Novel synthetic methods and their application in total synthesis

合成具有药用价值的新生物活性化合物对治疗癌症、心血管疾病和其他医院感染是一个持续的挑战。大多数显示对这些疾病有用的生物学特性的化合物具有杂环骨架，如panacene， juglomycin a, lycoramine, mesembrine，黄曲霉毒素B或异羟基脓毒素。不幸的是，这些产品的天然含量很低，需要破坏生态系统才能治愈一些病人。因此，为了潜在的生物医学应用，发现新的合成方法来快速获得这些结构是非常重要的。在此背景下，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，我们建议根据“绿色化学”的概念开发一种无金属芳香族偶联反应，一种芳香族化合物与烯烃/炔之间的形式环加成反应和一种扩展到芳香族化合物的氧化烯丙化反应。这些转化的目的是得到可以快速用于天然产物全合成的杂环骨架。在第二部分中，我们计划实现枚举化合物的合成，其化学结构可以用我们的方法快速复制。本研究项目提供的结果将有助于通过发现不同的新方法来直接合成高生物活性产品，从而促进知识的进步。

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.