SYNTHESIS OF H-2-LABELED, H-3-LABELED AND C-14-LABELED CP-45,634 (SORBINIL)

The syntheses of H-3- and C-14-labelled S-(+)-6-fluoro-2,3-dihydrospiro-[4H-1-benzopyran-4,4'-imidazolidin]-2',5'-dione (sorbinil, CP-45,634), an aldose reductase inhibitor with potential utility in the treatment of chronic diabetic complications, are described. Tritiated sorbinil was prepared by a reductive dehalogenation of the 8-chloro substituted analog with (H2)-H-3. C-14-labelled CP-45,634 was prepared using a Bucherer-Bergs synthesis of the racemic hydantoin beginning with 2,3-dihydro-6-fluoro-4H-1-benzopyran-4-one and C-14-potassium cyanide, followed by brucine resolution to isolate the pharmacologically active S-(+)-enantiomer.