Date of Award


Publication Type

Doctoral Thesis

Degree Name



Chemistry and Biochemistry


Chemistry, Biochemistry.




In Part I, a rationale for the synthesis of 4-deoxy-4-fluoro-D-fructose using a combination of chemical and enzymic methods is proposed and undertaken. Partially purified pyranose-2-oxidase (E.C. is isolated from mycelia of Polyporus obtusus and a study of the enzyme specificity undertaken. Pyranose-2-oxidase is specific for the oxidation of glucose to D-arabino-hexos-2-ulose (D-glucosone) with a Km value of 3.2 (+OR-) 0.08mM and a Vmax of 126 (+OR-) 0.02(mu)mol min('-1) mg protein('-1). In contrast, 3-deoxy-3-fluoro-D-glucose is not a substrate for the enzyme. 4-Deoxy-4-fluoro-D-glucose, however, does act as a substrate with a Km value of 5.54 (+OR-) 0.64mM and a Vmax of 104 (+OR-) 0.07(mu)mol min('-1) mg protein('-1) and as competitive inhibitor of glucose with a Ki value of 5.5 (+OR-) 0.02mM. Pyranose-2-oxidase is immobilized with activated Sepharose 4B and the product of oxidation of 4-deoxy-4-fluoro-D-glucose isolated and characterized as 4-deoxy-4-fluoro-D-arabino-hexos-2-ulose (1). Catalytic hydrogenation of (1) yields 4-deoxy-4-fluoro-D-fructose (2). Both (1) and (2) are characterized by infra red, ('19)F NMR and mass spectrometry. The structure of (2) is confirmed by sodium borohydride reduction. In Part II, the toxicity of 4-deoxy-4-fluoro-D-glucose in Locusta migratoria is studied and compared with that of 3-deoxy-3-fluoro-D-glucose. 4-Deoxy-4-fluoro-D-glucose is found to be more toxic than 3-deoxy-3-fluro-D-glucose. LD(,50) for 4-deoxy-4-fluoro-D-glucose is 0.6mg gm('-1) locust, compared with 4.8mg gm('-1) locust for 3-deoxy-3-fluoro-D-glucose. The formation of metabolites is established by HPLC analysis. One metabolite is identified as 4-deoxy-4-fluoro-D-glucitol. The toxicity of 4-deoxy-4-fluoro-D-glucose is associated with concomitant release of fluoride ion. It is suggested that the defluorination occurs at the point of action of aldolase, resulting in a glycolytic inhibition. A tentative mechanism for the action of the aldolase on the 4-deoxy-4-fluoro-D-glucose is presented.Dept. of Chemistry and Biochemistry. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1986 .S668. Source: Dissertation Abstracts International, Volume: 47-09, Section: B, page: 3756. Thesis (Ph.D.)--University of Windsor (Canada), 1986.