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

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

References

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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: R_f = 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%. R_f = 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.