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。 它通常不被生命系统使用，但由于C-F键的强度，这种元素在有机化学中有许多用途，有机氟化合物-含有C-F键的化合物-通常用作制冷剂，电绝缘体和炊具（如PTFE）。 有机氟化合物的另一个主要作用是在药物中，其中将单个氟原子放置在药物的正确位置可以对分子的生物学特性产生重大和期望的影响。 在所有商业化的药物中，大约20%含有氟，包括各种类别的重要药物。 此外，氟的不稳定同位素F-18通常用于正电子发射断层扫描（PET）成像，这是一种允许临床医生检查生物化学过程（如活体受试者中的癌细胞生长）的技术。 然而，尽管氟在制药和医学中的重要性，但仍难以将氟原子置于分子的特定位置。 SFU的布里顿小组与F.霍夫曼·拉罗什（Hoffmann LaRoche）是世界上最大的制药公司之一，已经开发出多种在温和条件下将氟原子引入分子的方法。 这使得新型氟化分子的产生成为可能，包括F-18标记的分子，这些分子可以通过PET成像检测小鼠的癌性肿瘤。 该研究项目旨在扩展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，以优化其性能或创造新的PET成像剂。

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.