Catalyst Project: New Hydrazine Reagents for Late-Stage Diversification of Bioactive Molecules

催化剂项目：用于生物活性分子后期多样化的新型肼试剂

• 批准号: 2200600
• 负责人: Manish Singh
• 金额: $ 15万
• 依托单位: Lincoln University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2200600&HistoricalAwards=false
• 关键词: Catalyst; Project; New; Hydrazine; Reagents

Catalyst Projects provide support for Historically Black Colleges and Universities (HBCU) to work towards establishing research capacity of faculty to strengthen science, technology, engineering, and mathematics (STEM) undergraduate education and research. It is expected that the award will further the faculty member's research capability, improve research and teaching at the institution, and involve undergraduate students in research experiences. This award to Lincoln University (MO) supports faculty and undergraduate research experiences in the development of cyclic-bis(silyl)hydrazines, a novel class of hydrazine reagents. Specifically, the proposal seeks to create the first strong metal-base free Wolff-Kishner type gem-difluorination of carbonyl carbons (C=O) under neutral conditions, result in synthetically made bioactive molecules. The overarching goal of the proposal is to develop a new metal-base free late-stage gem-difluorination technique for converting the carbonyl carbon (C=O) of aldehydes and ketones into CF2 group, resulting in a new class of hydrazine reagents. This project has been divided into five specific aims: (1) to develop synthetic and purification protocols for the proposed cyclic-bis(silyl)hydrazine reagents, (2) to study the tautomeric equilibrium of the new cyclic-bis(silyl)hydrazine reagents in different organic solvents and assess their hydrolytic stability, (3) to develop a general method for synthesis of hydrazones using cyclic-bis(silyl)hydrazine reagents, (4) use the cyclic-bis(silyl)hydrazones to develop a new gem-difluorination methodology of carbonyl carbon of aldehydes and ketones, and (5) validate the utility of the proposed fluorination technique by performing the gem-difluorination of a bioactive complex molecule, hecogenin acetate. Basic synthetic chemistry principles and techniques will be used to synthesize the novel reagents. These compounds will be purified using flash column chromatography and characterized by 1H, 19F, 13C-NMR, and HRMS techniques. Progress of the reaction will be monitored by Thin Layer Chromatography (TLC) and 1H, 19F NMR. Successful completion of the proposed research will provide new cyclic-bis(silyl)hydrazine reagents for late-stage gem-difluorination of carbonyl carbon (C=O) of ketones and aldehydes without using any strong metal-base.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.

催化剂项目为历史上的黑人学院和大学（HBCU）提供支持，致力于建立教师的研究能力，以加强科学，技术，工程和数学（STEM）本科教育和研究。预计该奖项将进一步提高教师的研究能力，改善研究和教学机构，并参与本科生的研究经验。该奖项授予林肯大学（MO），支持教师和本科生在环状双（甲硅烷基）肼（一种新型肼试剂）开发方面的研究经验。具体而言，该提案旨在在中性条件下创建第一个强金属基自由的Wolff-Kishner型羰基碳（C=O）宝石，从而合成生物活性分子。该提案的总体目标是开发一种新的无金属基后期Gem-Differentiation技术，用于将醛和酮的羰基碳（C=O）转化为CF2基团，从而产生一类新的肼试剂。该项目分为五个具体目标：（1）发展所提出的环状双（硅基）肼试剂的合成和纯化方案，（2）研究新的环状双（硅基）肼试剂在不同有机溶剂中的互变异构平衡并评估它们的水解稳定性，（3）发展使用环状双（硅基）肼试剂合成腙的通用方法，（4）利用环状双（硅基）腙建立了一种新的醛和酮羰基碳的偕-双链反应方法;（5）通过对生物活性复合物hecogenin acetate进行偕-双链反应来验证所提出的双链反应技术的实用性。基本的合成化学原理和技术将用于合成新的试剂。将使用快速柱色谱法纯化这些化合物，并通过1H、19 F、13 C-NMR和HRMS技术进行表征。将通过薄层色谱法（TLC）和1H、19 F NMR监测反应进程。成功完成拟议的研究将提供新的环状双（甲硅烷基）肼试剂，用于酮和醛的羰基碳（C=O）的后期偕-二聚反应，而无需使用任何强金属碱。该奖项反映了NSF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。