Direct 19F- and 18F- fluorination of heterocycles for medicinal chemistry and radiotracer synthesis

氟是地球上第13种最丰富的元素，主要存在于地壳的矿物成分中。生命系统并不常用这种元素，但由于C-F键的强度，这种元素在有机化学中有很多用途，有机氟化合物--含有C-F键的化合物--通常用作制冷剂、电绝缘剂和烹饪用具(如聚四氟乙烯)。有机氟化合物的另一个主要作用是在药物中，将单个氟原子放置在药物上的正确位置可以对分子的生物性质产生重大和期望的影响。在所有商业化药物中，约20%含有氟，包括各种类别的重要药物。此外，一种不稳定的氟同位素F-18经常用于正电子发射断层扫描(PET)成像，这是一项允许临床医生检查活体受试者中癌细胞生长等生化过程的技术。然而，尽管氟在制药和医学中具有重要意义，但将氟原子放置在分子的特定位置仍然是困难的。SFU的布里顿小组与世界上最大的制药公司之一F.Hoffmann LaRoche合作，开发了几种方法，在温和的条件下将氟原子引入分子中。这使得新的氟化分子的产生成为可能，包括F-18标记分子，可以通过PET成像检测小鼠体内的癌症肿瘤。这一研究项目旨在扩大生物医学研究人员可用的方法，以快速、温和地将氟原子引入药物分子中，以优化其性质，或用于创建新的PET显像剂。

Fluorine is the 13th most abundant element on earth, and exists primarily in mineral compositions in the earths crust. It is not commonly used by living systems, but this element has found many uses in organic chemistry, due to the strength of the C-F bond, and organofluorine compounds - compounds that contain a C-F bond - are commonly used as refrigerants, electric insulants and cookware (as PTFE). Another major role for organofluorine compounds is in drugs, where placing a single fluorine atom in the correct position on a pharmaceutical can have major and desireable impact on the biological properties of the molecule. Of all commercialized drugs, approximately 20% contain fluorine, including important drugs in various classes. Furthermore, an unstable isotope of fluorine, F-18, is routinely used for positron emission tomography (PET) imaging, a technique that allows clinicians to examine biochemical processes such as cancer cell growth in a live subject. However, despite the importance of fluorine in pharmaceuticals and medicine, it is still difficult to place a fluorine atom in a specific position of a molecule. The Britton group at SFU, in collaboration with F. Hoffmann LaRoche - one of the largest pharmaceutical companies in the world - has developed several methods to introduce a fluorine atom into a molecule under gentle conditions. This has enabled the creation of novel fluorinated molecules, including F-18 labeled molecules that can detect cancerous tumors in mice via PET imaging. This research project aims to expand the methods available to biomedical researchers to quickly and gently introduce a fluorine atom into drug molecules for the purpose of optimizing their properties, or for the purposes of creating new PET imaging agents.