Synthesis and Structure Analysis of Natural Products

天然产物的合成与结构分析

• 批准号: 2101674
• 负责人: Scott Rychnovsky
• 金额: $ 48.5万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2101674&HistoricalAwards=false
• 关键词: Synthesis; Structure; Analysis; Natural; Products

With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Scott Rychnovsky of the University of California, Irvine is developing new strategies to assign the structure and handedness of molecules. Molecules may exist in two possible mirror-image forms, which are commonly described as right-handed or left-handed structures. New molecules are isolated from plants and animals, and are created in the lab by chemists. The structure of molecules determine their physical properties such as their physical form, liquid or solid, and how they interact with living systems. Odor and taste come from the shape and structure of a molecule. More significantly, molecular drugs are effective because their shapes interact with proteins to alleviate diseases. The Rychnovsky group is using osmium complexes to simplify the determination of structure of new molecules, as well as computer modeling. In difficult cases, the final step to proving a structure consists of constructing the molecule in a lab from simpler components—chemical synthesis. Undergraduate and graduate students will carry out the research for this project. UC Irvine is a Hispanic Serving Institution, providing 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 to help their students develop their research skills and expertise. This project is expected to have a strong impact on student training, helping to build the future STEM (science, technology, engineering and mathematics) workforce for both careers in industry and in academia.The award supports the development of osmate derivatives to improve the crystallinity of complex molecules. Osmates are often highly crystalline, and the density of the osmium metal facilitates the determination of structure and handedness by X-ray crystallography (anomalous dispersion). Chemical synthesis tools are also being developed, including a new intramolecular Diels-Alder reaction that builds new six-membered rings with easily predicted geometries. Computational modeling of spectroscopic properties is used to test plausible structure to determine if they correctly match the newly isolated molecular structures. Comparing the computer-predicted properties with the measured properties is a powerful technique to determine molecular structure. A final test is to build the best proposed structure from simpler fragments to prove that it matches the newly isolated molecule. The research is well suited for the training of undergraduate and graduate 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.

在化学系化学合成（SYN）项目的支持下，欧文市加州大学的Scott Rychnovsky教授正在开发新的策略来分配分子的结构和手性。分子可能以两种可能的镜像形式存在，通常被描述为右手或左手结构。新分子是从植物和动物中分离出来的，由化学家在实验室中创造出来。分子的结构决定了它们的物理性质，例如它们的物理形式，液体或固体，以及它们如何与生命系统相互作用。气味和味道来自分子的形状和结构。 更重要的是，分子药物是有效的，因为它们的形状与蛋白质相互作用，以减轻疾病。Rychnovsky小组正在使用锇络合物来简化新分子结构的确定以及计算机建模。在困难的情况下，证明一个结构的最后一步是在实验室里用更简单的成分--化学合成--构建分子。本科生和研究生将为本项目进行研究。加州大学欧文分校是一个西班牙裔服务机构，提供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，帮助学生发展他们的研究技能和专业知识。该项目预计将对学生培训产生重大影响，有助于为工业界和学术界的职业生涯建立未来的STEM（科学、技术、工程和数学）人才队伍。该奖项支持锇酸盐衍生物的开发，以提高复杂分子的结晶度。锇酸盐通常是高度结晶的，锇金属的密度有利于通过X射线晶体学（异常色散）确定结构和手性。 化学合成工具也在开发中，包括一种新的分子内Diels-Alder反应，该反应可以构建具有易于预测几何形状的新六元环。光谱性质的计算建模用于测试合理的结构，以确定它们是否正确地匹配新分离的分子结构。将计算机预测的性质与测量的性质进行比较是确定分子结构的一种强有力的技术。最后一个测试是从更简单的片段中构建最佳的结构，以证明它与新分离的分子相匹配。该研究非常适合本科生和研究生科学家的培训，并招募了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

Total Syntheses of Strasseriolide A and B, Antimalarial Macrolide Natural Products

Strasseriolide A和B的全合成，抗疟药大环内酯天然产物

• DOI: 10.1021/acs.orglett.1c04340
• 发表时间: 2022
• 期刊: Organic Letters
• 影响因子: 5.2
• 作者: Salituro, Leah J.;Pazienza, Jessica E.;Rychnovsky, Scott D.
• 通讯作者: Rychnovsky, Scott D.