Synthesis of the AChE inhibitor [phenyl-7-3H] (−)-phenserine tartrate at high specific activity

Tritium-labelled alkaloids: Synthesis and applications

“…Although exact synthetic preparation details appear to be lacking in the literature, [ 3 H]physostigmine has been used in numerous biological studies including photoaffinity labelling of the nicotinic acetylcholine receptor . We have also tritiated the physostigmine phenyl analogue phenserine ( 2 ) using a halogenation‐catalytic tritium dehalogenation approach, demonstrating the position of tritium installation by both tritium and proton nuclear magnetic resonance (NMR) . The indole glucosinolate glucobrassicin, prevalent in most cruciferous plants, was also radiolabelled by means of a bromination‐catalytic tritium dehalogenation procedure to study its metabolism …”

GABAergic radioligands labelled with tritium

“…Because GABA cannot itself cross the blood brain barrier (BBB), one proposed way to raise therapeutically useful levels of its concentration would be to interfere with this enzyme. Suicide enzyme substrates have often been used for this purpose, and we have been very interested in the tritiation of these agents 137, 138. Regarding GABA, one of the most potent and selective of GABA transaminase inhibitors was found to be 4‐amino‐5‐hexenoic acid ( 33 ), initially discovered by Merrell International chemists in France 139, 140.…”

Direct metal‐catalyzed tritiation of organic compounds

“…We have tritium labelled a number of substances with Crabtree's catalyst, but for confidentiality reasons we can only disclose a few examples at this time. Roflumilast ( 12 ) is an anti‐inflammatory drug that acts as an enzyme inhibitor for the phospho‐diesterase enzyme PDE‐4 and we have long been interested in the tritiation of such suicide enzyme substrates 22, 23. To the best of our knowledge the tritiation of 12 has not yet been reported and its structure presented limited options for high specific activity radiolabelling.…”