Fast Radio-Labeling and Isotope Exchange​
Proposal Acronym: FASTLabEx​​​

The impact of synthetic organic molecules on health, life quality and lifestyle is beyond doubt. It is therefore of fundamental importance to detect and quantify the fate of organic compounds and provide a precise risk/benefit assessment, before they reach the market and large public exposure. The traceless incorporation of carbon-14 allows tracking organic molecules and provides vital knowledge on their fate. This information is critical for pharmaceutical development, crop science and human food safety evaluation. Surprisingly, carbon radiolabeling still represents a bottleneck and an unsolved fundamental problem. In fact, current synthetic strategies are marred by several major drawbacks, including the generation of radioactive waste, being multi-step time-consuming and high resource-demanding. To circumvent such disadvantages, I present FASTLabEx, a novel approach for the straightforward preparation of carbon-labeled complex organic molecules that introduces the radioactive tag at the ultimate-stage of the synthesis. Inspired by efficient metal-catalyzed transformations, FASTLabEx makes use of a novel paradigm of “carbon isotope exchange", defined as the selective replacement of molecular moieties into organic molecules, by reversible molecular deconstruction/reconstruction in presence of an appropriate radiolabeled moiety. FASTLabEx will explore this concept onto a large variety of functional groups and structural diversity, far beyond the case of carboxylic acids. This approach has the potential to streamline the radio-synthesis of pharmaceuticals and agrochemicals. Outcomes from FASTLabEx will have a tangible societal impact not only for the radiochemical community, but also for pharmaceutical and agrochemical industries and in fine the consumers and patients. In order to mitigate the risks inherent to the project, preliminary results demonstrate its feasibility.

Scientific outcome from FASTLabEx: 

J. Am. Chem. Soc. 2021, 143, 5659–5665; ACS Catal. 2021, 11, 2968−2976; JACS Au, 2022, 2, 1234–1251; SynLett 2022, 33, 171-176; Eur. J. Org. Chem. 2022, ejoc.202200133; Chem. Commun. 2022, 58, 12831–12834; Angew. Chem. Int. Ed. 2023, e20​2303535; Asian J. Org. Chem. 2023, 12, e202200640; J. Am.  Chem. Soc. 2023, DOI: 10.1021/jacs.3c04679; Nat. Commun. 2023, DOI: 10.1038/s41467-023-40136-w