Date of Award
Doctor of Philosophy
Biochemistry, Biophysics and Molecular Biology
Several analogues of sucrose were synthesized and tested as inhibitors of dextransucrase. These compounds were as follows: xylsucrose, (alpha)-D-xylopyranosyl fluoride, 6,6'-dideoxy-6,6'-dibromosucrose, 6,6'-dideoxy-6,6'-dichlorosucrose, 6,6'-dideoxy-6,6'-difluorosucrose, 6-deoxy-6-fluorosucrose and 6'-deoxy-6'-fluorosucrose. The last three of which are novel compounds;Xylsucrose was synthesized by the action of levansucrase on a mixture of raffinose and xylose where the raffinose is the fructofuranosyl donor and xylose is the acceptor; (alpha)-D-xylopyranosyl fluoride was synthesized by treating (beta)-D-xylopyranosyl tetraacetate with liquid hydrogen fluoride followed by a deacetylation using sodium methoxide;6,6'-Dideoxy-6,6'-dibromosucrose was prepared by treating sucrose with triphenylphosphine and carbon tetrabromide in anhydrous pyridine;6,6'-Dideoxy-6,6'-dichlorosucrose was prepared in a manner analogous to the preparation of 6,6'-dideoxy-6,6'-dibromosucrose;6,6'-Dideoxy-6,6'-difluorosucrose was prepared as the major component by treating 2,3,4,3',4'-penta-O-benzoylsucrose with a relatively mild fluorinating agent N,N-diethylamino-sulfur trifluoride (DAST) followed by debenzoylation in methanol with sodium methoxide. Despite the fact that there are three possible fluorination sites, only two react under the conditions of the reaction;6-Deoxy-6-fluorosucrose and 6'-deoxy-6'-fluorosucrose were prepared as a mixture from a mixture of 2,3,4,3',4',6'-hexa-O-benzoylsucrose and 2,3,4,6,3',4'-hexa-O-benzoylsucrose by treatment with DAST followed by debenzoylation using sodium methoxide in methanol. Each of these substances was characterized by ('13)C-NMR and ('19)F-NMR spectra when applicable in addition to various chromatographic data;In addition to these substances, a mixture of materials resulting from an attempt to synthesize fluorinated analogues using potassium fluoride as the fluorinating reagent, proved to be a very potent inhibitor of dextransucrase. Along with the sucrose analogues, two other materials proved to be inhibitors of dextransucrase, namely bacitracin and zinc chloride;Physical data are presented on all the substances in the form of NMR spectra (('13)C, ('19)F) and chromatographic data. Some of these materials probably accomplish the inhibition of dextransucrase through their ability to act as alkylating agents, others as glycosylating agents and others by forming a covalent dead-end complex with the enzyme.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
John Nicholas Zikopoulos
Zikopoulos, John Nicholas, "Chemical synthesis of sucrose analogues and the study of their inhibition of dextransucrase " (1980). Retrospective Theses and Dissertations. 6778.