New Tools for Absolute Molecular Structure Assignment

通过该奖项，由化学系的化学合成计划资助，来自加州大学欧文分校的Scott Rychnovsky教授和他的研究小组正在开发一种简单的方法来分配分子的绝对构型。 复杂分子可能以两种可能的镜像形式存在，这两种镜像分子与蛋白质、碳水化合物和其他生物分子相互作用产生不同的结果。 大多数现代药剂仅由具有最佳特性的单个镜像分子组成，类似地，天然产物被分离为两种可能的镜像之一。 将分子转化为正确的镜像结构（构型）是开发新药物、研究新的天然产物分子以及了解它们与细胞、动物、人类和其他生物相互作用的重要一步。该奖项支持开发用于分配分子构型的竞争对映选择性转化（CEC）策略。通过测量对两种对映体（镜像）催化剂或试剂的反应速率来评估新分子。 动力学拆分催化剂是理想的，因为它们以高的对映选择性反应，在匹配的情况和错配的情况之间显示出显着的速率差异。通过测量对映体纯分子相对于试剂的两种对映体的速率或转化率，可以鉴定快速反应试剂。 与已知的例子进行比较，可以确定分子的绝对构型。 该计划的重点是开发一种高灵敏度的醇类方法，一种高通量的醇类方法，以及一种改进的胺类方法。 一个新的反应被用来确定环氧乙烷的构型。正在开发的用于胺、环氧乙烷和醇的补充方法将使绝对构型的确定成为有机化学中的一个简单过程。

Through this award, funded by the Chemical Synthesis Program of the Division of Chemistry, Prof. Scott Rychnovsky and his research group from the University of California, Irvine, are developing a straightforward method to assign the absolute configuration of molecules. Complex molecules may exist in two possible mirror-image forms, and the two mirror-image molecules interact with proteins, carbohydrates and other biological molecules to produce different results. Most modern pharmaceutical agents are composed of only a single mirror image molecule with the best properties, and similarly natural products are isolated as one of two possible mirror images. Assigning molecules to the correct mirror image structure (configuration) is an important step in the developing new pharmaceutical agents, studying new natural product molecules, and in understanding their interactions with cells, animals, humans and other living creatures.The award supports development of the Competing Enantioselective Conversion (CEC) strategy for assigning the configuration of molecules. The new molecule is evaluated by measuring rates of reaction against two enantiomeric (mirror image) catalysts or reagents. Kinetic resolution catalysts are ideal because they react with high enantioselectivity, showing significant rate differences between a matched case and a mismatched case. By measuring the rate or conversion of an enantiopure molecule against the two enantiomers of the reagent, the fast-reacting reagent can be identified. Comparison with known examples allows the absolute configuration of the molecule to be assigned. The program focuses on developing a highly sensitive method for alcohols, a high-throughput method for alcohols, and an improved method for amines. A new reaction is being investigated to assign the configuration of oxiranes. The complementary methods that are being developed for amines, oxiranes and alcohols will make the determination of absolute configuration a straightforward process in organic chemistry.