手性非天然氨基酸是许多上市药物和天然产物的重要合成砌块，引入手性非天然氨基酸能有效改善手性药物和天然产物的成药性。金属螯合物不对称合成手性非天然氨基酸是构建手性非天然氨基酸化合物库的重要方法，具有收率高、立体选择性强、反应条件温和、应用范围广、配体可回收、适用工业化生产等诸多优点，丰富了手性非天然氨基酸的合成种类。本项目中，我们拟开展如下研究：引入非天然手性氨基酸对先导化合物精准定点结构修饰，提高抗糖尿病和抗病毒创新药物的发现效率；将金属螯合物的合成方法应用于抗病毒和抗糖尿病药物的不对称合成，缩短合成步骤，提高合成效率，降低生产成本，优化合成工艺，为上市药物提供新的合成方法；设计合成新型金属螯合物提高非天然氨基酸化合物库的构建率；不对称合成非天然杂环氨基酸、β-氨基酸、含氟氨基酸及其衍生物，构建非天然手性氨基酸化合物库；将金属螯合物应用于非天然氨基酸的化学动力学拆分及构型反转。

Currently, chiral non-natural tailor-made amino acids are key structural units in the development of new generation of peptide-based pharmaceuticals of high impact on healthcare industry. Introducing the chiral tailor-made amino acids as synthetic blocks into a drug candidate structure usually leads to markedly improved physicochemical properties and enhanced pharmacokinetics. The known methodology for asymmetric synthesis of tailor-made amino acids, both stoichiometric and catalytic, while efficient for academic research, is prohibitively expensive and not suitable for large-scale applications. Considering the high pharmaceutical potential of tail-made amino acids and urgent need in these compounds on large scale, it is an overwhelming consensus among the scientists that the synthetic paradigm of amino acids preparation should be critically reevaluated. Such essential features as operational convenience, cost-structure and scalability, coupled with complete stereochemical outcome, are vitally important for modern, advanced synthetic methodology. In response to this changing paradigm, quite recently, the application of metal complexes have emerged as a novel and effective strategy for asymmetric synthesis of chiral tailor-made amino acids. Synthesis of chiral tailor-made amino acids via metal complexes usually features high yield, high enantioselectivity, low cost, and simple operations, easy and complete recovery of the chiral ligands, and a remarkable substrate generality. Based on these truly advantageous characteristics, we therefore are in position to fully dedicate our groups to the development of novel, advanced and efficient methods for asymmetric synthesis chiral tailor-made amino acids, including but not limited to: aliphatic, aromatic, heterocyclic and cyclic α-amino acids, β-amino acids and their derivatives via new metal complexes under readily scalable operationally convenient conditions. Our final goal will be the application of these new methods for asymmetric synthesis of important antiviral and anti-diabetic drugs. These methods are expected to provide truly practical access to various substrates of high pharmaceutical significance.