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

Abstract

6-3Hl 3 I-13-(2-Chloroethyl) -3-nitrosoureidol -3 I-deoxythymidine( r3H1 3I-CTNU) radiolabelled with 'H in the carbamoylating moiety has been synthesized in hi h yield by conversion of (2-chloroethylureido) 1 -3'-deoxythymidine (r3H1 3'-UTdR), followed by nitrosation with N2O3 gas.The title compound radiolabelled with 14C in the alkylating moiety was prepared by conversion of t 2-14Clethanolamine hydrochloride to [1-14C1 chloroethylamine h drochloride, followed by reaction with phosgene to yield t1-' ' 1 2 1 chloroethyl isocyanate. This was converted to 3 ' -[ 3 -( 11-14C1 2-chloroethylureido)I-3'-deox thymidine([14C1 3'-UTdR), and nitrosated t o afford 3 ' -[ 3 -( t l-"CI 2-chloroethyl) -3-nitrosoureidol -3'-deoxythymidine ([l4C1 3I-CTNU). HPLC methodology was developed for t h e purification of intermediate and final products.

A Critical Appraisal of the Evolution ofN-Nitrosoureas as Anticancer Drugs

“…The C5‘ analogs 731 and 732 had low alkylating activities but only 732 was cytotoxic. Radiolabeled analogs of 732 containing 14 C in the CENU group, the alkylating moiety, and 3 H in the pyrimidine base, the carbamoylating moiety, were reported …”

“…Radiolabeled analogs of 732 containing 14 C in the CENU group, the alkylating moiety, and 3 H in the pyrimidine base, the carbamoylating moiety, were reported. 525 Several interesting papers [526][527][528][529] were concerned with the biological activity of the precursor compounds to the CENU thymidine analogs 730 and 732. Thus, 3′-amino-3′-deoxythymidine 733 (Chart 20), a hydrolysis product of 3′-CTNU 730, was shown 526,527 to be a potent inhibitor of L1210 cell replication.…”