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

芳香环umpolung：几种天然产物全合成的进展和关键应用

• 批准号: 341582-2011
• 负责人: Canesi, Sylvain
• 金额: $ 2.55万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=572309
• 关键词: Aromataic; ring; umpolung; developments; key

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.

具有药学价值的新型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疗法至关重要。大多数显示出针对这些疾病的有用生物学特性的化合物具有杂环或多环骨架，例如泼尼松、贝壳杉烷衍生物、neblinine、芬德勒定、lycoflexine、scopaldulcicacid、月桂烯酮或刚毛精胺。不幸的是，这些产品的天然含量通常较低，需要破坏生态系统才能为患者提供治疗。因此，开发新的合成方法来快速获得这些结构极为重要。在此背景下，本提案中提出的研究计划致力于开发符合 umpolung 概念并涉及环境友好型高价碘试剂的新方法。在第一部分中，我们建议开发由烯醇醚介导的前所未有的氧化碳碳形成，一种有效地去对称化前手性二烯酮系统的不对称催化过程或一种用于快速获得精细结构的氧化多环化方法。这些方法都符合“绿色化学”的理念。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目标的合成，其化学结构可以用我们的方法快速重现。该研究计划提供的结果应通过发现应用于生物活性产品直接合成的不同新颖方法来促进知识进步。生成的大多数结构都可以用于药物开发测试。此外，通过该计划接受培训的学生可能会为具有健康益处潜力和加拿大中长期工业影响的突破性研究做出贡献。