Reactivos de yodo hipervalente: especies clave para la 18F-radiofluoración rápida de esqueletos areno bioactivos


San José Gracia, Marc  


The present work is framed within the scope of methodological chemistry applied to the preparation of fluorine-18 radiotracers used in the context of Positron Emission Tomography (PET). The relevance of the subject is marked by the key role that the technique (PET) has acquired as an imaging tool in biomedical research, both in the clinical and preclinical fields. However, this preponderance contrasts with the inherent difficulty in the isotopic labeling of certain bioactive aromatic skeletons, structures that are also very present in the field of medical chemistry. In this context, it is where hypervalent iodine species gain relevance due to their excellent ability to participate as leaving groups easily displaced by 18F generated in a cyclotron.
The review work that has been carried out is aimed at the development and synthesis of a suitable hypervalent iodine precursor based on the chloroquine skeleton, a molecule that has proven to be key within the area of ​​gene therapy applied to the treatment of degenerative diseases. retinal cells associated with aging.
In this context, the first part of this work reviews the key processes for the formation of diaryl iodoni salts, an area that received an important boost in the last decade from groups specialized in the PET technique. Among other aspects, the synthesis of this type of λ3-iodans is proposed both for transmetalation and for electrophilic aromatic substitution methods (SEAr). However, advanced methods and structures are approaching, including one-pot processes and those that allow access to highly functionalized skeletons, such as heterocyclic structures, one of which (chloroquine) is precisely the one on the horizon. The second part consists of a critical review of the most relevant methods and mechanisms of [18F] -radiofluorination of hypervalent iodine precursors. Among other aspects, it is proposed starting with the classical pathways to the most advanced applications that allow access to [18F] -radiotraçadors of structures of biomedical interest, including neurotransmitters. In view of the challenge that diaryl iodoni salts can present at the level of radiofluoro regioselectivity, this section also addresses the important advance based on the use of iodoni iodine species, which have been shown to be capable of giving rise to processes highly selective.



Cuenca González, Ana Belén 


IQS SE - Undergraduate Program in Chemistry