Enzymic glycosylation of (+/-)-(3,5/4,6)-3,6-diazido-4,5- dihydroxycyclohexene. A way to prepare stereochemically pure and enzyme resistant, basic pseudo-disaccharides as competitive enzyme inhibitors.
By beta-D-galactosylation of (+/-)-(3,5/4,6)-3,6-diazido-4,5-dihydroxycyclohexene, pure (+)-3,5/4,6)-3,6-diazido-4-O-(beta-D-galactopyranosyl)-5-hydrox ycyclohexene (3) was obtained. The diamine (+)-(1,3/2,6)-3,6-diamino-1-O-(beta-D-galactopyranosyl)-2-hydroxycycl ohexane, derived from compound 3 by catalytic hydrogenation, is stable against enzymic cleavage and competitively inhibits beta-D-galactosidase from Escherichia coli with a Ki-value of 5.5 mM. Sigmatropic rearrangement of 3 in methanolic solution partially led to an unseparable mixture of the regioisomers (3,5/4,6)-3,4-diazido-5-O-(beta-D-galactopyranosyl)-6-hydroxycy clohexene and (3,5/4,6)-3,4-diazido-6-O-(beta-D-galactopyranosyl)-5-hydroxycy clohexene. Catalytic hydrogenation thereof yielded an equally unseparable mixture of the diamines (1,3/2,4)-1,2-diamino-4-O-(beta-D-galactopyranosyl)-4-hydroxycyclohex ane and (1,3/2,4)-1,2-diamino-4-O-(beta-D-galactopyranosyl)-3-hydroxycyclohex ane, inhibiting beta-D-galactosidase competitively with K(i) 0.9 mM.
Institut für Organische Chemie und Biochemie der Universität Freiburg, Germany.
J
J
Lehmann
B
B
Rob
D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry; D001667:Binding, Competitive; D002240:Carbohydrate Sequence; D003510:Cyclohexanes / Q000737:chemistry*; D053138:Cyclohexenes; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D006031:Glycosylation; D008969:Molecular Sequence Data; D013237:Stereoisomerism
D001386:Azides; D003510:Cyclohexanes; D053138:Cyclohexenes; D004187:Disaccharides; D004791:Enzyme Inhibitors; C052568:cyclohexene