J. Novák, Z. Hasník, I. Linhart
FULL PAPER
H, CH3COO–), 5.23 (d, J = 10.7 Hz, 1 H, CH2), 5.80 (d, J =
17.6 Hz, 1 H, CH2), 6.75 (dd, J = 10.7, 17.6 Hz, 1 H, PhCH), 7.19
(d; 2 H; J = 8.3 Hz, Ph), 7.51 (d, J = 8 Hz, 2 H, 5 Hz, Ph), 7.91
(s, 1 H, C8-H) ppm. 13CNMR (75 MHz, [D6]DMSO): δ = 21.1
(CH3COO–), 114.0 (CH=CH2), 122.0 and 127.3 (aromatic CH),
134.1 and 152.4 (aromatic C), 135.9 (CH=CH2), 156.2 (C4),
Acknowledgments
Financial support though grants 310/03/0437 from the Grant
Agency of the Czech Republic and MSM 604 613 73 01 from the
Ministry of Education of the Czech Republic is gratefully acknowl-
edged.
159.7 (C6). ESI-MS: m/z
=
292 [M
+
K]+, 276
[M + Na]+, 254 [M + H]+. C13H11N5O·C2H4O2 (313.32): calcd. C
57.5, H 4.8, N 22.3; found C 57.8, H 5.0, N 22.8.
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O6-[4-(2-Hydroxyethyl)phenyl]guanine (23): Obtained by the reac-
tion of 9 with phenol 19. The crude product was purified by col-
umn chromatography on silica gel using CHCl3/MeOH/AcOH,
30:3:1 as an eluent. Procedures (i) and (ii) gave 90 mg (35%) and
27 mg (9%), respectively, of a white powder which was identified
as arylguanine 23, m.p. 232–236 °C. Rf (CHCl3/MeOH/AcOH,
30:3:1) = 0.28. UV: λmax = 292 nm (pH 1); 286 nm (pH 6.5); 292 nm
(pH 12). 1H NMR (300 MHz, [D6]DMSO): δ = 2.72 (t, J = 6.9 Hz,
2 H, PhCH2), 3.62 (t, J = 6.9 Hz, 2 H, CH2O), 4.66 (s, 1 H,
CH2OH), 7.10 (d, J = 8.5 Hz, 2 H, Ph), 7.24 (d, J = 8.6 Hz, 2 H,
Ph), 7.91 (s, 1 H, C8-H) ppm. 13C NMR (75 MHz, [D6]DMSO): δ
= 38.0 (CH2CH2OH), 62.7 (CH2OH), 113.6 (C5), 122.0 and 130.6
(aromatic CH), 137.0 and 151.4 (aromatic C), 140.0 (C8), 157.4
(C4), 160.0 (C2), 160.4 (C6). ESI-MS: m/z = 310 [M + K]+, 294
[M + Na]+, 272 [M + H]+. C13H13N5O2·H2O (289.30): calcd. C
54.0, H 5.2, N 24.2; found C 53.6, H 4.8, N 22.9.
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O6-(4-Carboxymethylphenyl)guanine (24): Obtained by procedure
(ii) by reacting 9 with phenolic acid 20. The crude product was
purified by column chromatography on silica gel using CHCl3/
MeOH/AcOH (30:3:1) as eluent. Arylguanine 24 (105 mg, 35%)
was obtained as a white powder, m.p. Ͼ 300 °C, Rf (CHCl3/MeOH/
AcOH, 30:3:1) = 0.23. UV: λmax = 292 nm (pH 1); 286 nm (pH
6.5); 290 nm (pH 12). 1H NMR ([D6]DMSO): δ = 3.44 (s, 2 H,
OCH2CO2); 6.27 (s, 2 H, NH2), 7.10 (d, J = 8.5 Hz, 2 H, Ph), 7.27
(d, J = 8.5 Hz, 2 H, Ph), 7.9 (s, 1 H, C8-H) ppm. 13C NMR
(75 MHz, [D6]DMSO): δ = 43.0 (PhCH2), 113.6 (C5), 121.9 and
131.1 (aromatic CH), 134.3 and 151.5 (aromatic C), 157.5 (C4),
160.4 (C6), 175.0 (COOH). ESI-MS: m/z = 324 [M + K]+, 308 [M
+ Na]+, 286 [M + H]+. C13H11N5O3·H2O (303.28): calcd. C 51.5,
H 4.3, 23.1; found C 51.1, H 4.3, N 22.9.
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
O6-(4-Ethoxycarbonylmethylphenyl)guanine (25): Obtained by pro-
cedure (ii) by reacting 9 with phenol 21. Crystallisation of the crude
product from chloroform afforded 82 mg (25%) of arylguanine 25.
White powder, m.p. 215–217 °C, Rf (CHCl3/MeOH/AcOH, 30:3:1)
= 0.56. UV: λmax = 292 nm (pH 1); 286 nm (pH 6.5); 290 nm (pH
12). 1H NMR ([D6]DMSO): δ = 1.19 (t, J = 7.15 Hz, 3 H,
CH2CH3), 3.68 (s, 2 H, OCH2CO2), 4.85 (q, J = 7.15 Hz, 2 H,
CH2CH3), 6.26 (s, 2 H, NH2), 7.17 and 7.30 (d,, J = 8.4 Hz 2+2
H, Ph); 7.93 (s, 1 H, C8–H) ppm. 13C NMR (75 MHz, [D6]DMSO):
δ = 14.8 (CH2CH3), 52.4 (CH2COOH), 61.0 (OCH2CH3), 114.4
(C5), 122.3 and 131.2 (aromatic CH), 131.7 (aromatic C), 152.2
(aromatic COH), 156.8 (C4), 160.4 (C6), 172.0 (COOH). ESI-MS:
m/z = 352 [M + K]+, 334 [M + Na]+, 314 [M + H]+.
HPLC-MS Analyses: The crude products of the reaction of 9 with
phenols 18–20 were dissolved in aqueous methanol and analysed
by HPLC-MS on a Phenomenex Luna 2 C18 column (250×2 mm;
particle size: 5 µm). The column was eluted with 5 mm ammonium
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a rate of
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O. M. Bakke, R. R. Scheline, Toxicol. Appl. Pharmacol. 1970,
170 µLmin–1. The concentration of methanol was increased lin-
early up to 100% within 25 min and than kept unchanged for an
additional 5 min. The effluent was introduced into an ESI chamber
and the ions formed were detected in the mass range of m/z = 150–
700.
16, 691–700.
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