Org Biomol Chem. 2025 Nov 3. doi: 10.1039/d5ob01419k. Online ahead of print.
ABSTRACT
The pentafluorosulfanyl group (-SF5) is one of the most promising fluorinated functional groups, recently developed as an alternative to the trifluoromethyl group (-CF3) in drug design. Fluorine-18 allows researchers to investigate in vivo activity and biodistribution of novel fluorinated drugs; however, currently no methods are reported to radiolabel -SF5 moieties. In this work we report the first successful radiolabelling of such a group by isotopic exchange, and we show peculiar reaction trends. We studied this reaction using model compounds and functionalized amino acids, also adopting an unbiased approach to reaction optimization to minimize cognition bias. The results have been analyzed by standard statistical methods and Artificial Intelligence (AI) tools. Finally, we serendipitously discovered the production of two radioactive products from one precursor, that we hypothesize being positional radioisotopologues that interact differently with the chromatographic stationary phase; if further proven, this finding hints, for the first time, at a case of chemical differences between molecules containing 19F and 18F.
PMID:41178415 | DOI:10.1039/d5ob01419k
