基于碘鎓盐化学多样性合成轴手性联芳基化合物的反应研究及应用

How to efficiently synthesize the structurally diverse, optically active axially chiral biaryls have important research value and application prospect. In consideration of their importance and synthetic challenge, based on the cyclic diaryliodonium salt chemistry, the construction of non-bridged axially chiral biaryls will be developed firstly by using the heteroatom arylation strategy. Based on this platform, a series of axially chiral biaryls which could be used as ligands, can be prepared easily by further diversity-oriented transformations. Then various bridged axially chiral biaryls, especially the synthetically challenging medium-sized-ring skeletons will be constructed by employing the atom- and step-economical decarboxylative cross-coupling/cyclization strategy. On this basis, the reaction mechanisms will be studied intensively, and the chiral induction and transfer mechanisms will be revealed. Finally, a structurally diverse library of biaryl small molecules will be established according to the principles of drug design, and the anti-gastric cancer activities will be evaluated. This research will not only provide a new train of thought for the design and synthesis of the axially chiral biaryls, but more importantly, it will produce a batch of valuable and novel axially chiral (non)bridged (hetero)biaryls with diverse structure and wide chemical space, which potentially could be used as anti-gastric cancer lead compounds. The successful conduction of this research can provide theoretical basis for the axially chiral biaryl drug discovery.

如何高效地合成多样性的光学纯轴手性联芳基化合物具有重要的研究价值和应用前景。鉴于它们的重要性和合成挑战性，本项目拟基于二芳基环状碘鎓盐化学，首先发展利用杂原子芳基化策略构筑开链联芳基轴手性骨架的方法。以此为平台，经过进一步的衍生，可以多样性地合成一系列具有配体应用价值的轴手性联芳基化合物。接着利用具有原子和步骤经济性的脱羧偶联/环化串联反应，发展高效构筑各种轴手性联(杂)芳基桥环(特别是具有合成挑战性的中环)骨架的方法。在此基础上，将深入开展反应机理研究，揭示反应手性诱导和传递机制。最后利用药物设计原理，建立一个多样性联芳基小分子化合物库，开展抗胃癌生物活性评价。该研究不仅能够为此类分子的设计和合成提供新的思路，更重要的是开发一批结构多样、化学空间覆盖范围广的高品质新型联芳基轴手性分子，揭示其作为抗胃癌药物先导化合物方面的潜在功能，从而为轴手性联芳基药物的研发提供理论基础。

光学纯轴手性联芳基化合物的高效和合成多样性的具有重要的研究价值和应用前景。基于它们的重要性和合成挑战性，本项目立足于二芳基环状碘鎓盐化学，首先发展了利用杂原子芳基化策略构筑开链联芳基轴手性骨架的方法。以此为基础，经过进一步的衍生，多样性地合成了一系列具有配体应用价值的轴手性联芳基化合物。接着利用具有原子和步骤经济性的脱羧偶联/环化串联反应，发展高效构筑各种轴手性联(杂)芳基桥环(特别是具有合成挑战性的中环)骨架的方法。在此基础上，深入开展了反应机理研究，揭示了反应手性诱导和传递机制。该研究不仅能够为此类分子的设计和合成提供新的思路，更重要的是开发一批结构多样、化学空间覆盖范围广的高品质新型联芳基轴手性分子，揭示其作为药物先导化合物方面的潜在功能。