Synthetic studies towards the fimbrolides and AHL autoinducers [thesis]

William Lao
This thesis has three major parts, all dealing with the chemistry of fimbrolides, a class of halogenated lactones derived from the red marine algae, Delisea pulchra. Part 1 concerns the evaluation, adaptation and modification of existing synthetic fimbrolides in an attempt to improve accessibility to these compounds and their analogues. The focus of one such modification was the introduction of oxygen into the fimbrolide sidechain. Construction of a functionalized allene ester precursor through
more » ... incorporation of the Baylis-Hillman reaction was not successful because a competing isomerisation reaction took place. However allene esters were shown to provide iodoand bromo-substituted furanones. Direct oxygenation at the allylic position of a preformed fimbrolide sidechain did not provide any success. Treatment with a variety of oxidizing agents gave either no reaction or degradation to intractable products. Another modification began from a furan aldehyde, involved organometallic addition to the aldehyde group, followed by oxidation and introduction of the halogenated exocyclic double bond, another important aspect of fimbrolides. This synthetic route not only provided a route towards natural fimbrolides, but also possessed the possibility of preparing analogues of the naturally occurring substances, such as a two carbon length side chain variety, and those with modified exocyclic double bonds. Part 2 is relatively short and is concerned with methods of attaching and delivering biologically active fimbrolides for application purposes. The investigation involved the conversion of fimbrolide alcohols into functional ester derivatives and monomers for incorporation into polymers. An unexpected conversion of one alcohol into the corresponding acetamide derivative, through a Ritter reaction, was observed and this might provide opportunities in the future for similar transformations.
doi:10.26190/unsworks/7061 fatcat:wks25ykol5dp5oc2nzbi7jd6iq