High-yield synthesis of a [3H]ethylenediamine ditetrodotoxin derivative

✍ Scribed by José Bontemps; Robert Cantineau; Christian Grandfils; Pierre Leprince; Guy Dandrifosse; Ernest Schoffeniels

• Publisher: Elsevier Science
• Year: 1984
• Tongue: English
• Weight: 696 KB
• Volume: 139
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1016/0003-2697(84)90400-7

✦ Synopsis

[3H]Tetrodotoxin [( 3H]TTX) and a [3H]ethylenediamine derivative of TTX are the most widely used ligands for the study of the Na channel. The former ligand presents a low specific radioactivity (1 Ci/mmol) while the latter is highly labeled (30 Ci/mmol). However, its two-step synthesis, i.e., mild oxidation followed by coupling of [3H]ethylenediamine, has been described with a low overall yield of 1.7%. In this work, more favorable experimental conditions are defined for the limiting reaction, i.e., the oxidation step, using [14C]testosterone as a model molecule. Applied to the oxidation of tetrodotoxin, this procedure produces yield values of 30-50%, as determined by high-performance liquid chromatography. Moreover, two oxidized TTX molecules appear to be covalently linked to [3H]ethylenediamine, yielding a new labeled tetrodotoxin derivative with a specific radioactivity of 45 Ci/mmol and a dissociation constant of 0.6 nM for electroplax membranes.