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Synlett 2002(5): 0687-0691
DOI: 10.1055/s-2002-25349
LETTER
© Georg Thieme Verlag Stuttgart · New York

Preparation of Pyrenyl-Modified Nucleosides via Suzuki-Miyaura Cross-Coupling Reactions

Nicole Amann, Hans-Achim Wagenknecht*
Technical University of Munich, Institute for Organic Chemistry and Biochemistry, Lichtenbergstr. 4, 85747 Garching, Germany
Fax: +49(89)28913210; e-Mail: wagenknecht@ch.tum.de;
Further Information

Publication History

Received 29 January 2002
Publication Date:
07 February 2007 (online)

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Abstract

The modified nucleosides 5-pyrenyl-2′-deoxyuridine (1) and 8-pyrenyl-2′-deoxyguanosine (2) were synthesized via palladium-catalyzed Suzuki-Miyaura cross-coupling reactions of pyren-1-yl boronic acid (3) to either 5-iodo-2′-deoxyuridine (4), or 8-bromo-2′-deoxyguanosine (7), respectively. No protecting groups for the hydroxy and amino functions of the nucleoside are needed during the preparation. Both pyrene derivatives are suitable nucleoside models for the spectrosopic investigation of reductive electron transfer (in 1), or oxidative hole transfer (in 2).

Key words

charge transfer - nucleoside - cross-coupling - palladium - pyrene

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20

The crude product was purified by column chromatography on silica gel (CH2Cl2/acetone = 4:1 then EtOAc/MeOH = 10:1) yielding a pale yellow solid (70%). Analytical HPLC (RP-18 column, gradient A/B = 10:90 to 90:10 over 45 min, A = MeCN + 0.1% TFA, B = H2O + 0.1% TFA) was performed to ensure the purity of 1 of > 99.5%. Spectroscopical Data of 1: Rf = 0.65 (EtOAc/MeOH/H2O = 10:1:0.5). NMR signals were assigned based on 2D NMR measurements (DQF-COSY, HMQC). 1H NMR (500 MHz, CD3OD): δ = 2.29 (m, J = 6.4 Hz, 2 H, 2′-H), 3.50-3.60 (ddd, J = 12.0 Hz, 3.3 Hz, 2 H, 5′-H), 3.84 (m, J = 3.2 Hz, 1 H, 3′-H), 4.31 (m, J = 4.3 Hz, 1 H, 4′-H), 6.35 (t, J = 6.6 Hz, 1 H, 1′-H), 7.84-8.14 (m, 9 H, Pyren-H), 8.21 (s, 1 H, H-6) ppm; additional signals in 1H NMR (250 MHz, d 6-DMSO): δ = 4.79 (t, 1 H, 5′-OH), 5.24 (d, 1 H, 3′-OH), 11.64 (s, br, 1 H, NH) ppm. 13C{1H} NMR (75 MHz, CD3OD): δ = 174.87, 174.13, 167.41, 163.91, 153.37, 153.15, 144.63, 144.07, 134.89, 134.29, 134.13, 133.93, 131.21, 131.01, 130.45, 129.49, 127.94, 126.83, 103.76, 104.41, 90.16 (4′-C), 87.76 (1′-C), 73.42 (3′-C), 62.67 (5′-H), 42.52 (2′-C) ppm. ESI-MS: m/z = 429 [M + H]+, 451 [M + Na]+, 857 [2 M + H]+, 879 [2 M + Na]+.

22

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 (65%). Analytical HPLC (RP-18 column, gradient A/B = 10:90 to 90:10 over 45 min, A = MeCN + 0.1% TFA, B = H2O + 0.1% TFA) was performed to ensure the purity of 2 of > 99.5%. Rf = 0.73 (EtOAc/MeOH/H2O = 6:2:1). NMR signals were assigned based on 2D-NMR measurements (DQF-COSY, HMQC). 1H NMR (500 MHz, CD3OD): δ = 1.98 (m, J = 13.4 Hz, 5.8 Hz, 1 H, 2′-H), 3.05 (m, 1 H, 2′-H), 3.58-3.72 (m, J = 9.9 Hz, 8.9 Hz, 4.2 Hz, 3 H, 5′-H, 4′-H), 4.32 (m, 1 H, 3′-H), 5.75 (t, J = 7.5 Hz, 1 H, 1′-H), 7.99-8.27 (m, 9 H, Pyren-H) ppm; additional signals in 1H NMR (250 MHz, D6-DMSO): δ = 4.93 (m, 2 H, 5′-OH, 3′-OH), 6.47 (s br, 2 H, NH2), 10.87 (s br, 1 H, NH) ppm; no 13C NMR data could be obtained due to the low solubility of 2 in suitable NMR solvents. ESI-MS: m/z = 468 [M + H]+, 490 [M + Na]+, 936 [2 M + H]+, 959 [2 M + Na]+.

23

Steady-state fluorescence spectroscopy was performed at r.t. on a Spex Fluoromax II 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 50 photometer. Dry solvents (Fluka puriss. over molecular sieve, water < 0.01%) were used for the measurements. The septum-closed cuvettes were filled under argon.

24

Amann, N.; Pandurski, E.; Wagenknecht, H.-A.; Fiebig, T. in preparation.

26

Currently, time-resolved spectroscopic measurements on the femtosecond time scale are performed in order to detect and characterize the short-lived intermediates by their transient absorption: Amann, N.; Pandurski, E.; Wagenknecht, H.-A.; Fiebig, T. in preparation.