The design and synthesis of novel potential antimalarial compounds

QD Chemistry

Villa, Mathew V.J. ; Rodolfo, Marquez

University:University of Glasgow

Department:School of Chemistry

关键词: n-formyl amides, imide, CJ-15,801, Pantothenate, non-mevalonate pathway, MEP;   

Others  :  http://theses.gla.ac.uk/613/1/2009Villa1PhD.pdf

来源: University of Glasgow

【 摘 要 】

The work contained in this thesis is split into two sections.Each section covers a different biological pathway, its current importance as a potentialdrug target, and the syntheses towards a selection of natural products and analoguesrelevant 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. Thisimide 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 ingeneral.Section B describes two novel approaches towards non-mevalonate pathway (MEP)intermediates and inhibitors. The synthesis towards a previously unpublished 2,2-dimethylMEP analogue, is described alongside the attempted generation MEP. The methodologydescribed herein shows the use of Neighbouring Group Participation in intramolecularopening 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 potentialinhibitors for individual biosynthetic pathways.