Synthesis of polynucleotides which contain 3,N4-ethanocytidine, a nucleoside modification resulting from the action of bis(chloroethyl)-nitrosourea

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

“…In order to ascertain the possible alkylation products of DNA, a number of studies ,− were devoted to the reactions of CENU analogs with synthetic polynucleotides and with DNA. Experimentally, the polynucleotides were incubated − with 14 C-labeled CENU and then digested to the monomer level so that modified nucleosides and heterobases could be separated and identified.…”

“…The compounds 1040 728,729 and 1041 730 were isolated from reactions of BCNU with nucleotides and DNA. The N2-3-ethanoguanine ( 1039 ) was isolated from CCNU-treated DNA . Compound 1040 was considered 729 to be a model for DNA intrastrand cross-links and compound 1041 a model 730 for interstrand cross-links.…”

“…Compound 733 was formed from 730 by an incubation for 5 h at 37 °C. 528 In contrast, 5′-amino-5′deoxythymidine (734), the hydrolysis product of 5′-CTNU (732), failed to inhibit the L1210 cell replication. 526 The cytotoxicity of 733 could be explained 527 by a selective inhibition of DNA metabolism of the L1210 leukemia cells.…”

“…The N2-3ethanoguanine (1039) was isolated from CCNUtreated DNA. 732 Compound 1040 was considered 729 to be a model for DNA intrastrand cross-links and compound 1041 a model 730 for interstrand cross-links. Syntheses of 1041a and 1041b were achieved by the reactions of 2-deoxycytidine with 6-(2-fluoroethyl)guanine 736 and 6-(2-fluoroethyl)-2-deoxyguanosine, 737 respectively.…”