A novel synthesis of bacterial autoinducer DPD and approaches towards its fluoro-analogues

UoM administered thesis: Master of Philosophy

  • Authors:
  • Fariba Fanimarvasti

Abstract

(S)-4,5-Dihydroxypentane-2,3-dione ((S)-DPD) is a signaling molecule for the inter- and intra-species bacterial communication called quorum sensing. Although DPD is a simple molecule, it is highly reactive and functionalized, and therefore complicated to synthesize. The aims of this research were to develop a novel synthesis of (S)-DPD, and to synthesize the fluoro-analogues of (S)-DPD, with the replacement of one or both of the hydroxyl groups with fluorine. (S)-DPD and its fluoro-analogues will be of use in microbiology studies to investigate their biological activities and potentially find a lead for the development of novel anti-bacterials.A novel synthesis of (S)-DPD was developed, starting from a commercially available chemical, L-gulonic acid-γ-lactone, which underwent protection and oxidation, followed by a Wittig reaction, dihydroxylation and oxidation to give (S)-DPD.In an attempt to prepare the fluoro-analogues of DPD, three pathways were designed. Pathway 1 started from D-mannitol using a Wittig reaction to give an alkene diol, (S, E)-Pent-3-ene-1,2-diol, which was the precursor for the fluorination steps. Fluorination of the alkene diol with XtalFluor-E failed to give the desired compounds and pathway 1 was discontinued.Pathway 2 was developed to produce an alkyne diol, (S)-Pent-3-yne-1,2-diol, from D-mannitol, the key step involving a Corey-Fuchs reaction. The very low yield of the alkyne diol led to the termination of the pathway 2.Pathway 3 started from L-gulonic acid-γ-lactone protected by the cyclohexylidene protecting group. The alkyne diol, (R, E)-Pent-3-ene-1,2-diol, was formed in a moderate yield, but its fluorination with XtalFluor-E to make the corresponding fluoro-alkyne (S)-4,5-difluoropent-2-yne failed. Although the syntheses of the fluoro-analogues of DPD have not been achieved, several novel precursors have been prepared and modification of their fluorinating conditions may yield these analogues.

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Original languageEnglish
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Award date31 Dec 2011