METAL MEDIATED SCHIFF BASES FOR MEDICINAL AGENT SYNTHESIS

我们的研究旨在开发低成本和高效的不对称催化剂，用于药物合成的实际应用，例如合成对天然产物和/或伦理药物成分具有生物重要性的中间体。手性药物已被公认为具有高临床相关性、低毒性和低剂量成本效益以及对环境影响最小的未来药物。本研究旨在解决手性药物化学发展的重要问题。我们的方法包括合理设计、合成和表征手性配体，以及通过将金属离子掺入到配体中来开发手性配合物。利用开发的手性配合物作为催化剂，将廉价的前手性底物转化为必需的手性化合物。该项目是我们开发手性希夫碱催化剂的逻辑延伸，对生物活性药物的构建具有重要意义。手性配体中诱导的特殊基序是配合物具有高对映选择性、高反应活性和稳定性的重要因素。本项目提出的新型手性催化剂将利用已发现的学科，利用最有效的空间效应基团及其能够区分空间的位置，实现高对映体选择性。该催化剂被设计为具有“壁型”庞大基团的Salen配体，以提供空间位阻，该位阻随位置而优化。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系，并为实际应用提供有效的催化剂。

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.