Tritium hydrogen ‐isotope exchange with electron‐poor tertiary benzenesulfonamide moiety; application in late‐stage labeling of T0901317

Described is a late-stage tritium labeling of T0901317 using an HIE strategy in the electron-poor substrate lacking a goodortho-directing group for C ─H activation. Homogeneous catalysis with a Kerr-type catalyst provided [3H]T0901317 with SA of 10.8 Ci/mmol. Unprecedented translation issue of deuterium into tritium experiment during heterogeneous catalysis was observed, whereby efficient deuterium labeling conditions using Ir-black provided reasonable 0.72 D-enrichment of T0901317 but turned out to be ineffective when repeated under similar conditions in tritium experiments. The multifunctional radioligand [3H]T0901317 ([3H]1) has been employed as a powerful autoradiographic tool to target several receptors, such as liver X, farnesoid X, and retinoic acid-related orphan receptor alpha and gamma subtypes at nanomolar concentrations. Although [3H]1 is commercially available and its synthesis via tritiodebromination has been reported, the market price of this radioligand and the laborious synthesis of corresponding bromo-intermediate potentially preclude its widespread use in biochemical, pharmacological, and pathological studies in research lab settings. We exploit recent reports on hydrogen-isotope exchange (HIE) reactions in tertiary benzenesulfonamides where the sulfonamide represents anortho-directing group that facilitates CH activation in the presence of homogenous iridium(I) catalysts. Herein, we report a time- and cost-efficient method for the tritium late-stage l...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research