Synthesis of asymmetric [Se-75]selenoethers via carbodiimides

A convenient radiosynthesis of asymmetric [Se-75]selenoethers was developed using 1,3-disubstituted [Se-75]selenoureas as intermediates. These were pr epared from appropriate carbodiimides and hydrogen [Se-75]selenide, which c ould only be generated from carrier-added (c.a.) [Se-75]selenite in aqueous solution using phosphinic acid as reducing agent. Optimization of this ini tial labelling step with dicyclohexylcarbodiimide and polymeric N-cyclohexy lcarbodiimide-N ' -methyl polystyrene resulted in radiochemical yields (RCY ) of 73 and 55% (bound on the polymer), respectively, within 45 min. Treatm ent of [Se-75]selenoureas with alkylbromides led to corresponding [Se-75]se lenouronium salts in nearly quantitative yields. Hydrolysis under basic con ditions provided the [Se-75]selenolates and a second alkylation yielded asy mmetric [Se-75]selenoethers. Thus, within 90 min benzylmethyl[Se-75]selenid e, benzylbutyl[Se-75]selenide, benzylisopropyl[Se-75]selenide and 1-phenyl- 1-(methyl[Se-75]seleno)ethane were synthesized with respective RCY of about 59, 55, 10 and 60%. Furthermore, the Se-75-labelled alkylating agent 3-(me thyl [Se-75]seleno)-1-propanyl p-toluene-sulfonate and [Se-75]selenomethion ine were obtained with radiochemical yields of 51 and 41%, respectively. Co pyright (C) 2001 John Wiley & Sons, Ltd.