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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612219
• 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）是手性的并且不能叠加在它们的镜像上。然而，这些化合物是最具挑战性的选择性合成，由于它们的各种化学结构之间的固有相似性。通常，当在实验室中产生手性分子时，其合成产生含有等量的两种对映异构体形式的混合物，但是虽然一种形式可能对健康有益，但另一种可能有害。另一方面，小的杂芳环在新型合成蛋白质配体的开发中具有核心重要性，这些配体最终将演变成新型药物。据估计，这些分子中有3,000多个仍然是未知的！有机合成中可用的大量成功方法已经达到了令人印象深刻的数量，但是使用具有最小环境影响的高效方法合成任何分子仍然有很长的路要走。 我们研究的具体目标将是针对发展新的和有效的方法，用于选择性（区域，化学，对映体和/或非对映体选择性）合成主要含有碳，氢，氧和氮的有机化合物。作为有机化学家，我们不仅要努力改进现有的合成方法，还要开发新的更有效的方法。为了达到这个效果，仍然需要更强大，更环保，无保护基团的。有机化学的这一领域是首要的重要性，由于今天的需要对映体纯化合物在各种相关学科（制药，农用化学品，生物学，材料科学，生物化学，食品科学等）。 为了实现这一目标，我们将开发新的工具（试剂和催化剂），以帮助控制特定化学转化的特异性。其中，环丙烷的合成和功能化，新型杂环的合成和功能化，高化学选择性的转换使用酰胺，以及催化酰胺合成是最重要的主题。我们也将集中我们的努力，了解新开发的转换的基本机制的影响。这将使我们能够建立在观察的基础上，并将化学推向更高的极限。最后，将继续进行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。催化作为绿色化学的12个基本原理之一，是绿色化学过程的关键策略之一，在新方法的开发中将发挥核心作用。 总的来说，我们的研究成果对学术和工业部门都非常重要，因为手性，非外消旋化合物是关键的中间体，将导致制药科学，农业化学科学，生物学，生物化学，食品科学，材料科学，药理学和医学等领域的新产品的开发。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将自然加强和补充他们现有的研发计划，从而帮助他们在全球经济中磨练竞争优势。此外，新一代高素质的科学家拥有独特的技能和现代思维方式的有机化学和绿色做法将得到完美的培训，加入劳动力队伍，并确保独特的专业知识流入市场。此外，从我们的研究中产生的发现的潜力将打开创新的大门，这最终将为加拿大人口创造一个更健康和更清洁的环境。