Synthesis and biodistribution of [4-14C]-5-bromo-6-methoxy-5,6-dihydro-prodrug derivatives of 5-ethyl-2'-deoxyuridine.

The radiochemical syntheses of the [4-14C]-(-)-trans-(5S,6S)-5-bromo-5- ethyl-6-methoxy-5,6-dihydro-2'-deoxyuridine [2,(5S,6S)-BMEDU] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6- methoxy-5,6-dihydro-2'-deoxyuridine [3,(5R,6R)-BMEDU] are reported. These BMEDU diastereomers were synthesized in 21 and 25% radiochemical yield, respectively, by direct addition of methyl hypobromite to the 5,6-olefinic bond of [4-14C]-5-ethyl-2'-deoxyuridine (EDU). The biodistributions of [4-14C]-labelled diastereomers of 2 and 3, and EDU were determined in male Balb-C mice. The uptake of radioactivity in brain after injection of [4-14C]-BMEDU diastereomers of 2 and 3 was not significantly different than that of [4-14C]-EDU (P > 0.05). However, clearance of radioactivity from blood was substantially faster after injection of [4-14C]-EDU relative to the [4-14C]-BMEDU diastereomers. Liver samples, obtained after injection of the [4-14C]-BMEDU diastereomers, showed a higher percentage uptake of the injected dose per gram of tissue relative to liver samples obtained after injection of [4-14C]-EDU.