DNA-nitrosourea interactions

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

“…The 2-haloethyl compounds 1033 and 1036 are capable of undergoing either intramolecular cyclization reactions to give derivatives 1035 712,723 and 1038 725 respectively, or a second alkylation reaction with another nucleoside, resulting in either interstrand or intrastrand cross-links. Syntheses of the bridged compound 1041, 736,737 and compounds related to 1041 738 have been reported. The compounds 1040 728,729 and 1041 730 were isolated from reactions of BCNU with nucleotides and DNA.…”

ChemInform Abstract: Formation of a Tricyclic Nucleoside from Deoxyguanosine via an O6,N1‐Transposition.

“…In principle the compound should be available through direct condensation of the activated deoxyguanosine derivative 2 [2] and chloroethanol, using DBU as strong base.Accordingly, the reaction of 2 with chloroethanol (3 equivalents) in presence of DBU (2.7 equivalents) in acetonitrile gave a disilylated nucleoside 3 (70% yield) which on deblocking (tetrabutylammonium fluorideltetrahydrofuran, rt, 1 hour and aqueous ammonia, 60°, 24 hours) yielded a new deoxynucleosidic compound 6. Its formation is rationnalised by an O'-N'-transposition.…”

“…In principle the compound should be available through direct condensation of the activated deoxyguanosine derivative 2 [2] and chloroethanol, using DBU as strong base. Heterocyclic Chem., 23, 969 (1986).…”

“…The 06-(2-hydroxyethy1)deoxyguanosine derivative 9 is available from the reaction of ethyleneglycol with 2 [2] (Scheme I). Reaction of chloroethanol with the activated However, this mechanism was corroborated by an additional experiment where we replaced the chlorine leaving group by a tosyloxy one.…”