New Tools for Absolute Molecular Structure Assignment

Rychnovsky实验室由化学部门的化学合成项目提供支持，以开发一种分配分子绝对构型的新策略。分子可能以两种可能的镜像形式存在，这两种形式通常被描述为右手分子和左手分子。新的策略包括通过与两种镜像试剂反应来测试有问题的分子，这两种镜像试剂是专门选择来区分右手分子和左手分子的。确定反应性更强的试剂可以确定所讨论的分子的手性（结构）。两种镜像分子与蛋白质、碳水化合物和其他生物分子的相互作用不同，其中一种镜像分子通常比另一种具有更有利的性质。大多数现代药物仅由单一镜像分子组成，因为通常只有两种形式中的一种对人体健康有益。将分子分配到正确的镜像结构（构型）是开发新的药物制剂、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步骤。本课题由本科生和研究生进行研究。加州大学欧文分校是一所西班牙裔服务机构，它提供了充足的机会招募有才华的西班牙裔（和其他少数民族）学生参加这个项目。Rychnovsky教授与圣地亚哥社区学院的教职员工合作，为学生提供发展研究技能和专业知识的途径。该项目通过促进人类健康以及改善制药工业和医疗部门的学生培训/就业，造福社会。该奖项支持用于分配分子构型的竞争性对映选择性转化（CEC）策略的开发。新分子是通过测量反应速率对两个对映体（镜像）催化剂或试剂进行评估。动力学分辨率催化剂是理想的，因为它们具有高的对映体选择性，在匹配的情况下和不匹配的情况下表现出显著的速率差异。通过测量对映纯分子对试剂的两个对映体的速率或转化率，可以识别快速反应的试剂。与已知的例子比较，可以确定分子的绝对构型。该计划的重点是开发新的试剂来区分具有相邻立体中心的烯烃和二烯。分配仲醇构型的方法正在适应于识别更多种类的结构。该研究非常适合培养新的本科科学家，并招募了不同背景的学生参与该项目。圣地亚哥社区学院有很多转到加州大学系统的学生，但他们很少有机会参与研究项目。Rychnovsky教授与那里的教师合作，招募暑期学生参加这个研究项目，从而为社区大学的学生提供了一个发展研究技能和经验的途径。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The Rychnovsky lab is supported by the Chemical Synthesis Program in the Chemistry Division to develop a new strategy to assign the absolute configuration of molecules. Molecules may exist in two possible mirror-image forms, which are commonly described as right-handed and left-handed molecules. The new strategy involves testing the molecule in question by reacting it with two mirror-image reagents specially chosen to differentiate right-handed and left-handed molecules. Determining the more reactive reagent leads to identification of the handedness (configuration) of the molecule in question. Two mirror-image molecules interact with proteins, carbohydrates and other biological molecules differently, with one of the mirror-image molecules often having more favorable properties than the other. Most modern pharmaceutical drugs are composed of only a single mirror image molecule as often only one of the two forms are beneficial to human health. 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. Undergraduate and graduate students carry out the research for this project. UC Irvine is a Hispanic Serving Institution, which provides ample opportunities to recruit talented Hispanic (and other minority) students to participate in this project. Professor Rychnovsky works with the faculty at Santiago Community College providing their students with an avenue to develop their research skills and expertise. This project benefits society by advancing human health as well as improving student training/employment in the pharmaceutical industries and medical sector.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 allow the absolute configuration of the molecule to be assigned. The program focuses on developing new reagents for differentiating alkenes and dienes with adjacent stereogenic centers. The method for assigning secondary alcohol configuration is being adapted to identify a wider variety of structures. The research is well suited for the training of new undergraduate scientists, and students with diverse backgrounds are recruited to participate in this project. Santiago Community College has many students who transfer to the UC system, but they rarely have the opportunity to participate in research projects. Professor Rychnovsky works with the faculty there to recruit summer students to take part in this research program, thus providing an avenue for community college students to develop research skills and experience.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.