, except 20 w ith alpha-D-glucosidase where no inhibition could be detected, showed either competitive or mixed competitive inhibition with all enzymes. T he effects of the disaccharide analogues were generally weaker as comp ared to the effect of the previously synthesized configurationally rel ated nitrophenyl glycoside analogues (4R,SS)-5-hydroxy-4-(hydroxymethy l)-2-(p hydrochloride (21) and (p-nitrophenyl)amino-1,4,5,6-te-trahydr opyrimidine hydrochloride (22). On the basis of experimental results, different binding modes of competitive inhibitors to the active site o f corresponding enzymes are discussed.