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Development of modern late-stage fluorination reactions with [18F]

[18F]现代后期氟化反应的发展

基本信息

批准号：
9020238
负责人：
Tobias Ritter
金额：
$ 42.26万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-20 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9020238
关键词：
Address Alcohols Applications Grants Area Chemicals Chemistry Clinical Clinical Research Communities Complex Data Development Diagnosis Diagnostic Disease Disease Progression Fluorides Fluorine Functional disorder Goals Grant Health Hospitals Human Image Imaging technology Isotopes Label Learning Malignant Neoplasms Mediating Methods Modification Monitor Motivation One-Step dentin bonding system Patient Care Pharmaceutical Chemistry Pharmacologic Substance Phenols Physiology Plant Roots Positron Positron-Emission Tomography Radiochemistry Reaction Reagent Research Route Site Staging Technology Tracer analog base clinical care design drug development human disease hydroxyl group improved molecular imaging nervous system disorder non-invasive imaging nonhuman primate novel pre-clinical prognostic programs radiotracer small molecule tool treatment response

项目摘要

In this grant application, we propose to develop and optimize two new fluorine-18 (18F) reactions for the synthesis of 18F-labeled small molecules as useful, generally available tools for positron emission tomography (PET). Our goal is to provide readily available reagents that can be used by the entire radiochemistry community for the robust and simple synthesis of 18F-fluorinated probes from readily available materials. Our preliminary data suggest that the proposed reactions combine the simplicity of conventional fluorination chemistry with the large substrate scope of modern late-stage fluorination reactions. Our approach is enabled by novel chemical reactivity that can convert available materials directly into the corresponding fluorinated analogs. Positron emission tomography (PET) is a non-invasive, high sensitivity imaging technology that can be used to diagnose and study human diseases. PET can provide information about normal or aberrant human physiology and is a powerful tool for monitoring disease progression and treatment response. Over the past decade, PET imaging has had an impact in studying several diseases, such as cancer and neurological diseases, and is also beginning to expedite the development of new pharmaceuticals. However, the vast majority of molecules (even those that contain fluorine) cannot currently be labeled with the positron-emitting 18F isotope necessary for imaging. A clear need exists for more versatile and robust radiochemistry methods for incorporation of the 18F isotope. Our lab has invented a new reagent and a new reaction to incorporate the positron-emitting nuclide 18F into molecules based on new chemical reactivity. We have already demonstrated that we can provide aryl and alkyl fluorides from readily available phenols and alcohols, respectively. We propose here reaction development to furnish practical, readily performed methods for the synthesis of PET probes. Reaction optimization will be guided by a mechanism-based approach. We will showcase the utility and generality of our new methods by preparing eight radiotracers that are challenging to prepare with conventional methods.

在这项拨款申请中，我们建议开发和优化两个新的氟-18(18F)反应，用于 18F标记小分子的合成作为常用的正电子发射工具断层扫描(PET)。我们的目标是提供现成的试剂，供所有人使用放射化学界为强健和简单地从易得合成18F-氟化探针可用的材料。我们的初步数据表明，所提出的反应结合了现代后期氟化大底物范围的常规氟化化学反应。我们的方法是通过新的化学反应来实现的，这种化学反应可以将可用的材料直接转化为相应的氟化类似物。正电子发射断层扫描(PET)是一种无创、高灵敏度的成像技术，可以用于诊断和研究人类疾病。宠物可以提供有关正常或异常的信息它具有人体生理功能，是监测疾病进展和治疗反应的有力工具。在过去的十年里，PET成像在几种疾病的研究中产生了影响，例如癌症和此外，还在加快新药的开发。然而，绝大多数分子(即使是那些含有氟的分子)目前还不能被标记具有成像所需的发射正电子的18F同位素。显然存在着对更多用途和更多用于18F同位素掺入的可靠的放射化学方法。我们实验室发明了一种新的试剂和一种新的反应来掺入发射正电子的核素18F 根据新的化学反应转化为分子。我们已经证明，我们可以提供分别从易得的酚和醇中得到芳基和烷基氟化物。我们在这里求婚反应发展，为合成PET探针提供实用、易于执行的方法。反应优化将以基于机理的方法为指导。我们将展示该实用程序和通过制备8种具有挑战性的放射性示踪剂来概括我们的新方法传统的方法。

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Late-stage deoxyfluorination of alcohols with PhenoFluor.

DOI：
10.1021/ja3125405
发表时间：
2013-02-20
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Sladojevich, Filippo;Arlow, Sophie I.;Tang, Pingping;Ritter, Tobias
通讯作者：
Ritter, Tobias

PhenoFluor: Practical Synthesis, New Formulation, and Deoxyfluorination of Heteroaromatics.

DOI：
10.1021/op500121w
发表时间：
2014-08-15
期刊：
Organic process research & development
影响因子：
3.4
作者：
Fujimoto T;Becker F;Ritter T
通讯作者：
Ritter T

Alkyl Aryl Ether Bond Formation with PhenoFluor.

DOI：
10.1002/anie.201500902
发表时间：
2015-05-04
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
影响因子：
16.6
作者：
Shen, Xiao;Neumann, Constanze N.;Kleinlein, Claudia;Goldberg, Nathaniel W.;Ritter, Tobias
通讯作者：
Ritter, Tobias

Palladium(III)-catalyzed fluorination of arylboronic acid derivatives.