Stereocontrolled synthesis of a thiolated mycolic acid for development of novel TB diagnostics

Abstract

The current global tuberculosis epidemic has shown the need to urgently replace the aged anti-TB armamentarium. The search for a fast, accurate and reliable diagnosis of active TB has emerged as the spearhead in efforts to defeat the scourge. Traditional diagnostics that have existed for more than a century are at best inadequate against the wilier modern forms of the disease like TB-HIV/AIDS co-infection and the drug resistant TB. The development of mycolic acid based serodiagnostics has introduced a powerful tool that gives high hopes of solving the diagnostic challenges of a large percentage of TB cases. To date, these biosensor-based technologies require the immobilization of MA antigens on a gold substrate for antibody recognition. Several challenges need to be resolved before these new technologies can be rolled out as affordable and reliable diagnostic tools. This project sets out primarily to economize the synthesis of MA and develop a new and stable antigenic surface that will improve reliability of tests. Chemical knowledge of MA has been growing over the past century but total organic synthesis of the various forms of these complex molecules have only been achieved in the past decade. This project focused on improving a recently developed synthetic route to the mycolic motif. It successfully scaled up the synthesis by systematically troubleshooting various aspects of the synthetic protocol. This resulted in the reduction of the number of reactions by at least 6 steps compared to the current literature method [Scheme I]. Importantly, this method has the potential of being extended to the synthesis of much longer fragments of the mycolic acid molecule.