Computer-aided design of chiral ligands. Part 2. Functionality mapping as a method to identify stereocontrol elements for asymmetric reactions.
Computer-aided design of chiral ligands. Part 2. Functionality mapping as a method to identify stereocontrol elements for asymmetric reactions.
复制标题
手性配体的计算机辅助设计。
DOI：
10.1021/jo020401s
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Panda,Manoranjan
中科院分区：
文献类型：
--
作者：
Kozlowski,MarisaC;Panda,Manoranjan
提出了一种基于力场能量最小化的计算方法来确定官能团相对于立体选择反应过渡态的能量有利位置。概述了这种功能映射的参数、目标过渡态的特征以及探头结构的特征。我们的方法被发现重现了一些已知手性配体的立体识别片段的位置，这些手性配体包括Masamune二甲基硼烷、二甲基硼烷、Corey Stien试剂、Roush烯丙基硼酸盐酒石酸酯和MacMillan描述的仲胺Diels−Alder催化剂。通过提供不同配体组分通过非键相互作用提供的稳定/失稳的定量测量，功能映射可以更好地理解导致产物的过渡态中的特定相互作用。该方法可以确定手性配体是否通过稳定一条反应途径、通过破坏反应途径的稳定或通过两者的组合来提供观察到的选择性。关于潜在官能团的取向和位置信息很容易获得。除了作为一种分析工具外，官能图还可以用来探索设计新的手性配体的起点。
A computational method to determine the energetically favorable positions of functional groups with respect to the transition states of stereoselective reactions based on force field energy minimization is presented. The parameters of this functionality mapping, the characteristics of the target transition states, and the features of the probe structures are outlined. Our method was found to reproduce the positions of the stereodiscriminating fragments for some known chiral ligands including the Masamune dimethylborolane, dimenthylborane, the Corey stien reagent, the Roush allylboronate tartrates, and the secondary amine Diels−Alder catalysts described by MacMillan. Functionality mapping can be used to better understand the specific interactions in the transition states leading to the products by providing a quantitative measure of the stabilization/destabilization afforded by the different ligand components via nonbonded interactions. The method can determine if a chiral ligand imparts the observed selectivity by stabilizing one reaction pathway, by destabilizing a reaction pathway, or by a combination of both. Orientational as well as positional information about potential functional groups is readily obtained. In addition to its utility as an analytical tool, functionality mapping can be used to explore starting points for the design of new chiral ligands.