Final Report Summary - FLUOPET (Late Stage Fluorination for Positron Emission Tomography Applications)
Fluorine Chemistry is an extremely relevant research area that has enabled the discovery of new drugs and agrochemicals, the diagnostic imaging of diseases such as cancer and Alzheimer in humans via Positron Emission Tomography (PET) and the development of new materials. During this fellowship, important discoveries have been made, that will contribute to advance the field of fluorine chemistry, especially its applications in drug discovery and imaging.
An operationally simple protocol for the selective 19F-deoxyfluorination of structurally complex molecules has been discovered. Several fluorinated derivatives of natural products and pharmaceuticals have been prepared to showcase the potential of the method.
The work has been published in Journal of the American Chemical Society (J. Am. Chem. Soc. 2013, 135, 2470–2473) and the paper has been one of the 10 most accessed manuscripts during the period February-March.
The reagent used in the discovered method is now commercialized by major fine-chemicals companies such as Aldrich and Strem.
A new series of reagents for the perfluoroalkylation of organic molecules has been discovered. These new reagents allow the use of gaseous CF3I and CF3CF2I in a new formulation that renders them liquid and easy to handle, by making use of halogen-bonding interactions. The utility of the new reagents has been showcased in a large series of perfluoroalkylation reactions. The invention allows medicinal chemists and material chemists to prepare fluorinated compounds in a much easier way.
The work has been published in Angewandte Chemie, International Edition (ACIE, 2015, 54, 3712–3716) and a patent application has been filed.
The utility of the reagents has been highlighted in several Medicinal Chemistry Forums, such as Corante (http://pipeline.corante.com/archives/2015/03/03/put_away_the_lecture_bottle.php(opens in new window)).
A second area of impact for this fellowship has been in Positron Emission Tomography (PET). PET is a powerful non-invasive, real-time imaging technology that can be used to identify and characterize human disease, but is currently limited by deficiencies in chemistry. While simple molecules such as fluorodeoxy-glucose (FDG) can be efficiently prepared, more complex, biomedically interesting molecules often cannot. The short half-life of 18F (110 min) dictates severe restrictions on the chemical synthesis of PET tracers.
During the third year of this fellowship, the radiosynthesis of two new compounds with potential application in imaging has been developed. The compounds are currently under investigation for the in vivo imaging of Fibroblast Activation Protein (FAP) and the receptor 5-HT3. Both receptors are highly important targets of current medicinal chemistry programs and are involved in several diseases such as cancer (FAP) and neurodegenerative dieseases (5-HT3).
An operationally simple protocol for the selective 19F-deoxyfluorination of structurally complex molecules has been discovered. Several fluorinated derivatives of natural products and pharmaceuticals have been prepared to showcase the potential of the method.
The work has been published in Journal of the American Chemical Society (J. Am. Chem. Soc. 2013, 135, 2470–2473) and the paper has been one of the 10 most accessed manuscripts during the period February-March.
The reagent used in the discovered method is now commercialized by major fine-chemicals companies such as Aldrich and Strem.
A new series of reagents for the perfluoroalkylation of organic molecules has been discovered. These new reagents allow the use of gaseous CF3I and CF3CF2I in a new formulation that renders them liquid and easy to handle, by making use of halogen-bonding interactions. The utility of the new reagents has been showcased in a large series of perfluoroalkylation reactions. The invention allows medicinal chemists and material chemists to prepare fluorinated compounds in a much easier way.
The work has been published in Angewandte Chemie, International Edition (ACIE, 2015, 54, 3712–3716) and a patent application has been filed.
The utility of the reagents has been highlighted in several Medicinal Chemistry Forums, such as Corante (http://pipeline.corante.com/archives/2015/03/03/put_away_the_lecture_bottle.php(opens in new window)).
A second area of impact for this fellowship has been in Positron Emission Tomography (PET). PET is a powerful non-invasive, real-time imaging technology that can be used to identify and characterize human disease, but is currently limited by deficiencies in chemistry. While simple molecules such as fluorodeoxy-glucose (FDG) can be efficiently prepared, more complex, biomedically interesting molecules often cannot. The short half-life of 18F (110 min) dictates severe restrictions on the chemical synthesis of PET tracers.
During the third year of this fellowship, the radiosynthesis of two new compounds with potential application in imaging has been developed. The compounds are currently under investigation for the in vivo imaging of Fibroblast Activation Protein (FAP) and the receptor 5-HT3. Both receptors are highly important targets of current medicinal chemistry programs and are involved in several diseases such as cancer (FAP) and neurodegenerative dieseases (5-HT3).