Total synthesis of alkaloid natural products and development of new synthetic tools

点击翻译按钮获取中文摘要

The discovery of new strategies for the synthesis of complex natural products represents a continuing challenge and is crucial for finding new important applications in medicine and materials science. Most of the compounds demonstrating biological properties possess a heterocyclic or a polycyclic skeleton such as alkaloids and related natural products. Unfortunately, the natural amount of these products is generally low and would require damaging an ecosystem to provide treatments. This fundamental research program aims to discover new synthetic tools to produce the main core of these structures quickly, their analogs and ultimately the targeted natural products. In this context, the research program presented in this proposal will be divided into two different and complementary parts dedicated to the elaboration of novel environmentally-friendly methodologies enabling the rapid formation of heterocyclic or cyclic motifs as well as applications of similar processes recently developed by the laboratory for the total synthesis of natural products. This proposal highlights new tools for the rapid and environmentally conscious synthesis of polyfunctionalized scaffolds involving mild, user-friendly conditions to produce the main core of natural products. New synthetic tools in heterocyclic chemistry to produce pyridine, 2-pyridone, furan and pyrroles are presented as well as an oxidative variant of the Conia-ene transformation. In addition, we propose the stereoselective total synthesis of seven alkaloids or related products such as deoxyaspidodispermine, valiolamine/voglibose, homolycorine, huperzimine, cepharatine, (dihydro)-lycoricidine and hispidospermidin. Some of these syntheses are based on a functional protecting group or a functional chiral auxiliary, which are not only a functionality moderator or a chirality inductor but also final moieties of the target. Students involved in total synthesis projects will receive a good formation; they will be trained in the concepts and methods of modern synthetic organic chemistry. Personnel with expertise in this field are very much in demand in the public and in private sectors, especially in the pharmaceutical industry.