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Synlett 2005(15): 2281-2284  
DOI: 10.1055/s-2005-872262
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Optical Properties of the C-8 Adduct of Benzo[a]pyrene and Deoxyguanosine

Linda Valis, Hans-Achim Wagenknecht*
Chemistry Department, Technical University of Munich, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913210; e-Mail: Wagenknecht@ch.tum.de;
Further Information

Publication History

Received 10 June 2005
Publication Date:
03 August 2005 (online)

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Abstract

8-(Benzo[a]pyren-6-yl)-2′-deoxyguanosine (Bp-dG) was prepared via a palladium-catalyzed Suzuki-Miyaura-type cross-coupling reaction from the pinacol ester of 6-benzo[a]pyrenyl boronic acid and the corresponding brominated deoxyguanosine precursor. The absorption and steady-state fluorescence properties of Bp-dG were characterized and compared with that of 6-benzo[a]pyrene. The modified nucleoside Bp-dG exhibits an unexpected high stability towards nucleosidic hydrolysis even under irradiation with UV light.

Key words

DNA damage - nucleoside - cross-coupling - palladium - pyrene

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The crude product was purified by column chromatography on silica gel (hexane-toluene = 1:1) yielding a yellow solid (25%). R f = 0.23 (hexane-toluene = 1:1). 1H NMR (500 MHz, CDCl3): δ = 9.08 (m, 2 H), 8.67 (m, 1 H), 8.44 (d, J = 9.0 Hz, 1 H), 8.35 (d, J = 9.0 Hz, 1 H), 8.24 (d, J = 7.5 Hz, 1 H), 8.10 (d, J = 7.5 Hz, 1 H), 7.97 (m, 2 H), 7.81 (m, 2 H), 1.66 (s, 12 H). 13C NMR (125 MHz, CDCl3): δ = 135.17, 134.82, 131.72, 131.58, 129.48, 129.14, 128.80, 128.65, 128.49, 128.16, 126.55, 126.36, 126.11, 126.0, 125.76, 125.42, 123.62, 123.57, 122.59, 85.03, 25.68. HRMS (EI): m/z calcd for C26H23O2B: 378.17911; found: 378.17896.

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The crude product was purified by column chromatography on silica gel (CH2Cl2-acetone = 4:1, then EtOAc-MeOH = 10:1, then EtOAc-MeOH-H2O = 10:1:0.5) yielding a yellow solid (25%). Analytical HPLC (RP-18 column, gradient A:B = 10:90 to 90:10 over 45 min, A = MeCN, B = H2O) was performed to ensure the purity of 1 of >99.5%. R f = 0.40 (EtOAc-MeOH-H2O = 10:1:0.5). NMR signals were assigned based on 2D NMR measurements (HSQC). 1H NMR (500 MHz, DMSO-d 6): δ = 10.90 (br s, 1 H, NH), 9.34 (m, 2 H, H-10, H-11), 8.57 (d, J = 9.2 Hz, 1 H, H-12), 8.45 (d, J = 7.9 Hz, 1 H, H-1), 8.27 (d, J = 7.4 Hz, 1 H, H-3), 8.08 (m, 2 H, H-2, H-4), 7.91 (m, 1 H, H-9), 7.83 (m, 1.5 H, H-8, H-7), 7.61 (d, J = 8.3 Hz, 0.5 H, H-7), 7.55 (d, J = 9.5 Hz, 0.5 H, H-5), 7.40 (d, J = 9.5 Hz, 0.5 H, H-5), 6.53 (br s, 2 H, NH2), 5.47 (m, 1 H, H-1′), 4.36 (m, 1 H, H-3′), 3.76 (m, 1 H, H-4′), 3.58 (m, 1 H, H-5′), 3.46 (m, 1 H, H-5′), 2.81 (m, 1 H, H-2′), 1.70 (m, 1 H, H-2′). 13C NMR (125 MHz, DMSO-d 6): δ = 157.49, 156.30, 154.27, 132.58 (C-7), 130.02 (C-12), 130.33 and 127.83 (C-4 and C-2), 128.05, 127.75 (C-1), 127.08 (C-3), 127.66 (C-9), 126.05, 125.93 (C-5), 123.43 and 124.94 (C-10 and C-11), 121.35, 88.80 (C-4′), 85.97 (C-1′), 71.93 (C-3′), 62.94 (C-5′), 37.39 (C-2′). HRMS (ESI/FTICR): m/z calcd for C30H23N5O4 [M+ + H]: 518.18228; found: 518.18207.

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Steady-state fluorescence spectroscopy was performed at r.t. on a Spex Fluoromax III spectrometer. The emission spectra are corrected according to detection system variation with wavelength. UV/Vis absorbance spectroscopy was performed at r.t. on a Varian Cary 100 photometer. Dry solvents (Fluka puriss. over molecular sieve, H2O <0.01%) were used for the measurements.