New Approach to the Synthesis of N7‐Arylguanines and N7‐Aryladenines

Keder, Roman; Dvořáková, Hana; Dvořák, Dalimil

doi:10.1002/ejoc.200801002

Cited by 20 publications

(17 citation statements)

References 40 publications

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“…[D 5 ]7-PhG was similarly synthesized with [D 5 ]phenylboronic acid (Cambridge Isotope Laboratories, Inc.). Both compounds were purified by collection from HPLC and identified by their spectral properties, consistent with those reported [13]: 7-PhG: 1 H NMR (DMSO-D 6 ) δ 10.97 (s, 1H, NH), 8.29 (s, 1H, C8-H), 7.48 (m, 5H, PhH), 6.34 (s, 2H, NH 2 ); MS (positive ESI) m/z 228, [M + H] + ; UV (65% 15 mM NH 4 OAc in 35% aq CH 3 CN) λ max 230, 292 nm; [D 5 ]7-PhG: 1 H NMR (DMSO-D 6 ) δ 10.85 (s, 1H, NH), 8.23 (s, 1H, C8-H), 6.21 (s, 2H, NH 2 ); MS (positive ESI) m/z 233 [M + H] + ; UV (65% 15 mM NH 4 OAc in 35% aq CH 3 CN) λ max 230, 292 nm.…”

Section: Methodssupporting

confidence: 65%

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Toward optimal menu design

Bailly

Oulasvirta

2014

interactions

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Benzene oxide, the initial metabolite of the human carcinogen benzene, reacts with DNA producing 7-phenylguanine (7-PhG) and other products. We developed a highly sensitive liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry-parallel reaction monitoring method for the analysis of 7-PhG in DNA. Accuracy and precision of the method were established and the detection limit was about 8amol of 7-PhG injected on the column and less than 1 adduct per 10(9) nucleotides in DNA. 7-PhG was detected in calf thymus DNA reacted with 1μM to 10mM benzene oxide. The method was applied for the analysis of DNA isolated from bone marrow, lung, and liver of B6C3F1 mice treated by gavage with 50mg/kg benzene in corn oil 5 times weekly for 4weeks. 7-PhG was not detected in any of these DNA samples. The method was applied to DNA from mouse hepatocytes exposed to 100μM benzene oxide and human TK-6 lymphoblasts exposed to 100μM, 1, and 10mM benzene oxide. 7-PhG was only detected in TK-6 cell DNA from the 10mM exposure. The method was also applied to leukocyte DNA from 10 smokers and 10 nonsmokers. 7-PhG was detected in only one DNA sample, from a nonsmoker. The results of this study do not support the hypothesis that the benzene oxide-DNA adduct 7-PhG is involved in carcinogenesis by benzene.

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Section: Methodssupporting

confidence: 65%

“…7-PhG was synthesized in 3 steps by protection of the N 2 position of guanine, reaction with phenylboronic acid, and deprotection, as described previously [13]. [D 5 ]7-PhG was similarly synthesized with [D 5 ]phenylboronic acid (Cambridge Isotope Laboratories, Inc.).…”

Section: Methodsmentioning

confidence: 99%

Toward optimal menu design

Bailly

Oulasvirta

2014

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“…Published procedures were used for syntheses of BO (Henderson et al, 2005) and all authentic standards used, namely, PhMA Krouželka and Linhart, 2009a), 7-PhG (Keder et al, 2009), 3-phenyladenine (3-PhA) (Krouželka and Linhart, 2009b) and N 6 -phenyladenine (6-PhA) (Laufer et al, 2005). It was critically important to purify BO by distillation in a vacuum before use.…”

Section: Methodsmentioning

confidence: 99%

Reactions of benzene oxide, a reactive metabolite of benzene, with model nucleophiles and DNA

Míčová

Linhart

2012

Xenobiotica

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1. Reactivity of benzene oxide (BO), a reactive metabolite of benzene, was studied in model reactions with biologically relevant S- and N-nucleophiles by LC-ESI-MS. 2. Reaction with N-acetylcysteine (NAC) in aqueous buffer solutions gave N-acetyl-S-(6-hydroxycyclohexa-2,4-dien-1-yl)cysteine (pre-phenylmercapturic acid, PPhMA), which was easily dehydrated in acidic solutions to phenylmercapturic acid (PhMA). The yield of PPhMA + PhMA increased exponentially with pH up to 11% in the pH range from 5.5 to 11.4. 3. Primary 6-hydroxycyclohexa-2,4-dien-1-yl (HC) adducts were detected also in reactions of purine nucleosides and nucleotides under physiological conditions. After a vigorous acidic hydrolysis, all HC adducts were converted to corresponding phenyl purines, which were identified as 7-phenylguanine (7-PhG), 3-phenyladenine (3-PhA) and N(6)-phenyladenine (6-PhA). The yield of 7-PhG amounted to 14 ± 5 and 16 ± 7 ppm for 2'-deoxyguanosine and 2'-deoxyguanosine-5'-monophosphate, respectively, that of 6-PhA was 500 ± 70 and 455 ± 75 ppm with 2'-deoxyadenosine and 2'-deoxyadenosine-5'-phosphate, respectively, with only traces of 3-PhA. 4. Reactions with the DNA followed by acidic hydrolysis yielded 26 ± 11 ppm (mean ± SD; n = 9) of 7-PhG as the sole adduct detected. 5. In contrast to the reactions with S-nucleophiles, the reactivity of BO with nucleophilic sites in the DNA is very low and can therefore hardly account for a significant DNA damage caused by benzene.

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“…[11] Nevertheless,t he direct coupling of purines in ac hemo-, regio-and enantioselective manner is still underdeveloped. To control the selectivity,m ethodologies based on the use of metal salts, [15] Vorbrüggen conditions [16] and transition-metalcatalyzed reactions [17] are known, but scope and conditions are limiting.A dditionally,p urines show ap ersistent insolubility and poor nucleophilicity in organic solvents,making the reaction very challenging. Linear and branched products as well as the corresponding N 9 /N 7 substituted products may arise during the hydroamination process (Scheme 1).…”

mentioning

confidence: 99%

Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir

Thieme

Breit

2017

Angew Chem Int Ed

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The rhodium-catalyzed atom-economic asymmetric N-selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio- and E/Z-selectivity with a Pd/dppf catalyst system. Furthermore, the new methodology was applied to a straightforward asymmetric synthesis of carbocyclic nucleoside abacavir.

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New Approach to the Synthesis of N⁷‐Arylguanines and N⁷‐Aryladenines

Cited by 20 publications

References 40 publications

Toward optimal menu design

Toward optimal menu design

Reactions of benzene oxide, a reactive metabolite of benzene, with model nucleophiles and DNA

Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir

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