C-N bonds synthesis towards biologically active molecules

生物活性分子的 C-N 键合成

• 批准号: 396292-2010
• 负责人: Lebel, Hélène
• 金额: $ 3.42万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Collaborative Research and Development Grants
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=487465
• 关键词: bonds; synthesis; towards; biologically; active

The global scientific objective of this project is to develop new tools for the elaboration of chiral nitrogen-containing molecules. Such types of molecules are ubiquitous components of biologically active molecules and thus of primary importance for the pharmaceutical industry. Our specific goal is to develop more efficient stereoselective synthetic strategies to streamline the synthesis of chiral nitrogen-containing molecules as single enantiomers. Numerous methods to produce C-N bonds have been reported previously. However improvements of the existing technologies as well as developments of novel approaches are still highly desirable, in particular for the synthesis of chiral amines, due to their importance as pharmacologic building blocks. The current most efficient methods for the synthesis of chiral amines are based on functional group transformations. An alternative, original and modern approach is to functionalize carbon frameworks, using metal nitrenes capable of performing C H insertions with alkanes and aziridination reactions with alkenes. Such a strategy will be highly desirable in particular if it can be performed with good stereoselectivities to produce chiral building blocks with high level of stereochemical induction. More importantly, the application of these technologies to the synthesis of molecules possessing useful pharmacological properties is instrumental to establish the scope of these methods. Giving the importance of nitrogen-containing molecules in pharmaceutical sciences, innovation in the stereoselective synthesis of these products will be greatly beneficial for a health care devoted company, such as Janssen-Ortho Inc, a member of the Johnson & Johnson worldwide family of companies. The success of such a company is directly related to its capability of producing organic molecules with high efficiency. If successful, this proposal will provide Janssen-Ortho Inc. not only novel methods to synthesize chiral nitrogen compounds, but also novel synthetic ways to streamline the elaboration of complex biologically active molecules.

该项目的全球科学目标是开发新的工具来细化手性含氮分子。这类分子是生物活性分子的普遍成分，因此对制药工业具有重要意义。我们的具体目标是开发更有效的立体选择性合成策略，以简化手性含氮分子作为单个对映体的合成。以前已经报道了许多产生碳氮键的方法。然而，现有技术的改进以及新方法的发展仍然是非常可取的，特别是对于手性胺的合成，因为它们作为药理学基础的重要性。目前最有效的手性胺合成方法是基于官能团转化。另一种新颖而现代的方法是利用能够与烷烃进行碳氢插入和与烯烃进行叠氮化反应的金属亚硝基烯功能化碳框架。这种策略将是非常可取的，特别是如果它能够以良好的立体选择性来生产具有高水平立体化学诱导的手性构建块。更重要的是，将这些技术应用于合成具有有用药理学性质的分子，有助于建立这些方法的范围。考虑到含氮分子在制药科学中的重要性，这些产品的立体选择合成的创新将极大地有利于医疗保健公司，如强生全球公司家族成员杨森ortho公司。这样一家公司的成功与它高效生产有机分子的能力直接相关。如果成功，这一提议将为Janssen-Ortho公司提供不仅新的方法来合成手性氮化合物，而且新的合成方法来简化复杂的生物活性分子的阐述。