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Palladium(II)‐Mediated C−H Tritiation of Complex Pharmaceuticals
Author(s) -
Yang Haifeng,
Dormer Peter G.,
Rivera Nelo R.,
Hoover Andrew J.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201711364
Subject(s) - tritium , palladium , chemistry , dipeptide , combinatorial chemistry , substrate (aquarium) , molecule , catalysis , inert , organic chemistry , peptide , biochemistry , physics , oceanography , nuclear physics , geology
Tritium‐labeled molecules are critical tools for elucidating the binding and metabolic properties of bioactive compounds, particularly during pharmaceutical discovery. Direct tritiation of inert C−H bonds with T 2 gas is an ideal approach for tritium labeling, but significant gaps remain for direct tritiation of structurally complex molecules with diverse functional groups. Here we report the first application of palladium(II) C−H activation chemistry for tritiation with T 2 gas. This practical transformation exhibits novel substrate scope and greater functional group tolerance compared to previous state of the art tritiation methods, and has been applied to directly tritiate 9 complex pharmaceuticals and an unprotected dipeptide. The isolated tritium‐labeled products exhibit >15 Ci mmol −1 specific activity, exceeding the typical requirements for application in studies of molecular interaction and metabolism.