Diphenylhydantoin, labelled

Preparation of a Tracer for Diphenylhydantoin Labeled with a (Cyclopentadienyl)dicarbonyl Iron (Fp) Entity... 

It has been proposed that metabolic activation of diphenylhydantoin may be responsible for the teratogenicity. After the administration of radioactively labeled diphenylhydantoin to pregnant mice, radioactive drug or a metabolite was found to be covalently bound to protein in the embryo. It was shown that both the teratogenicity and embryolethality of diphenylhydantoin could be increased by using an inhibitor of epoxide hydrolase (see chap. 4), trichloropropene oxide. Similarly, the covalent binding of radiolabeled diphenylhydantoin to protein was also increased by this treatment. 

VAn Langenhove, A., Costello, C. E., Biller, J. E., Biemann, K., and-Browne, T. R. (1982). A gas chromatographic/mass spectrometric method for the simultaneous quantitation of 5,5-diphenylhydantoin, its p-hydroxylated metabolite and their stable isotope labeled analogs. Clin. Chim. Acta 115, 263-275. 

In the case of amphetamine, the coupling is carried out directly from its primary amine [48]. Labeling of diphenylhydantoin was carried out by coupling onto 3-(2-aminoethyl)-5,5-diphenylhydantoin 36 [49], the latter amino derivative having been prepared by the method of O Neal [50]. In the case of phenobarbital, labeling is effected by coupling between m-aminophenobarbital 38 and cobaltocenium carboxylic acid hexafluorophosphate 39 in the presence of DCC [51]. Preparation of m-aminophenobarbital 38 was by electrochemical reduction of the nitro derivative 14 [51], whose synthesis is outlined in Scheme 8.9. 

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