Carbamoyl Fluorides: From Synthesis to Radiochemistry
Résumé
Fluorinated compounds are present in a wide range of applications, especially in life sciences such as medicinal chemistry or medical imaging. Such a growing interest has led to the development of innovative fluorinated moieties leading to obtain new specific properties and applications. Carbamoyl fluoride is still an underdeveloped functional group, mainly due to the scarcity of efficient synthetic methods and the lack of knowledge regarding its physico-chemical properties. In this study, an efficient method to easily synthesize carbamoyl fluoride, starting from the corresponding amine, was designed using the DNTFB/DMAP system . This new approach uses inexpensive and non-toxic reagents and provides the expected carbamoyl fluoride under mild conditions and with good yields . The physico-chemical properties of carbamoyl fluoride were then studied. Thus, the lipophilicity parameter as well as the stability in the pH range and the compatibility with various conditions mimicking the physiological environment were also determined. Together with the radioisotope fluorine-18, fluorinated molecules can also be used in PET imaging for various applications ranging from drug design, pharmacological studies to medical diagnosis. Such uses require efficient methods for the late stage radiolabeling of the molecules under fast and mild conditions. For this purpose, we developed an 18F/19F isotopic exchange to perform radiolabeling under mild conditions with good radiochemical yields. The labeled compounds were obtained directly, without further purification, with excellent chemical and radiochemical purity.