Chemical and enzymic studies of carbohydrate oximes

Abstract

The oximes of D-arabinose, D-galactose, B-mannose and D-ribose have been synthesised and their structures determined in the solid state and in solution by a variety of chemical and physical methods. These carbohydrate oxirnes can exist in the acyclic anti(z) or syn(E) form in the solid state, and isomerise to a mixture of anti(Z, 20%) and syn(E, 80%) forms in aqueous solution. B-glucose oxime exists in the cyclic beta-pyranose form in the solid state and equilibrates to a mixture of beta-pyranose (23%), beta-pyranose (7%), syn(E, 56.5%) and anti(Z, 13.5%) forms in solution. The interconversion of carbohydrate oximes in aqueous solution was studied and found to be simple (first order) except for B-glucose oxime which showed complex isomerisation kinetics. The simple (first order) isomerisation of B-arabinose oxime was shown to be subject to specific and general acid, and specific base catalysis. B-Arabinose oxime has been shown to act as a substrate of yeast hexokinase, the product B-arabinose oxime-5-phosphate (lithium salt) has been isolated and characterised. This result together with observations of the interaction of other carbohydrate derivatives has allowed the current picture of the substrate specificity of this enzyme to be extended. By application of transition state theory carbohydrate oximes are predicted to act as inhibitors of enzymes which catalyse the interconversion of aldoses and ketoses. This prediction has been confirmed in the case of B-:xylose (B-glucose) isomerase (Streptomyces species), of which B-arabinose and B-glucose oximes are more powerful inhibitors than other compounds previously examined.