METAL MEDIATED SCHIFF BASES FOR MEDICINAL AGENT SYNTHESIS

用于药物合成的金属介导席夫碱

• 批准号: 6347540
• 负责人: XIU R BU
• 金额: $ 6.95万
• 依托单位: CLARK ATLANTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6347540
• 关键词: Schiff bases; acetaldehyde; biological products; catalyst; chemical binding; chromium; drug design /synthesis /production; gas chromatography; manganese; metal complex; stereoisomer; titanium

Our research is aimed to develop low-cost and highly efficient asymmetric catalysts for practical uses in pharmaceutical syntheses, e.g. synthesis of intermediates that are of biological importance for natural products and/or ethical drug components. Chiral medicines have been recognized as the medicines of the future of high clinical relevancy, low toxicity and cost-effectiveness of low dosage as well as minimization of environment impact. This research is to address important issues towards the chemistry development in chiral medicines. Our approach includes rational design, synthesis and characterization of chiral ligands as well as the development of chiral complexes from the ligands by incorporation of metal ions with. The organ transformation of inexpensive pro-chiral substrates into requisite chiral compounds will be achieved using the developed chiral complexes as catalysts. The project is a logic extension of our development of chiral Schiff bases catalysts for reactions important to the construction of bioactive medicinal agents. Special motifs induced into chiral ligands are important for complexes to exhibit high enantioselectivity, high reactivity and stability. New chiral catalysts proposed in this project will take advantage of discovered disciplines to use the most effective steric effect groups and their positions capable of differentiating space for high enantioselectivity. The catalysts are designed to have Salen ligands that possess "wall type" bulky groups to provide steric hindrance which is to be optimized with the position. Through this research, a clear correlation between microstructure and enantioselectivity will be established and efficient catalysts for practical application will be anticipated.

我们的研究旨在开发低成本、高效率的不对称催化剂，用于药物合成，例如合成对天然产物和/或伦理药物成分具有重要生物学意义的中间体。手性药物被认为是临床相关性强、毒性低、低剂量、低成本、对环境影响最小的未来药物。这项研究是为了解决手性药物化学发展的重要问题。我们的方法包括手性配体的合理设计、合成和表征，以及通过将金属离子与手性配体结合来开发手性配合物。利用开发的手性络合物作为催化剂，将实现廉价的亲手性底物向必需的手性化合物的器官转化。该项目是我们开发手性席夫碱催化剂的逻辑延伸，用于对构建生物活性药物非常重要的反应。在手性配体中引入特殊的基序是使配合物具有高对映体选择性、高反应活性和稳定性的重要因素。本项目中提出的新型手性催化剂将利用已发现的规律，利用最有效的空间效应基团及其位置来区分空间，以获得高的对映选择性。催化剂被设计成具有Salen配体，这些配体具有“壁型”大基团，以提供空间位阻，该位阻将随着位置的变化而优化。通过本研究，将建立微观结构与对映体选择性之间的明确关联，并有望得到具有实际应用价值的高效催化剂。