Novel synthetic methods and their application in total synthesis

新的合成方法及其在全合成中的应用

• 批准号: 341582-2008
• 负责人: Canesi, Sylvain
• 金额: $ 2.92万
• 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: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=458462
• 关键词: Novel; synthetic; methods; their; application

Synthesis of new bioactive compounds of pharmaceutical interest represents a continuing challenge for curing cancer, cardiovascular diseases and other nosocomial infections. Most of the compounds demonstrating useful biological properties against these diseases possess a heterocyclic skeleton such as panacene, juglomycin A, lycoramine, mesembrine, aflatoxin B or isohydroxypsorofebrin. Unfortunately, the natural amount of these products is low and would require damaging an ecosystem to heal some patients. Consequently, it is extremely important to discover new synthetic methods to get these structures quickly for a potential biomedical application. In this context, the research program presented in this proposal is dedicated to the development of novel methodologies in heterocyclic chemistry. In a first part, we propose to develop a metal free aromatic coupling reaction accordingly to the concept of "green chemistry", a formal cycloaddition reaction between aromatics compounds and alkenes/alkynes and an oxidative allylation reaction extended to aromatic compounds. The aim of these transformations is to get heterocyclic skeletons that could be rapidly used in the total synthesis of natural products. In a second part, we plan to achieve the synthesis of enumerated compounds, whose chemical structures could be quickly reproduced with our methodologies. Results afforded by this research program should contribute to the knowledge advancement by the discovery of different novel methodologies applied to the direct synthesis of highly bioactive products.

具有药用价值的新生物活性化合物的合成代表了治疗癌症、心血管疾病和其他医院感染的持续挑战。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骨架，例如panacene、胡桃霉素A、石蒜胺、mesembrine、黄曲霉毒素B或异羟基山梨醇酯。不幸的是，这些产品的天然量很低，需要破坏生态系统才能治愈一些患者。因此，发现新的合成方法以快速获得这些结构以用于潜在的生物医学应用是极其重要的。在这种情况下，本提案中提出的研究计划致力于开发杂环化学的新方法。在第一部分中，我们根据“绿色化学”的概念，提出了发展一种无金属的芳香族偶联反应，即芳香族化合物与烯烃/炔之间的形式环加成反应和延伸到芳香族化合物的氧化烯丙基化反应。这些转化的目的是得到可快速用于天然产物全合成的杂环骨架。在第二部分中，我们计划实现所列举的化合物的合成，其化学结构可以用我们的方法快速再现。本研究计划提供的结果应有助于通过发现应用于直接合成高生物活性产品的不同新方法来促进知识进步。