Synthesis of 3′-CTNU radiolabelled with 14C in the alkylating moiety and 3H in the carbamoylating moiety

Abstract

[6-3H]3′-[3-(2-Chloroethyl)-3-nitrosoureido]-3′-deoxythymidine ([3H]3′-CTNU) radiolabelled with 3H in the carbamoylating moiety has been synthesized in high yield by conversion of tritiated 3′-amino-3′-deoxythymidine([3H]3′-ATdR) to [6-3H]3′-[3-(2-chloroethylureido)]-3′-deoxythymidine ([3H]3′-UTdR), followed by nitrosation with N2O3 gas. The title compound radiolabelled with 14C in the alkylating moiety was prepared by conversion of [2-14C]ethanolamine hydrochloride to [1-14C]chloroethylamine hydrochloride, followed by reaction with phosgene to yield [1-14C] chloroethyl isocyanate. This was converted to 3′-3-([1-14C] 2-chloroethylureido)-3′-deoxythymidine([14C]3′-UTdR), and nitrosated to afford 3′-[3-([1-14C] 2-chloroethyl) -3-nitrosoureido]-3′-deoxythymidine ([14C]3′-CTNU). HPLC methodology was developed for the purification of intermediate and final products.