Synthesis of 4-deoxy-D-xylo-hexose and 4-azido-4-deoxy-D-glucose and their effects on lactose synthase.
Syntheses are reported of 4-deoxy-D-xylo-hexose and 4-azido-4-deoxy-D-glucose as potential inhibitors for lactose synthase [uridine 5'-(alpha-D-galactopyranosyl pyrophosphate):D-glucose 4-beta-D-galactopyranosyltransferase, EC 2.4.1.22]. These syntheses involved SN2 displacement of the 4-methylsulfonyloxy group of methyl 2,3,6-tri-O-benzoyl-4-O-methylsulfonyl-alpha-D-galactopyranoside by iodide and azide ions. In both cases, inversion in configuration was observed. The resulting intermediates, methyl 2,3,6-tri-O-benzoyl-4-deoxy-4-iodo-alpha-D-glucopyranoside and methyl 4-azido-2,3,6-tri-O-benzoyl-4-deoxy-alpha-D-glucopyranoside, were obtained in crystalline form. Both 4-deoxy-D-xylo-hexose and 4-azido-4-deoxy-D-glucose were found to be inhibitors for lactose synthase in the presence of alpha-lactalbumin, but had no effect in the absence of alpha-lactalbumin. Both D-glucose analogues bind to the enzyme system far more weakly than D-glucose, suggesting that the recognition of the 4-OH group of the acceptor substrate is an important factor in binding.
D000818:Animals; D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology; D002417:Cattle; D003126:Colostrum / Q000201:enzymology; D003837:Deoxy Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D003847:Deoxyglucose / Q000138:chemical synthesis* / Q000494:pharmacology / Q000031:analogs & derivatives; D005260:Female; D005700:Galactosyltransferases / Q000378:metabolism; D007700:Kinetics; D007788:Lactose Synthase / Q000037:antagonists & inhibitors*; D008722:Methods; D011247:Pregnancy; D013329:Structure-Activity Relationship
D001386:Azides; D003837:Deoxy Sugars; C025556:4-azido-4-deoxyglucose; C025557:4-deoxy-D-xylo-hexose; D003847:Deoxyglucose; D005700:Galactosyltransferases; D007788:Lactose Synthase