Studies on Cleavage of Modified DNA

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In order to investigate the reactivity of modified DNA,the alkali labile lesion (1), which is obtained by oxidation of deoxyribose at the C4' position, C4' modified nucleotide derivatives were synthesized and their reactivities were studied.1) C4' Selenated nucleotide derivative (2) was synthesized as a precursor of unstable 1 and the reaction of 2 with NBS gave 1 to show that 2 can be used as a proper precursor of 1.2) The nucleoside derivative (3), which might be involved in the base-catalyzed decomposition of the alkali labile lesion(1), was synthesized. Amine treatment of 1 produced a nucleotide fragment having 3'-phosphate termini and lactam. Especially under neutral and acidic conditions, amine treatment of 1 afforded lactam in good yield as well as nucleotide fragment. The reaction mechanism of the formation of nucleotide fragment and lactam from 1 was proposed, giving insight into the mechanism of the amine-induced degradation of the alkali labile lesion.3) NBS treatment of C4' selenated nucleotide derivative (4) afforded the C4' oxidized nucleotide derivative (5), a simple model of 1. The reaction of 5 with amine at pH8 gave lactam in 40% yield. This result showed that 1 might react with amine under physiological conditions to give lactam and nucleotide fragment via 5 membered amine intermediate.