Title:

Non-enzymic Fluoride Elimination and Iodination of the Breslow Intermediate

Author: Wu, Lu-Tse
Advisor: Kluger, Ronald
Department: Chemistry
Issue Date: Nov-2017
Abstract (summary): 3-fluoropyruvate is an unusual substrate for pyruvate decarboxylase and pyruvate dehydrogenase that results in mechanistic divergence through exclusive fluoride elimination. A synthetic analogue, 2-(1-hydroxytrifluoroethyl)-thiamin (HTFETh), was designed to generate a similar Breslow intermediate to that produced in the diverted pathway. 1H NMR studies on HTFETh at pH/pD 7.0 displayed 100% fluoride elimination in solution and the corresponding C2alpha carbanion/enamine is subject to rapid proton transfer. The rate constants for C2alpha proton transfer were measured by trapping the Breslow intermediate with triiodide at various concentrations for the purpose of solving that of fluoride elimination. The results suggested that fluoride elimination is molecularly intrinsic and likely rate-determining on the enzymes. Furthermore, the second-order rate constants for C2alpha proton transfer showed general base and general acid catalysis and an averaged pKa value of 12.5. Preliminary Brønsted plots with alpha = 0.48 and beta = 0.49 implied mid-way proton transfer at the transition state.
Content Type: Thesis

Permanent link

https://hdl.handle.net/1807/79102

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