COMPETITIVE-INHIBITION OF GLYCOSIDE HYDROLASES BY 1,3-DIAMINO-1,3-DIDEOXY-TETRITOLS AND THEIR CYCLIC CARBONIC AND THIOCARBONIC AMIDES

1,3-Diamino-1,3-dideoxy-D-threitol (1) and the corresponding 1,3-diami no-1,3-dideoxy-D-erythritol (2) were synthesised starting from D-gluco se and L-arabinose, respectively. These acyclic diamines inhibited com petitively both beta-D-glucosidase from sweet almond emulsin and beta- D-galactosidase from E. coli with K-1-values ranging from 3 to 10 mM. When the suitably blocked diamines were reacted with activated carboni c and thiocarbonic acid derivatives, cyclic urea droxy-4(R)-hydroxymet hyl-tetrahydropyrimidin-2-one (13), droxy-4(R)-hydroxymethyl-tetrahydr opyrimidin-2-one (15) and thiourea xy-4(R)-hydroxymethyl-tetrahydropyr imidin-2-thione (18) derivatives were obtained, which conformationally resemble the envelope structure of the D-glucopyranosyl or the D-gala ctopyranosyl cation. The cyclic carbonamides showed extremely weak com petitive inhibition but only with their corresponding enzymes. Compoun ds 15 and 18 exist, as indicated by H-1 NMR spectroscopy, in an unexpe cted E-conformation with axial substituents. Upon per-O-acetylation th e expected conformation with equatorial substituents is adopted.