Mycobacteria are found in many environments. They have complex mixtures of
mycolic acids and lipids present in their cells wall. Mycolic acids are high molecular weight α-alkyl-branched β-hydroxy long-chain fatty acids. They have 60-90 carbon atoms. Different groups of mycolic acids are made by different species of mycobacteria. Sugar esters of mycolic acids which are associated with the cell wall have very interesting toxic and immunological properties. They also have the potential to assist in TB detection for development of sensors, which could be used for the control and treatment of mycobacterial infection. This research involved the synthesis of mycolic acids and trehalose esters. The biological activities were studied, as well as their suitability as antigens to detect mycobacterial infections. There were four objectives: The first part of this project involved the synthesis of saturated (A) and unsaturated (B) mycolic acids as occurring in Rhodococcus equi were achieved, and the synthesis of trehalose dimycolate (C), trehalose monomycolate (D) and glucose monomycolate (E) present in R. equi were also achieved. This was to study whether or
not the chain length has any effect on the biological activities in phagosomes-lysosome fusion assays.
The second part of this project involved the synthesis of two stereoisomers of the key homologue of the methoxy (F) and keto (G) mycolic acids present in Mycobacterium kansasii were achieved successfully, which were then coupled to trehalose to generate the corresponding synthetic trehalose dimycolate (H) and trehalose monomycolate (I). These methoxy mycolic acid and their corresponding trehalose esters would be used as a specific antigens to distinguish the Mycobacterium kansasii from Mycobacterium tuberculosis specifically in serodiagnostic assays (Enzyme-linked lmmunosorbent Assay).
The third part of this study involved the synthesis of sugar ester of the cis-cyclopropane methoxy mycolic acid of Mycobacterium tuberculosis with identical absolute stereo-chemistry to the natural compound, which were then coupled to trehalose to generate the corresponding synthetic trehalose dimycolate (J) and trehalose monomycolate (K). These trehalose esters would be used as a specific antigens in serodiagnostic assays (Enzyme-linked Jmmunosorbent Assay) for the detection of TB, will allow the effect of the stereochemistry of cis-cyclopropane on the assay to be investigated.
The fourth part of this study involved the synthesis of mixed sugar ester (K, L)
including two different classes of mycolic acids present in M kansasii and M
tuberculosis were achieved successfully. Natural TDM consists of a very complex mixture of different molecules made in a biological system where there are many different types and homologues of MA present; unless there is a specific biological control system that introduces the same MA on both sugar rings of the TDM, it is therefore very unlikely that natural molecules contain two identical MAs. Therefore it is important to prepare compounds of containing two different MA in order to investigate their biological activity and compare them to the TDMs that contain the same MA at both positions.