On the total synthesis of terpenes containing quaternary stereocenters: Stereoselective synthesis of the taiwaniaquinoids, mastigophorene A, and tuberculosinyl adenosine

In this dissertation the stereoselective synthesis of several natural products is reported. First mycoketide was constructed and analyzed using NMR spectroscopy in order to establish a predictive model for natural products bearing a 1,5-methyl ramification. The following two chapters describe our venture, in collaboration with the Moody laboratory (Harvard medical school), into the synthesis of 1-tuberculosinyl adenosine (1-TbAd). This molecule was isolated from Mycobacterium tuberculosis and found to be specific to the organism. Additionally 1-TbAd was found to be produced by the virulence associated enzyme Rv3378c which makes 1-TbAd a suspect for promoting virulence. The synthesis of 1-TbAd provided material which was used in the development of a chemical marker for the tuberculosis disease. More material was produced in the first, multi-gram, stereoselective synthesis of 1-TbAd. Besides its synthesis we also investigated, by means of in silico studies, the stereoselective Diels-Alder reaction used to introduce the chiral centers.
The second half of this PhD thesis focused on the Pd-catalyzed asymmetric synthesis of benzylic quaternary stereocenters, by means of a conjugate addition, utilizing ortho-substituted arylboronic acids. First the reaction was developed and applied in the shortest stereoselective syntheses of herbertenediol, and enokipodin A and B. In the following chapter the development of the Pd-catalyzed homo-coupling of aryllithium reagents is described with direct application in the shortest asymmetric synthesis of mastigophorene A. The thesis finishes with an investigation into the synthesis of the taiwaniaquinoid family.