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Synthesis of specifically labeled (S)‐nicotine‐5‐ 3 H and (S)‐cotinine‐5‐ 3 H BY carrier free tritiolysis of the corresponding 5‐bromo derivatives
Author(s) -
Shigenaga Mark K.,
Jacob Peyton,
Trevor Anthony,
Castagnoli Neal,
Benowitz Neal
Publication year - 1987
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580240614
Subject(s) - chemistry , triethylamine , cotinine , sodium borohydride , tetrahydrofuran , reductive amination , bromine , formaldehyde , solvent , sodium tetraphenylborate , acetaldehyde , nicotine , zinc , nuclear chemistry , catalysis , organic chemistry , medicinal chemistry , ethanol , ion , neuroscience , biology
The synthesis of high specific activity tritium labeled (S)‐nicotine and (S)‐cotinine has been achieved. (S)‐5‐Bromonornicotine of high enantiomeric purity was converted to the corresponding (S)‐5‐bromonicotine by reductive amination with formaldehyde and sodium borohydride. Tritiolysis of this intermediate with carrier free tritium in the presence of triethylamine using 10% Pd/C catalyst provided (S)‐nicotine‐5‐ H with a specific activity of 32 Ci/mmol in ethanol solvent and 28 Ci/mmol in tetrahydrofuran solvent. Similarly, tritiation of (S)‐5‐bromocotinine, obtained by oxidation of (S)‐5‐bromocotinine, obtained by oxidation of (S)‐5‐bromonicotine with bromine followed by reduction of the intermediate (S)‐3′, 3′, 5‐tribromonicotine with zinc dust, yielded the corresponding (S)‐cotinine‐5‐ H (22.8 Ci/mmol). All reactions proceeded in good to excellent yields.