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-diamino-1,3-dideoxy-D-erythritol (2) were synthesised starting from D-glucose and L-arabinose, respectively. These acyclic diamines inhibited competitively 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 carbonic and thiocarbonic acid derivatives, cyclic urea 5(R)-hydroxy-4(R)-hydroxymethyl-tetrahydropyrimidin-2-one (13), 5(S)-hydroxy-4(R)-hydroxymethyl-tetrahydropyrimidin-2-one (15) and thiourea 5(S)-hydroxy-4(R)-hydroxymethyl-tetrahydropyrimidin-2-thione (18) derivatives were obtained, which conformationally resemble the envelope structure of the D-glucopyranosyl or the D-galactopyranosyl cation. The cyclic carbonamides showed extremely weak competitive inhibition but only with their corresponding enzymes. Compounds 15 and 18 exist, as indicated by H-1 NMR spectroscopy, in an unexpected E-conformation with axial substituents. Upon per-O-acetylation the expected conformation with equatorial substituents is adopted.