Synthesis of C8-Adenosine Adducts of Arylamines Using Palladium Catalysis

Schoffers, Elke; Olsen, Phil; Means, Jay C.

doi:10.1021/ol016900h

Cited by 34 publications

(36 citation statements)

References 26 publications

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“…Our lab and others have utilized this reaction for the synthesis of C8-arylamine adducts of dGuo (33,36,(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). The C8-dGuo adducts of IQ and AF were synthesized using this chemistry and incorporated into oligonucleotides via their phosphoramidite.…”

Section: Discussionmentioning

confidence: 99%

Conformational Differences of the C8-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) within the NarI Recognition Sequence

Elmquist

Wang

Stover

et al. 2007

Chem. Res. Toxicol.

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Abstract2-Amino-3-methylimidazo [4,5-f]quinoline (IQ) is a highly mutagenic heterocyclic amine found in cooked meats. The major DNA adduct of IQ is at the C8-position of dGuo. We have previously reported the incorporation of the C8-IQ adduct into oligonucleotides, namely, the G 1 -position of codon 12 of the N-ras oncogene sequence (G 1 G 2 T) and the G 3 -position of the NarI recognition sequence (G 1 G 2 CG 3 CC) (Elmquist et al. (2004) J. Am. Chem. Soc. 126, 11189-11201). Ultraviolet spectroscopy and circular dichroism studies indicated that the conformation of the adduct in the two oligonucleotides was different, and they were assigned as groove-bound and base-displaced intercalated, respectively. The conformation of the latter was subsequently confirmed through NMR and restrained molecular dynamics studies (Wang et al. (2006) J. Am. Chem. Soc. 128, 10085-10095). We report here the incorporation of the C8-IQ adduct into the G 1 -and G 2 -positions of the NarI sequence. A complete analysis of the UV, CD, and NMR chemical shift data for the IQ protons are consistent with the IQ adduct adopting a minor groove-bound conformation at the G 1 -and G 2 -positions of the NarI sequence. To further correlate the spectroscopic data with the adduct conformation, the C8-aminofluorene (AF) adduct of dGuo was also incorporated into the NarI sequence; previous NMR studies demonstrated that the AF-modified oligonucleotides were in a sequence-dependent conformational exchange between major groove-bound and base-displaced intercalated conformations. The spectroscopic data for the IQ-and AF-modified oligonucleotides are compared. The sequence-dependent conformational preferences are likely to play a key role in the repair and mutagenicity of C8-arylamine adducts.

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Section: Discussionmentioning

confidence: 99%

Conformational Differences of the C8-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) within the NarI Recognition Sequence

Elmquist

Wang

Stover

et al. 2007

Chem. Res. Toxicol.

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“…Because of their low nucleophilicity, electron-deficient anilines are typically difficult substrates to employ in C-N cross-coupling or S N Ar reactions. of Cs 2 CO 3 , 2 mol-% of Pd 2 (dba) 3 , and 6 mol-% of Xantphos in dry dioxane in a sealed tube at 120°C led to high yields of 8-aminated purines 8 in 57-89 % yield (Table 3). The use of 1.2 equiv.…”

Section: Resultsmentioning

confidence: 99%

“…of amine in the presence of 1.5 equiv. [41] As an example, we treated p-MeO-phenyl boronic acid with 8a in the presence of copper(I) thiophene-2-carboxylate (CuTC) and a palladium catalyst [Pd 2 (dba) 3 ] under Liebeskind conditions. Again, this reaction proceeded equally well with arylamines bearing electron-withdrawing and electron-donating substituents.…”

Section: Resultsmentioning

confidence: 99%

Palladium‐Catalyzed Amidation and Amination of 8‐Iodopurine

et al. 2012

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“…The per-deutero-and non-labeled N-(adenin-8-yl)-2-aminofluorene and N-(adenin-8-yl)-benzidine were prepared using our new method of palladium catalysis [26]. The specifics of the synthesis for the per-deutero compounds are to be published in a separate manuscript.…”

Section: Reagentsmentioning

confidence: 99%

Development of an isotope dilution liquid chromatography/tandem mass spectrometry detection method for DNA adducts of selected aromatic amines

Means

Olsen

Schoffers

2003

J. Am. Soc. Mass Spectrom.

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Polycyclic aromatic amines (arylamines) are a class of chemical carcinogens that are prevalent in environmental and industrial settings. They are metabolically activated to covalently bond to DNA, forming mutagenic adducts. In order to study the mechanisms of their toxicity, sensitive and selective quantitative LC/MS/MS detection methods were developed to measure the N-(adenin-8-yl)-benzidine adduct and N-(adenin-8-yl)-2-aminofluorene in total DNA extract samples. A novel synthetic method using a palladium catalyst was previously developed to prepare authentic and deuterated arylamine-adenine adducts to serve as standards. These standards were then used to develop an HPLC electrospray ionization tandem mass spectrometry, isotope dilution method. Sample detection limits in DNA samples were 22 pg on-column and 51 pg on-column for the N-(adenin-8-yl)-benzidine-and N-(adenin-8-yl)-2-aminofluorene-adenine adducts, respectively. This method has applications for the study of DNA adduct formation as a biological marker of exposure to carcinogens and for environmental and workplace monitoring of these aromatic amines. (J Am Soc Mass

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Synthesis of C8-Adenosine Adducts of Arylamines Using Palladium Catalysis

Abstract: We employed palladium-catalyzed coupling procedures for the synthesis of new C8-adenosine adducts of various arylamines (aniline, benzidine, 4-aminobiphenyl, and 2-aminofluorene).[reaction: see text]

Cited by 34 publications

References 26 publications

Conformational Differences of the C8-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) within the NarI Recognition Sequence

Conformational Differences of the C8-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) within the NarI Recognition Sequence

Palladium‐Catalyzed Amidation and Amination of 8‐Iodopurine

Development of an isotope dilution liquid chromatography/tandem mass spectrometry detection method for DNA adducts of selected aromatic amines

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