Organometallic Chemistry for Applications in Biomedical Sciences

有机金属化学在生物医学科学中的应用

• 批准号: 8401547
• 负责人: Tobias Ritter
• 金额: $ 31.26万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-20 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8401547
• 关键词: Acids; Address; Alzheimer' s Disease; Applications Grants; Area; Carbon; Chemicals; Complex; Dopa; Fluorides; Fluorine; Goals; Ligands; Mediating; Mental Depression; Methods; Molecular; Organometallic Chemistry; Parkinson Disease; Pharmacologic Substance; Positron-Emission Tomography; Property; Reaction; Reagent; Research; Schizophrenia; Science; Silanes; Source; Staging; Tracer; Transition Elements; base; drug development; functional group; man; metal complex; molecular imaging; paxil; prevent; public health relevance; silane

DESCRIPTION (provided by applicant): Carbon-fluorine bond formation is a challenging chemical transformation, especially when used for the synthesis of arylfluorides. Simple molecules can be fluorinated with fluorination methods developed during the last 100 years, molecules of greater complexity, however, cannot. The current inability of chemists to efficiently make complex organic fluorides by late-stage fluorination often prevents research in diverse areas, such as drug development and molecular PET imaging. The proposed research addresses the chemical challenges of carbon-fluorine bond formation to synthesize functionalized arylfluorides. Our strategy for carbon-fluorine bond formation is based on organometallic chemistry. We proposed Pd- and Ag- mediated fluorination reaction of arylstannanes, arylboronic acids, and arylsilanes. Additionally we propose to develop transition metal fluoride complexes that react as electrophilic fluorination reagents using anionic fluoride as ultimate fluorine source. We further propose to synthesize four biologically active molecules via late-stage fluorination using our transition-metal mediated approach. A long-term-goal of our research is the application of our fluorination reactions to the synthesis of currently unavailable PET tracers for molecular imaging using positron-emission tomography. The application of the fluorination reactions to molecular imaging is beyond the scope of this grant proposal.

描述（由申请人提供）：碳氟键的形成是一种具有挑战性的化学转化，特别是用于合成芳基氟化物时。简单分子可以用近100年来发展起来的氟化方法进行氟化，但更复杂的分子却不能。目前，化学家无法通过后期氟化有效地制造复杂的有机氟化物，这往往阻碍了药物开发和分子PET成像等不同领域的研究。提出的研究解决了碳氟键形成合成功能化芳基氟化物的化学挑战。我们的碳氟键形成策略是基于有机金属化学。我们提出了钯和银介导的芳基锡烷、芳基硼酸和芳基硅烷的氟化反应。此外，我们建议开发过渡金属氟配合物，以阴离子氟作为最终氟源，作为亲电氟化试剂反应。我们进一步提出利用过渡金属介导的方法通过后期氟化合成四种生物活性分子。我们研究的一个长期目标是将我们的氟化反应应用于合成目前不可用的PET示踪剂，用于使用正电子发射断层扫描进行分子成像。氟化反应在分子成像中的应用超出了本拨款提案的范围。