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

CATALYST项目支持历史悠久的黑人学院和大学(HBCU)致力于建立教职员工的研究能力，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职员工的研究能力，改善学院的研究和教学，并让本科生参与研究经验。这一奖项授予林肯大学(MO)，支持教师和本科生在开发环-双(硅基)肼方面的研究经验，这是一种新型的肼试剂。具体地说，该提议寻求创造第一个强的无金属碱的Wolff-Kishner类型的GEM-在中性条件下对羰基碳(C=O)进行二氟化反应，从而合成出生物活性分子。该建议的总体目标是开发一种新的无金属基后期宝石二氟化技术，将醛和酮的羰基碳(C=O)转化为CF2基团，从而产生一类新的联氨试剂。本项目分为五个具体目标：(1)开发新的环-双(硅基)肼试剂的合成和提纯方案；(2)研究新的环-双(硅基)肼试剂在不同有机溶剂中的互变异构化平衡并评价其水解性；(3)发展一种利用环-双(硅基)肼试剂合成肼类化合物的通用方法；(4)利用环-双(硅基)肼类化合物建立醛和酮的羰基碳的宝石二氟化反应新方法。以及(5)通过对具有生物活性的复杂分子--海参皂苷元醋酸酯进行宝石二氟化来验证所提出的氟化技术的实用性。将利用基本的合成化学原理和技术来合成新型试剂。这些化合物将使用闪蒸柱层析进行纯化，并通过1H、19F、13C-核磁共振和HRMS技术进行表征。反应的进展将通过薄层色谱(TLC)和1H，19F核磁共振进行监测。拟议研究的成功完成将为酮和醛的羰基碳(C=O)的后期宝石二氟化提供新的环-双(硅基)肼试剂，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智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.