DESIGNING LIGANDS USING COMPUTATIONAL TECHNIQUES

非对映选择性和对映选择性化学反应已成为高效合成复杂手性目标物的关键，包括天然产物、新材料、生物探针和药物。虽然传统的方法对不对称的过程依赖于直观或随机筛选的方法，使用计算技术来开发新的和改进的方法还有待开发。我们的总体目标是开发一系列合理的设计协议，用于识别新的手性助剂和催化剂的重要合成反应，通过良好描绘的过渡态进行。特别是，我们正在使用的过程中，确定诺埃尔配体家族通过计算筛选的数据纳入大型结构数据库，如剑桥结构数据库。作为该计划的一部分，我们打算证明，高水平的从头计算过渡态能量可以定期相关的溶液相反应性，这样的结果将提供一个宝贵的工具，在反应发展。该计划的成功可能会极大地改变手性配体的设计方式;即使在组合环境中，也可以选择在优化后成功概率很高的新型核心支架。

Diastereo- and enantioselective chemical reactions have become essential for the efficient synthesis of complex chiral targets, including natural products, novel materials, biological probes, and pharmaceuticals. While the conventional approach toward asymmetric processes has relied upon intuitive or random screening approaches, the use of computational techniques to develop novel and improved methods has yet to be exploited. Our overall aim is to develop a series of rational design protocols for the identification of new chiral auxiliaries and catalysts for important synthetic reactions, that proceed through well delineated transition-states. In particular, we are using a process that identified noel ligand families via computational screening of data incorporated within large structural databases such as Cambridge Structural Database. As part of this program, we intend to demonstrate that high level ab initio calculations of transition state energies can be correlated to solution phase reactivity on a regular basis; such a result would provide an invaluable tool in reaction development. The success of this program could dramatically change the way chiral ligands are designed; even in a combinatorial setting, where novel core scaffolds could be selected that had a high probability of success upon optimization.