Carbon isotope exchange mediated by vanadium complexes

钒配合物介导的碳同位素交换

• 批准号: 10711850
• 负责人: Konstantin Bukhryakov
• 金额: $ 34.65万
• 依托单位: FLORIDA INTERNATIONAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711850
• 关键词: Alkenes; Area; Biology; C14 isotope; Carbon; Carbon Isotopes; Chemistry; Clinical Drug Development; Collection; Complex; Development; Drug Kinetics; Ethylenes; Isotope Labeling; Isotopes; Label; Mediating; Medicine; Metabolic; Methods; Natural Products; Pharmaceutical Preparations; Pharmacologic Substance; Positron-Emission Tomography; Procedures; Process; Protocols documentation; Source; Transition Elements; Vanadium; Work; catalyst; dehydrogenation; design; drug candidate; functional group; innovation; isotope incorporation; methyl group; methyl iodide; pre-clinical; tool

Project Summary The proposed studies focus on the design, synthesis, and development of a range of vanadium- based catalysts to perform carbon isotope exchange via =*CH2 (*C = 11C, 13C, and 14C) group transfer between terminal olefins. Carbon isotope exchange is an emerging area that allows incorporating carbon- 14 isotope directly into target compounds for metabolic and pharmacokinetic studies. Furthermore, the integration of carbon-11 into pharmaceuticals is an indispensable tool in positron emission tomography. The innovation of the proposed work is the development of olefin metathesis catalysts based on the first-row transition metal, vanadium, to take advantage highly polarized V=C bond. These V alkylidenes feature enabled regioselective formation of metallacyclobutane, resulting in reversible =CH2 transfer between terminal olefins without formation of cross-products and ethylene, which is supported by our preliminary results and DFT studies. Therefore, V-catalyze carbon isotope exchange can serve as a new platform to incorporate labeled carbon atoms into a wide range of pharmaceuticals and natural products without developing new multi-step synthetic strategies. The proposed approach uses accessible labeled iodomethane (*CH3I) as a carbon isotope source and can be applied to compounds containing various common functional groups. The method will be expanded to alkyl-containing bioactive molecules utilizing a tandem dehydrogenation/olefin metathesis strategy. Therefore, the first example of carbon isotope exchange involving the methyl group will be introduced. The utility of the new concepts, catalysts, and protocols will be emphasized through applications to the concise synthesis of isotopically labeled pharmaceuticals and natural products.

项目摘要 这些研究的重点是设计、合成和开发一系列钒- 通过=* CH 2（*C = 11 C、13 C和14 C）基团转移进行碳同位素交换的基于催化剂 在末端烯烃之间。碳同位素交换是一个新兴领域，它允许将碳- 14同位素直接转化为目标化合物用于代谢和药代动力学研究。而且 将碳-11整合到药物中是正电子发射断层摄影术中不可或缺的工具。的 本论文的创新点在于开发了基于第一排烯烃的烯烃复分解催化剂 过渡金属钒，以利用高度极化的V=C键。这些V亚烷基具有 能够区域选择性地形成金属环丁烷，导致之间可逆的= CH 2转移 末端烯烃而不形成交叉产物和乙烯，这得到了我们初步的支持。 结果和DFT研究。因此，钒催化碳同位素交换可以作为一个新的平台， 将标记的碳原子掺入到广泛的药物和天然产物中， 开发新的多步合成策略。所提出的方法使用可访问的标记 碘甲烷（* CH 3 I）作为碳同位素源，并且可以应用于含有各种 常见的功能群。该方法将被扩展到利用一个或多个分子的含烷基生物活性分子。 串联脱氢/烯烃复分解策略。因此，碳同位素的第一个例子 将引入涉及甲基的交换。新概念、催化剂和 协议将强调通过应用程序的简明合成同位素标记 药品和天然产品。