| There is a high level of overall global awareness of the mortality, morbidity and economic burden resulting from the lack of essential medicines in resource-poor settings.1 The World Health Organization (WHO) maintains an Essential Medicines List (EML; http://www.who.int/mediacentre/fact/sheet/fs094/en) including medicines for treating devasting diseases such as HIV/AIDS, malaria, and tuberculosis. International Donor Agencies supply medicines or funding to procure medicines to treat these "big three" diseases as well as opportunistic infections related to HIV/AIDS and maternal and fetal health.;Malaria is an infectious disease with an estimated annual incidence of approximately 235 million new infections. A series of drug combinations are recommended by the World Health Organization for the treatment of uncomplicated malaria. Specific combinations of a semi-synthetic derivative of artemisinin and a synthetic drug are preferred for this purpose. The combination [amodiaquine + artesunate] is one such priority treatment. Another combination is [dihydroartemisinin + piperaquine]. There is also a need for less expensive, reliable sources of artemisinin. My research has reconnoitered and developed new chemistries to address these needs.;There are currently over 30 antiretroviral (ARV) drugs approved for treatment of HIV/AIDS. Darunavir is a Protease Inhibitor drug important for the 2 nd line treatment of HIV/AIDS. The use of Darunavir greatly enhances the durability of 2nd line therapy and creates a high genetic barrier to the emergence of resistant viruses. It is estimated that 750,000 patients in developing countries will be on 2nd line HAART therapy by 2015. Synthesizing the core of this molecule with control of absolute stereochemistry is one key to reducing cost and increasing availability of this drug. Organocatalysis is increasingly being used to provide synthetic control via the aldol and Henry (e.g.) reactions.;My thesis describes the development of new, less expensive synthesis of the core of darunavir with comparison to atazanavir; as well as, the syntheses of artemisinin, piperaquine used in formulation of (DHAP) tablets in adult and pediatric forms, amodiaquine dihydrochloride dihydrate, and a new halofantrine synthesis to focus on a single enantiomer. This will decrease the cost and increase access to these drugs in Less-Developed Countries. |
