Synthesis of Pyrene and Benzo[a]pyrene Adducts at the Exocyclic Amino Groups of 2‘-Deoxyadenosine and 2‘-Deoxyguanosine by a Palladium-Mediated C−N Bond-Formation Strategy

Synthesis of Pyrene and Benzo[a]pyrene Adducts at the Exocyclic Amino Groups of 2‘-Deoxyadenosine and 2‘-Deoxyguanosine by a Palladium-Mediated C−N Bond-Formation Strategy

Single-electron oxidation of the carcinogenic hydrocarbon benzo[a]pyrene (BaP) is thought to result in a radical cation intermediate and this species has been proposed to cause alkylation at the nitrogens of the purine nucleobases. Although several different nucleoside adducts have been isolated as...

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Bibliographic Details
Published in:Journal of organic chemistry Vol. 68; no. 15; pp. 6020 - 6030
Main Authors: Lakshman, Mahesh K, Ngassa, Felix N, Bae, Suyeal, Buchanan, Dennis G, Hahn, Hoh-Gyu, Mah, Heduck
Format: Journal Article
Language:English
Published: Washington, DC American Chemical Society 25-07-2003
Subjects:
Amines - chemistry
Benzo(a)pyrene - analogs & derivatives
Benzo(a)pyrene - chemical synthesis
Benzo(a)pyrene - chemistry
Carbohydrates. Nucleosides and nucleotides
Catalysis
Chemistry
Deoxyguanosine - chemistry
DNA Adducts
Exact sciences and technology
Indicators and Reagents
Magnetic Resonance Spectroscopy
Molecular Conformation
Nucleosides, nucleotides and oligonucleotides
Organic chemistry
Palladium
Preparations and properties
Pyrenes - chemical synthesis
Pyrenes - chemistry
Arylation
Amine
Amination
Pyrene derivatives
Aromatic compound
Palladium
NMR spectrometry
Deoxyribonucleoside
Ultraviolet spectrometry
Chemical synthesis
Chemical coupling
Halogen Organic compounds
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Summary:Single-electron oxidation of the carcinogenic hydrocarbon benzo[a]pyrene (BaP) is thought to result in a radical cation intermediate and this species has been proposed to cause alkylation at the nitrogens of the purine nucleobases. Although several different nucleoside adducts have been isolated as arising from this mode of metabolic activation, there are no selective, total syntheses of the stable exocyclic amino group adducts formed by the single-electron oxidation of any hydrocarbon with the purine 2‘-deoxynucleosides to date. In this paper we disclose the synthesis of the model adducts N 6-(1-pyrenyl)-2‘-deoxyadenosine and N 2-(1-pyrenyl)-2‘-deoxyguanosine as well as the first synthesis of the carcinogen-linked nucleoside derivatives N 6-(6-benzo[a]pyrenyl)-2‘-deoxyadenosine and N 2-(6-benzo[a]pyrenyl)-2‘-deoxyguanosine via a palladium-mediated C−N bond formation. Two different coupling strategies were attempted:  coupling of an aryl bromide with a suitably protected nucleoside and the coupling of an arylamine with a suitable halonucleoside. The former had somewhat limited applicability in that only N 6-(1-pyrenyl)-2‘-deoxyadenosine was prepared by this method; on the other hand, the latter was more general. However, there are noteworthy differences in the amination reactions at the C-6 and C-2 positions. Reactions at the C-6 resulted in the competing formation of a 1:2 amine−nucleoside adduct in addition to the desired monoaryl nucleoside. Such a dimer formation was not observed at the C-2. The C-2 adducts, however, displayed an interesting conformational behavior.
Bibliography:istex:732293305FF4994B3393396A527712D5D60C946F
ark:/67375/TPS-0TF46QRB-F
ISSN:0022-3263
1520-6904
DOI:10.1021/jo030113b