Nuclear Magnetic Resonance Studies of the 4R and 4S Diastereomers of Spiroiminodihydantoin 2'-Deoxyribonucleosides: Absolute Configuration and Conformational Features

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• 作者：Boleslaw Karwowski ; Franç ; ois Dupeyrat ; Michel Bardet ; Jean-Luc Ravanat ; Piotr Krajewski ; Jean Cadet
• 刊名：Chemical Research in Toxicology
• 出版年：2006
• 出版时间：October 2006
• 年：2006
• 卷：19
• 期：10
• 页码：1357 - 1365
• 全文大小：198K
• 年卷期：v.19,no.10(October 2006)
• ISSN：1520-5010

文摘

The present study was aimed at gaining further insights into stereochemical and conformational featuresof the 4R and 4S diastereomers of spiroiminodihydantoin 2'-deoxyribonucleosides that have been shownto be the predominant singlet oxygen oxidation products of 2'-deoxyguanosine in aqueous solutions. Itmay be added that spiroiminodihydantoin derivatives are efficiently generated by one-electron and singletoxygen oxidation of the 8-oxo-7,8-dihydroguanine moiety of several nucleic acid components includingnucleosides, nucleotides, and oligonucleotides. The reported structural data on the pair of diastereomericspiroiminodihydantoin 2'-deoxyribonucleosides 1 and 2 are mostly inferred from extensive ¹H and ¹³CNMR analyses including two-dimensional nuclear Overhauser effect measurements performed in bothD₂O and dimethyl sulfoxide. This approach that has been shown previously to be suitable to assign thestereochemistry of the base moiety of oxidized pyrimidine nucleosides was completed by molecularmodeling and quantum mechanics studies. Thus, application of these two complementary approachestogether with the consideration of the results of a recent relevant quantum mechanic study has allowedthe assignment of the absolute stereoconfiguration of the C-4 carbon of diastereomers 1 and 2. In addition,information is provided on the conformational features of the 2-deoxyribose moiety and the orientationof the base around the N-glycosidic bond of both 2'-deoxyribonucleosides 1 and 2.