Synthesis of an α-mycolic acid from Mycobacterium brumae containing a cis-alkene and an α-methyl-trans-alkene
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Al Araj Intisarthesis PhD 2018.pdf
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Abstract
Mycolic acids are high molecular weight α-alkyl-branched β -hydroxy long chain fatty acids (60-90 carbon atoms). Different species of Mycobacteria may produce different classes of mycolic acids including α-, methoxy and keto mycolic acids, each present as mixtures of homologues. These may also contain different functional groups such as ester, keto, methoxy, hydroxyl, and alkene groups. Mycolic acids and their trehalose esters are very important components of the mycobacterial cell wall. They show very interesting toxic and immunological properties; these offer considerable potential for application in the detection, control, and treatment of mycobacterial infection, and also in developing new methods for the detection of disease. The first part of this project involved the development of a new method for the synthesis of the α- alkyl-β-hydroxy fragment of mycolic acids, which required fewer steps compared to previous syntheses and used L-malic acid as starting material. The second part was to synthesise cis-alkene-α-methyl-trans-alkene mycolic acid (A), which contains a double bond at the distal and proximal positions. This type of mycolic acid has been isolated from Mycobacterium brumae. The third part of the project included the preparation of a number of sugar and glycerol esters of mycolic acid (A). These included the GroMM (B), GMM (C), the arabino-MA fragment from AG (D) and the trehalose esters TDM (E) and TMM (F). The final part of the project involved the synthesis of a different kind of fatty acid: the methyl esters of cyclopropene fatty acids, such as α-methoxy cyclopropane fatty acid (G). These compounds have been tested and were shown to inhibit Toxoplasma gondii growth in vitro, with compound (G) being the most effective.
Details
Original language | English |
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Award date | Jan 2018 |