New Methods for the Stereoselective Synthesis of Organic Compounds

有机化合物立体选择性合成的新方法

• 批准号: RGPIN-2014-06438
• 负责人: Charette, André
• 金额: $ 12.02万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=632814
• 关键词: New; Methods; Stereoselective; Synthesis; Organic

Most important molecules found in nature (enzymes, proteins, RNA, DNA, etc.) are chiral and cannot be superimposed upon their mirror image. Yet, these compounds are the most challenging to selectively synthesize due to their inherent similarity between various chemical structures. Normally, when a chiral molecule is produced in the laboratory, its synthesis produces a mixture containing equal amounts of two enantiomer forms, but while one form may be beneficial to health, the other may be harmful. On the other hand, small heteroaromatic rings are of central importance in the development of novel synthetic protein ligands that will eventually evolve into novel drugs. It is estimated that over 3,000 of these molecules are still unknown! The plethora of successful methodologies available in organic synthesis has reached an impressive number, but there is still a long way to go to synthesize any molecule using highly efficient methods having minimal environmental impact. The specific aim of our research will be directed towards the development of new and efficient methods for the selective (regio-, chemo-, enantio- and/or diasteroselective) synthesis of organic compounds containing mostly carbon, hydrogen, oxygen and nitrogen. As organic chemists, we always strive not only to improve existing synthetic methods, but also to develop new and more effective ones. To that effect, more powerful, greener, and protecting-group-free are still needed. This area of organic chemistry is of primary importance due to today’s necessity for enantiomerically pure compounds in a variety of related disciplines (pharmaceuticals, agrochemicals, biology, material sciences, biochemistry, food sciences, etc.). In order to achieve this, we will develop novel tools (reagents and catalysts) to help control the specificity of a given chemical transformation. Among the priorities, cyclopropane synthesis and functionalization, novel heterocycle synthesis and functionalization, highly chemoselective transformations using amides, as well as catalytic amide synthesis are the most important themes. We will also concentrate our efforts on understanding the fundamental mechanistic implications of the newly developed transformations. This will allow us to build upon observations and push the chemistry to higher limits. Finally, the synthesis of complex natural products will be pursued, since this is the ultimate ground to test the efficiency of new synthetic methodologies. Catalysis, which is featured as one of the 12 principles of Green chemistry and as one of the key strategies to use in Green chemical processes, will play a central role in the development of new methods.Overall, the fruits of our research will be extremely important for both the academic and industrial sectors, because chiral, non-racemic compounds are critical intermediates that will lead to the development of new products in fields as diverse as pharmaceutical science, agrochemical science, biology, biochemistry, food science, materials sciences, pharmacology and medicine. Considering that several chemistry-related companies are based in the greater Montreal area, we anticipate that our research will naturally strengthen and complement their existing R&D programs, thus help them hone their competitive edge in the global economy. As well, a new generation of highly qualified scientists possessing unique skills and a modern mindset on organic chemistry and green practices will be perfectly trained to join the workforce and to ensure a flow of unique expertise into the marketplace. In addition, the potential for discoveries that will emerge from our research will open the door to innovation, which, ultimately, will create a healthier and cleaner environment for the Canadian population at large.

自然界中发现的最重要的分子（酶、蛋白质、RNA、DNA 等）都是手性的，不能叠加在它们的镜像上，然而，由于这些化合物的各种化学结构之间固有的相似性，选择性合成最具挑战性。通常，当在实验室中生产手性分子时，其合成会产生含有等量的两种对映异构体形式的混合物，但虽然一种形式可能有益于健康，但另一种形式可能有害，另一方面，小的杂芳环则有害。至关重要据估计，其中 3,000 多种分子仍是未知的。有机合成中可用的成功方法已达到令人印象深刻的数量，但仍有很长的路要走。我们研究的具体目标是开发新的、有效的选择性（区域选择性、化学选择性、对映选择性和/或非对映选择性）方法。作为有机化学家，我们不仅致力于改进现有的合成方法，而且致力于开发新的、更有效的、更强大、更环保的合成方法。由于当今各种相关学科（制药、农用化学品、生物学、材料科学、生物化学、食品科学、为了实现这一目标，我们将开发新的工具（试剂和催化剂）来帮助控制给定化学转化的特异性，其中包括环丙烷合成和功能化、新型杂环合成和功能化、使用高度化学选择性转化。酰胺以及催化酰胺合成是最重要的主题，我们还将集中精力了解新开发的转化的基本机制含义，这将使我们能够在观察的基础上推动化学发展。最后，将追求复杂天然产物的合成，因为这是测试新合成方法效率的最终基础，催化是绿色化学的12条原则之一，也是关键之一。在绿色化学过程中使用的策略，将在新方法的开发中发挥核心作用。总的来说，我们的研究成果对于学术和工业部门都极其重要，因为手性、非外消旋化合物是关键的中间体，将带动新产品的开发考虑到几家化学相关公司都位于大蒙特利尔地区，我们预计我们的研究自然会加强和补充它们。现有的研发计划，从而帮助他们磨练在全球经济中的竞争优势。此外，拥有独特技能和有机化学和绿色实践现代思维的新一代高素质科学家将接受完美培训，加入劳动力队伍并确保他们的发展。独特的专业知识流入此外，我们研究中的潜在发现将为创新打开大门，最终将为加拿大广大人民创造一个更健康、更清洁的环境。