- The pH effect on the naphthoquinone-photosensitized oxidation of 5-methylcytosine
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The pH effect on the one-electron photooxidation of 5-methyl-2′- deoxycytidine (dmC) by sensitization with 2-methyl-1,4-naphthoquinone (NQ) was investigated. Photoirradiation of an aqueous solution containing dmC and NQ under slightly acidic conditions of pH 5.0 efficiently produced 5-formyl-2′-deoxycytidine, whereas similar NQ-photosensitized oxidation of dmC proceeded to a lesser extent under more acidic or basic conditions. Fluorescence-quenching experiments re vealed that the less-efficient photooxidation at pH values below 4.5 is attributed to the decreased rate of one-electron oxidation of dmC owing to protonation at the N(3)-position. The NQ-photosensitized oxidation of an N(4)-dimethyl-substituted dmC derivative under various pH conditions also sug gests that the pH change in the range of 5.0 to 8.0 may be responsible for a reversible deprotonation-protonation equilibrium at the N(4)-exocyclic amino group of the dmC radical cation. In accord with the photochemical reactivity of monomeric dmC, the 5-methylcytosine residue in oligodeoxynucleotides was oxidized efficiently by photoexcited NQ-tethered oligodeoxynucleotides under slightly acidic conditions to form an alkali-labile 5-formylcytosine residue.
- Yamada, Hisatsugu,Tanabe, Kazuhito,Ito, Takeo,Nishimoto, Sei-Ichi
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- Facile functionalization at the C4 position of pyrimidine nucleosides via amide group activation with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and biological evaluations of the products
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Reactions of O-t-butyldimethylsilyl-protected thymidine, 2′-deoxyuridine, and 3′-azidothymidine (AZT) with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) leads to activation of the C4 amide carbonyl by formation of putative O4-(benzotriazol-1-yl) derivatives. Subsequent substitution with alkyl and aryl amines, thiols, and alcohols leads to facile functionalization at this position. Reactions with amines and thiols were conducted either as a two-step, one-pot transformation, or as a one-step conversion. Reactions with alcohols were conducted as two-step, one-pot transformations. In the course of these investigations, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the pyrimidine nucleosides was identified. However, these too underwent conversion to the desired products. Products obtained from AZT were converted to the 3′-amino derivatives by catalytic reduction. All products were assayed for their abilities to inhibit cancer cell proliferation and for antiviral activities. Many were seen to be active against HIV-1 and HIV-2, and one was active against herpes simplex virus-1 (HSV-1).
- Akula, Hari K.,Kokatla, Hariprasad,Andrei, Graciela,Snoeck, Robert,Schols, Dominique,Balzarini, Jan,Yang, Lijia,Lakshman, Mahesh K.
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p. 1130 - 1139
(2017/02/10)
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