New Tools for Absolute Molecular Structure Assignment

绝对分子结构分配的新工具

• 批准号: 1764380
• 负责人: Scott Rychnovsky
• 金额: $ 47.84万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1764380&HistoricalAwards=false
• 关键词: New; Tools; Absolute; Molecular; Structure

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.

Rychnovsky实验室得到化学部化学合成计划的支持，开发了一种新的策略来分配分子的绝对构型。 分子可能以两种可能的镜像形式存在，通常被描述为右手和左手分子。新的策略包括通过将其与两种镜像试剂反应来测试所讨论的分子，这两种镜像试剂是专门选择来区分右手和左手分子的。 确定更具反应性的试剂导致鉴定所讨论的分子的手性（构型）。两个镜像分子与蛋白质、碳水化合物和其他生物分子的相互作用不同，其中一个镜像分子通常比另一个具有更有利的性质。 大多数现代药物仅由单个镜像分子组成，因为通常两种形式中只有一种对人类健康有益。 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。本科生和研究生为本项目开展研究。 加州大学欧文分校是一个西班牙裔服务机构，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师合作，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行业和医疗部门的学生培训/就业来造福社会。该奖项支持开发用于分配分子构型的竞争性对映选择性转化（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新的试剂，用于区分具有相邻立体中心的烯烃和二烯烃。 用于指定仲醇构型的方法正在被调整以识别更广泛的结构。 该研究非常适合新的本科科学家的培训，并招募不同背景的学生参加这个项目。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培养研究技能和经验的途径。这个奖项反映了NSF的法定使命，并被认为是值得支持的，通过评估使用基金会的智力价值和更广泛的影响审查标准。

项目成果

Catalytic Enantioselective Allylations of Acetylenic Aldehydes via 2-Propanol-Mediated Reductive Coupling.

• DOI: 10.1021/acs.orglett.8b01776
• 发表时间: 2018-07-06
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Brito GA;Della-Felice F;Luo G;Burns AS;Pilli RA;Rychnovsky SD;Krische MJ
• 通讯作者: Krische MJ

Relative and Absolute Structure Assignments of Alkenes Using Crystalline Osmate Derivatives for X-ray Analysis

• DOI: 10.1021/acs.orglett.9b04133
• 发表时间: 2019-12-20
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Burns, Alexander S.;Dooley, Charles, III;Rychnovsky, Scott D.
• 通讯作者: Rychnovsky, Scott D.