DESIGNING LIGANDS USING COMPUTATIONAL TECHNIQUES

非对映和对映选择性化学反应已成为有效合成复杂手性靶标的必要条件，包括天然产物、新材料、生物探针和药物。虽然非对称过程的传统方法依赖于直觉或随机筛选方法，但使用计算技术开发新颖和改进的方法尚未得到开发。我们的总体目标是开发一系列合理的设计方案，用于识别新的手性助剂和催化剂，用于重要的合成反应，这些反应通过良好描述的过渡态进行。特别是，我们正在使用一种过程，通过计算筛选纳入大型结构数据库（如剑桥结构数据库）的数据来识别新的配体家族。作为该计划的一部分，我们打算证明过渡态能量的高水平从头计算可以定期与溶液相反应性相关；这样的结果将为反应发展提供宝贵的工具。这个项目的成功可能会极大地改变手性配体的设计方式；即使在组合设置中，也可以选择具有高概率成功优化的新型核心支架。

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.