Organometallic Chemistry for Applications in Biomedical Sciences

描述(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。简单的分子可以用过去100年发展起来的氟化方法进行氟化，而更复杂的分子则不能。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，这往往阻碍了不同领域的研究，如药物开发和分子PET成像。这项拟议的研究解决了碳氟键形成的化学挑战，以合成功能化的芳基氟化物。我们的碳氟键形成策略是基于有机金属化学的。我们提出了Pd和Ag介导的芳基锡烷、芳基硼酸和芳基硅烷的氟化反应。此外，我们还建议开发以阴离子氟化物为最终氟源的过渡金属氟化物络合物作为亲电氟化试剂。我们进一步建议使用我们的过渡金属介导法通过后期氟化来合成四个生物活性分子。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无法利用正电子发射断层扫描进行分子成像的PET示踪剂。氟化反应在分子成像中的应用超出了这项拨款提案的范围。

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.