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（HBCU）提供了支持，以努力建立教师的研究能力，以增强科学，技术，工程和数学（STEM）本科教育和研究。可以预期，该奖项将进一步进一步促进教职员工的研究能力，改善机构的研究和教学，并让本科生参与研究经验。该奖项颁发给林肯大学（MO），支持了循环双（Silyl）hydrazines的教师和本科研究经验，这是一种新颖的夹心试剂类。具体而言，该提案旨在在中性条件下创建第一个强大的金属碱基基 - 基什纳型宝石 - 脱氟化（C = O），从而导致合成生物活性分子。该提案的总体目标是开发新的金属碱基无后期宝石二氟化技术，用于将醛和酮的羰基碳（C = O）转化为CF2组，从而导致新的夹层夹层试剂。该项目已分为五个具体目的：（1）为拟议的环状双（Silyl）氢津试剂制定合成和纯化方案，（2）研究新环状 - 双基（Silyl）氢氮一种试剂的综合溶液的综合溶液和一般液压液的综合方法（3）合成（3）的合成方法（3），研究了新环状 - 双基（SILYL）氢氮术的折线平衡（3） （4）使用环状双（Silyl）氢援酮来开发醛和酮的羰基碳碳碳的新的宝石 - 二氟化方法，（5）通过执行提出的compote soct soct socter hhsecote hhsecote hhsecote hhsecote，基本的合成化学原理和技术将用于合成新型试剂。这些化合物将使用Flash柱色谱法纯化，并以1H，19F，13C-NMR和HRMS技术为特征。反应的进展将通过薄层色谱法（TLC）和1H，19F NMR监测。拟议的研究的成功完成将提供新的环状氢津试剂（SILEL）氢氮试剂，用于酮和醛的碳碳碳（C = O）的晚期宝石二氟化，而无需使用任何强大的金属基础。该奖项反映了NSF的法定任务，反映了通过评估构成的构成商品的支持。