Aromataic ring umpolung: developments and key applications in total synthesis of several natural products

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Synthesis of new bioactive compounds of pharmaceutical interest represents a continuing challenge and is crucial for finding new treatments for cancer, cardiovascular diseases and other nosocomial infections. Most of the compounds demonstrating useful biological properties against these diseases possess a heterocyclic or a polycyclic skeleton such as prednisone, kaurane derivatives, neblinine, fendleridine, lycoflexine, scopaldulcic acid, laurencenone or hispidospermidin. Unfortunately, the natural amount of these products is generally low and would require damaging an ecosystem to provide treatment to patients. Consequently, it is extremely important to develop new synthetic methods to obtain these structures quickly. In this context, the research program presented in this proposal is dedicated to the development of novel methodologies fitting within the umpolung concept and involving environmentally benign hypervalent iodine reagents. In a first part, we propose to develop unprecedented oxidative carbon-carbon formations mediated from enol-ethers, an asymmetric catalytic process to desymmetrize efficiently prochiral dienone systems or an oxidative polycyclisation method for the rapid access of elaborated structures. These methods are in agreement with the concept of "green chemistry". The aim of these transformations is to get valuable scaffolds that could be rapidly used in total synthesis of natural products. In a second part, we plan to achieve the synthesis of some of the enumerated targets, whose chemical structures could be quickly reproduced with our methodologies. Results afforded by this research programme should contribute to the knowledge advancement by the discovery of different novel methodologies applied to the direct synthesis of bioactive products. Most of the structures generated could be tested for pharmaceutical developments. In addition, students trained through this program are likely to contribute to ground breaking research with health benefit potential and medium- to long-term Canadian industrial impact.