ORGANOFLUORINE COMPOUNDS OF BIOLOGICAL INTEREST VIA SELECTIVE FLUORINATIONS

通过选择性氟化制备具有生物意义的有机氟化合物

• 批准号: 3756094
• 负责人: MELVIN L DRUELINGER
• 金额: --
• 依托单位: COLORADO STATE UNIVERSITY-PUEBLO
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3756094
• 关键词: alcohols; amines; carbohydrates; chemical structure function; chemical synthesis; fluorine; gas chromatography; heterocyclic compounds; high performance liquid chromatography; infrared spectrometry; lipids; mass spectrometry; nuclear magnetic resonance spectroscopy; nucleosides; organic chemicals; organometallic compounds; positron emission tomography; radionuclides; thin layer chromatography; thiols; ultraviolet spectrometry; water; xenon

This project will explore synthetic routes to the generation of biologically active C-fluorinated compounds via selective fluorinations. The incorporation of fluorine into an organic system often has a pronounced effect on the biological activity of the substrate. Primary focus will be on the use of xenon difluoride as the selective fluorination reagent, although other electrophilic reagents may also be used. Key classes of compounds to be studied include carbohydrates, N- heterocycles, nucleosides, and lipids. Specific aims include the generation of new materials in quantities sufficient for biological testing and/or the development of better routes to compounds of known activity. These routes could be used with F-18 reactants to generate compounds of value involving radioisotopes for applications such as positron emission tomography. To facilitate these directed syntheses, efforts will be made to better understand the mechanism of the selective fluorinations and in particular to learn the effects of catalysts on the regioselectivity of the process. In addition to simple fluorination of pi bonds, the co-addition of other species such as alcohols, amines, water and thiols will be investigated leading to fluoroalkoxylation, etc. Routes to aromatic fluorinations via organometallics will be investigated since fluorination of the aromatic ring often greatly enhances bioactivity and direct routes to accomplish this are limited. The methods used are those standard to synthetic and mechanistic organic chemistry. A variety of chromatographic techniques (GC, HPLC, and TLC) will be used for the analysis, separation and isolation of compounds. Structural characterization will be accomplished through several spectroscopic techniques (NMR, MS, FT-lR, UV). The biological testing of the resulting compounds will be carried out by arrangement with specialists in the area of medicinal chemistry.

该项目将探索合成路线， 通过选择性氟化的生物活性C-氟化化合物。 将氟掺入有机体系中通常具有 对底物的生物活性有显著影响。初级 重点将放在使用二氟化氙作为选择性 亲电试剂，但也可以使用其它亲电试剂。 采用要研究的关键化合物类别包括碳水化合物，N- 杂环、核苷和脂质。 具体目标包括大量生产新材料 足以进行生物试验和/或开发更好的途径 已知活性的化合物。这些路线可以用于F-18 反应物，以产生涉及放射性同位素的有价值的化合物， 例如正电子发射断层扫描。为了促进这些 定向合成，将努力更好地了解 选择性氟化的机制，特别是学习 催化剂对工艺区域选择性的影响。此外 到简单的π键的加成，其他物种的共同加成， 作为醇、胺、水和硫醇将被研究， 氟烷氧基化等。 有机金属化合物将被研究，因为芳香族化合物 环通常大大提高生物活性和直接途径， 这是有限的。 所用的方法是那些标准的合成和机械有机 化学.多种色谱技术（GC、HPLC和TLC） 将用于化合物的分析、分离和离析。 结构表征将通过几个 光谱技术（NMR、MS、FT-IR、UV）。的生物学试验 所得化合物将通过与以下物质的排列进行： 药物化学领域的专家。