Utility and Application of Unsaturated Acylammonium Salts in Organic Synthesis

不饱和酰铵盐在有机合成中的用途及应用

• 批准号: 1800411
• 负责人: Daniel Romo
• 金额: $ 47.96万
• 依托单位: Baylor University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800411&HistoricalAwards=false
• 关键词: Utility; Application; Unsaturated; Acylammonium; Salts

With this award, funded by the Chemical Synthesis Program of the Chemistry Division, Prof. Daniel Romo of Baylor University is developing "cascade" reactions that occur sequentially and rapidly build up structural complexity in organic molecules. As co-PI, Professor Dean Tanillo of the University of California, Davis, is studying the mechanistic details that provide for selectivity in the reactions developed in the Romo lab. Modern day organic synthesis research seeks to develop reaction processes that generate multiple carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds in a single operation, and with control of the 3-dimensionnal arrangement of atoms around carbon. This approach significantly increases the efficiency of the synthesis of a variety of molecules, including bioactive natural products and compounds of pharmaceutical interest, and provides access to molecular architectures not previously accessible. In this project, Dr. Romo is utilizing small organic molecules that serve as catalysts to activate substrates leading to initiation of various types of bond constructions with high selectivity. He is exploring a new activation mode that is already proving broadly useful for the development of novel cascade reactions, and greatly impacting efficiency in organic synthesis. Undergraduates working in the research group and in particular those associated with the "Baylor Undergraduate MiniPharma Program" that he initiated, are gaining teamwork and leadership experience, a taste of various aspects of chemical research relevant to the pharmaceutical industry, new research skills, and experience with state-of-the-art equipment, ultimately contributing to publishable research.Prof. Romo is pursuing a novel and broad design principle for organic synthesis based on readily generated chiral unsaturated acylammonium salts, significantly impacting the growing field of scalable, asymmetric organocatalysis. The organocascade processes he is studying include tandem reactions typically initiated by Michael additions (with carbon, nitrogen, and sulfur nucleophiles) that lead to highly practical, enantioselective synthetic routes to carbocycles and heterocycles commonly found in bioactive natural products and pharmaceuticals. Given the importance for organocascade catalysis, mechanistic studies of the various unsaturated acylammonium salt intermediates accessed in this research will be undertaken in collaboration with Prof. Tantillo. These collaborative studies are providing a greater understanding of the mode of activation and enantioselectivity observed with these chiral intermediates. The utility of the developed synthetic methods is being demonstrated by targeting natural products bearing beta-lactones. These in turn serve as proteomics probes with appropriate reporter tags for fundamental studies at the chemistry/biology interface with Prof. Stephan Sieber (Tech Univ of Munich, Germany). The Baylor Undergraduate MiniPharma Program enables undergraduates to get a 'taste' of the pharmaceutical industry by designing, synthesizing, and testing novel derivatives toward a common goal of identifying lead compounds for potential cancer treatment, including glioblastoma.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.

贝勒大学的丹尼尔·罗莫（Daniel Romo）教授在化学司的化学合成计划中资助了这一奖项，正在开发“级联”反应，这些反应依次，迅速地构成有机分子的结构复杂性。作为Co-Pi，加利福尼亚大学戴维斯分校的Dean Tanillo教授正在研究Romo Lab在Romo Lab中发展的反应中提供选择性的机械细节。现代有机合成研究旨在开发一种反应过程，从而在单个操作中产生多个碳碳，碳氧和碳氮键，并控制碳原子周围原子的3二维布置。这种方法显着提高了多种分子的合成效率，包括生物活性天然产物和药物的化合物，并提供了对以前无法访问的分子体系结构的访问。在这个项目中，Romo博士利用小的有机分子作为催化剂来激活底物，从而启动具有高选择性的各种类型的键结构。他正在探索一种新的激活模式，该模式已经证明对新型级联反应的发展广泛有用，并极大地影响了有机合成的效率。在研究小组中工作的本科生，尤其是与他发起的“贝勒本科生微型婚姻计划”相关的人，正在获得团队合作和领导经验，这是化学研究的各个方面的品味，与制药行业，新的研究技能以及与先进的设备相关的经验，最终为出版研究提供了贡献。罗莫（Romo）基于容易产生的手性不饱和酰基盐盐的新颖而广泛的设计原理，以实现有机合成，从而显着影响可伸缩的，不对称的有机刻分析的生长领域。他正在研究的OrganoScade过程包括通常由Michael添加（碳，氮和硫接亲核者）引发的串联反应，从而导致高度实用的，对映选择性的合成途径，可与生物活性天然产物和药物中通常发现的碳循环和杂环。鉴于有组织催化的重要性，将与Tantillo教授合作进行对本研究中各种不饱和酰胺盐中间体的机械研究。这些协作研究提供了对这些手性中间体观察到的激活和对映选择性方式的更多了解。通过靶向带有β-内酯的天然产品，正在证明开发的合成方法的效用。这些反过来用作蛋白质组学探针，并带有适当的记者标签，可与斯蒂芬·西伯（Stephan Sieber）教授（德国慕尼黑的科技大学）在化学/生物学界面进行基础研究。贝勒本科生微观计划使本科生通过设计，合成和测试新型衍生品来获得制药行业的“品尝”，以确定潜在癌症治疗的共同目标，包括胶质母细胞瘤（包括胶质母细胞瘤），包括NSF的法定任务，反映了通过评估官员的范围，这表明了依据的范围。

项目成果

Synthesis of agelastatin A and derivatives premised on a hidden symmetry element leading to analogs displaying anticancer activity

• DOI: 10.1016/j.tet.2021.132340
• 发表时间: 2021-08-17
• 期刊: TETRAHEDRON
• 影响因子: 2.1
• 作者: Xue，Haoran;Svatek，Haleigh;Romo，Daniel
• 通讯作者: Romo，Daniel

Enantioselective, Organocatalytic Strategy for the Oxazolomycin Core: Formal Synthesis of (+)-Neooxazolomycin

• DOI: 10.1021/acs.orglett.0c03511
• 发表时间: 2020-12-04
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Chaheine, Christian M.;Gladen, Paul T.;Romo, Daniel
• 通讯作者: Romo, Daniel

Simplified immunosuppressive and neuroprotective agents based on gracilin A

• DOI: 10.1038/s41557-019-0230-0
• 发表时间: 2019-04-01
• 期刊: NATURE CHEMISTRY
• 影响因子: 21.8
• 作者: Abbasov, Mikail E.;Alvarino, Rebeca;Romo, Daniel
• 通讯作者: Romo, Daniel