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

具有药用价值的新生物活性化合物的合成是一个持续的挑战，对于寻找癌症、心血管疾病和其他医院感染的新治疗方法至关重要。显示出对这些疾病有用的生物学性质的大多数化合物具有杂环或多环骨架，例如泼尼松、贝壳杉烷衍生物、奈布林碱、芬得来定、来复新、东莨菪碱、劳伦烯酮或hispidospermidin。不幸的是，这些产品的天然量通常很低，需要破坏生态系统才能为患者提供治疗。因此，开发新的合成方法以快速获得这些结构是极其重要的。在这种情况下，本提案中提出的研究计划致力于开发符合umpolung概念的新方法，并涉及环境友好的高价碘试剂。在第一部分中，我们建议开发前所未有的氧化碳-碳形成介导的烯醇醚，不对称催化过程，有效地desymetrize前手性二烯酮系统或氧化polycyclisation方法的快速访问的详细结构。这些方法符合“绿色化学”的概念。这些转化的目的是获得可快速用于天然产物全合成的有价值的支架。在第二部分中，我们计划实现一些列举的目标，其化学结构可以快速复制与我们的方法的合成。该研究计划提供的结果应有助于通过发现应用于直接合成生物活性产品的不同新方法来促进知识进步。大多数生成的结构可以用于药物开发。此外，通过该计划培训的学生有可能为具有健康效益潜力和中长期加拿大工业影响的开创性研究做出贡献。

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.