The design and synthesis of novel potential antimalarial compounds

• Main Author: Villa, Mathew V. J.
• Published: University of Glasgow 2009
• Subjects: 615.1; QD Chemistry
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.495362

The work contained in this thesis is split into two sections. Each section covers a different biological pathway, its current importance as a potential drug target, and the syntheses towards a selection of natural products and analogues relevant to the pathway. In Section A, the novel approach towards a new class of n-formyl amides is described. Furthermore, this new methodology is used to generate the imide intermediate A1. This imide is now considered a key intermediate in our synthesis of natural products CJ-15,801, Pantothenate, and the first generation of analogues based on CJ-15,801. This section also covers the potential scope for n-formyl imides in chemical synthesis in general. Section B describes two novel approaches towards non-mevalonate pathway (MEP) intermediates and inhibitors. The synthesis towards a previously unpublished 2,2-dimethyl MEP analogue, is described alongside the attempted generation MEP. The methodology described herein shows the use of Neighbouring Group Participation in intramolecular opening of epoxides, and how this can be applied to the generation of analogues. Above all, the aim of this thesis is to open up new synthetic strategies towards potential inhibitors for individual biosynthetic pathways.