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

生物碱天然产物的全合成及新型合成工具的开发

• 批准号: RGPIN-2021-03305
• 负责人: Canesi, Sylvain
• 金额: $ 2.62万
• 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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742485
• 关键词: Total; synthesis; alkaloid; natural; products

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.

复杂天然产物合成新策略的发现是一个持续的挑战，对于在医学和材料科学中寻找新的重要应用至关重要，大多数具有生物特性的化合物都具有杂环或多环骨架，例如生物碱和相关天然物质。不幸的是，这些产品的天然含量通常较低，并且需要破坏生态系统才能提供治疗方法，该基础研究计划旨在发现新的合成工具来快速生产这些结构的主要核心、其类似物以及最终的目标天然产品。在此背景下，研究计划。该提案中提出的内容将分为两个不同且互补的部分，致力于阐述新型环保方法，能够快速形成杂环或环状基序，以及实验室最近开发的类似工艺的应用，用于天然产物的全合成。该提案强调了用于快速且环保地合成多官能化支架的新工具，涉及温和、用户友好的条件来生产天然产物的主要核心，以生产吡啶、还提出了 2-吡啶酮、呋喃和吡咯以及 Conia-ene 转化的氧化变体。此外，我们还提出了七种生物碱或相关产品的立体选择性全合成，例如脱氧阿哌啶胺、缬醇胺/伏格列波糖、高山蒜碱、石杉碱甲、头孢哌啶。 ，(二氢)-石蒜素和刚毛亚精胺是其中一些合成的基础。功能性保护基团或功能性手性助剂，它们不仅是功能调节剂或手性诱导剂，而且是目标的最终部分，他们将得到良好的概念和培训；公共和私营部门，特别是制药行业，非常需要具有该领域专业知识的人员。