Competitive inhibition of glycoside hydrolases by 1,3-diamino-1,3-dideoxy-tetritols and their cyclic carbonic and thiocarbonic amides

Article abstract of DOI:10.1016/0008-6215(93)84152-V

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 β-D-glucosidase from sweet almond emulsin and β-D-galactosidase from E. coli with K_i-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 1H NMR spectroscopy, in an unexpected E-conformation with axial substituents.Upon per-O-acetylation the expected conformation with equatorial substituents is adopted.