RCHH HARM
A P
Arch. Pharm. Chem. Life Sci. 2016, 349, 414–427
Chemopreventive Activities of Resveratrol Derivatives
Archiv der Pharmazie
–
morpholino-CH), 208 (292–CH2 CMe –Me–CO). Anal. calcd. for
C
132.25 (s), 130.30 (d), 129. 36 (d), 129.00 (d), 128.20 (d), 127.7
(s), 125.39 (s), 122.52 (s), 114.51 (d), 105.64 (d), 102.04 (d),
80.19 (d), 79.95 (d), 55.93 (q). 19F NMR (CDCl3), ꢁ72.15 (s, 3F),
ꢁ71.95 (s, 3F). ESIMS m/z: 759 (MþþNa), 525 [759–PhC(CF3)
(OCH3)C(O)OH)].
–
2
33H43O8N: C, 68.16; H, 7.40. Found: C, 68.34; H, 7.42.
1-(400-Pivaloyloxyphenyl)-2-(30,50-dipivaloyloxyphenyl)-1-
oxo-2-morpholinoethane (13)
Yield: 20%; 1H NMR (CDCl3): d 8.09 (d, 2H, J ¼ 8.8 Hz), 7.12 (d,
2H, J ¼ 8.8 Hz), 7.05 (d, 2H, J ¼ 2.0 Hz), 6.85 (dd, 1H, J ¼ 2.0,
2.0 Hz), 4.81 (s, 1H), 3.73 (m, 4H), 2.52 (m, 4H), 1.35 (s, 9H),
1.34 (s, 18H); EI-MS, m/z: 581 (Mþ), 376 (1-(3,5-dipivaloyloxy-
bis-MTPA-ester of (1R,2R)-1-(30,50-dimethoxyphenyl)-2-(400-
methoxyphenyl)-1,2-dihydroxyethane (19)
Colorless amorphous solid; yield: 88%; [a]D ¼ ꢁ28.41; 1H NMR
(CDCl3); d 7.4–7.25 (10 H), 7.09 (d, 2H, J ¼ 8.0 Hz), 6.76 (d, 2H,
J ¼ 8.0 Hz), 6.33 (t, 1H, J ¼ 4.0 Hz), 6.30 (d, 2H, J ¼ 4.0 Hz), 6.29
and 6.25 (AB system, 2H, J ¼ 8.0 Hz), 3.78 (s, 3H), 3.70 (s, 6H),
3.38 (s, 3H), 3.36 (s, 3H). 13C NMR (CDCl3), 166.24 (s), 161.28 (s),
160.55 (s), 137.53 (s), 132.44 (s), 130.23 (d), 130.18 (d), 129.52
(d), 128.98 (d), 128.29 (d), 128.19 (d), 127.32 (s), 125.24 (s),
122.38 (s), 114.42 (d), 105.83 (d), 102.00 (d), 79.34 (d), 79.09
(d), 55.89 (q). 19F NMR (CDCl3), ꢁ71.87 (s, 3F), ꢁ71.90 (s, 3F).
ESIMS m/z: 759 (MþþNa), 525 [759–PhC(CF3)(OCH3)C(O)OH)].
–
–
phenyl)-1-morpholino-CH), 305 (376–CH2 CMe –Me), 276
2
–
(376–O CCMe –Me).
–
3
1-(30-Pivaloyloxy-50-hydroxyphenyl)-2-(400-
pivaloyloxyphenyl)-1-oxo-2-morpholinoethane (14)
Colorless solid; Yield: 60%; 1H NMR (CDCl3): d 7.48 (d, 2H,
J ¼ 8.8 Hz), 7.05 (d, 2H, J ¼ 8.8 Hz), 6.78 (d, 2H, J ¼ 2.0 Hz), 6.5
(dd, 1H, J ¼ 2.0, 2.0 Hz) 4.91 (s, 1H), 3.75 (m, 4H), 2.52 (m, 4H),
1.35 (s, 18 H); EI-MS, m/z: 497 (Mþ). Anal. calcd. for C28H35O7N:
C, 67.61; H, 7.04. Found: C, 67.84; H, 7.06.
(1S,2S)-1-(30-Hydroxy,50-methoxyphenyl)-2-(400-
hydroxyphenyl)-1,2-dihydroxyethane (20)
1-(400-Pivaloyloxyphenyl)-2-(30-pivaloyloxy-50-
hydroxyphenyl)-1-oxo-2-morpholinoethane (15)
Colorless oil; yield: 55%; 1H NMR (DMSO-d6): d 9.75 (bs, 1H,
exchanged with D2O), 9.23 (bs, 1H, exchanged with D2O), 6.97
(s, 1H), 6.93 (s, 1H), 6.88 (d, 2H, J ¼ 8.8 Hz), 6.51 (d, 2H,
J ¼ 8.8 Hz), 6.49 (dd, 1H, J ¼ 2.0, 2.0 Hz), 5.17 (d, 2H, J ¼ 2.0 Hz),
3.68 (s, 3H); EI-MS, m/z: 276 (Mþ). Anal. calcd. For C15H16O5:
C, 65.22; H, 5.80. Found: C, C, 65.45; H, 5.81.
Yield: 20%; 1H NMR (CDCl3): d 8.07 (d, 2H, J ¼ 8.8 Hz), 7.42 (d,
2H, J ¼ 2.0 Hz), 7.12 (d, 2H, J ¼ 8.8 Hz), 6.72 (dd, 1H, J ¼ 2.0,
2.0 Hz), 4.81 (s, 1H), 3.73 (m, 4H), 2.52 (m, 4H), 1.34 (s, 18H).
(1S,2S)-1-(30,50-Dimethoxyphenyl)-2-(400-methoxyphenyl)-
1,2-dihydroxyethane (16a)
Colorless oil. Yield: 79%; [a]D ꢁ90.57° (CHCl3, c 0.1); 1H NMR
(1S,2S)-1-(30,50-Dimethoxyphenyl)-2-(400-methoxyphenyl)-
1,2-dihydroxyethane,1,2-carbonate (21)
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(CDCl3 þ D2O): d 7.10 (d, 2H, J ¼ 8.8 Hz), 6.80 (d, 2H, J ¼ 8.8 Hz),
6.32 (dd, 1H, J ¼ 2.0, 2.0 Hz), 6.29 (d, 2H, J ¼ 2.0 Hz), 4.64 (bs,
2H), 3.78(s, 3H), 3.70 (s, 6H). 13C NMR (CDCl3) dC (ppm):
2 ꢄ 160.42 (s), 159.262 (s), 142.55 (s), 132.19 (s), 2 ꢄ 128.12 (d),
2 ꢄ 113.562 (d), 2 ꢄ 104.90 (d), 100.05 (d), 78.02 (d), 77.75 (d),
3 ꢄ 55.23 (q); EI-MS, m/z: 304 (Mþ). Anal. calcd. for C17H20O5: C,
67.10; H, 6.58. Found: C, 67.36; H, 6.60.
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Colorless oil. Yield: 90%; [a]D
ꢁ18.44° (CHCl3, c 0.01);
1H NMR (CDCl3): d 7.26 (d, 2H, J ¼ 8.8 Hz), 6.97 (d, 2H,
J ¼ 8.8 Hz), 6.48 (dd, 1H, J ¼ 2.0, 2.0 Hz), 6.40 (d, 2H, J ¼ 2.0 Hz),
5.32 and 5.38 (2H, AB system, J ¼ 10.7 Hz), 3.84 (s, 3H), 3.77
(s, 6H). 13C NMR (CDCl3) dC (ppm): 3 ꢄ 55.28 (q), 84.95 (d),
85.29 (d), 94.76 (d), 101.06 (d), 2 ꢄ 103.48 (d), 2 ꢄ 114.15 (s),
2 ꢄ 114.49 (d), 127.97 (d), 128,30. MS, m/z: 330 (Mþ).
Anal. calcd. for C18H18O6: C, 65.46; H, 546. Found: C, 65.35,
H, 5.44.
(1S,2S)-1-(30,50-Benzyloxyphenyl)-2-(400-benzyloxyphenyl)-
1,2-dihydroxyethane (16b)
Colorless oil. Yield: 78%; 1H NMR (CDCl3): d 7. 48 (m, 15H), 7.06
(d, 2H, J ¼ 8.8 Hz), 6.87 (d, 2H, J ¼ 8.8 Hz), 6.51 (dd, 1H, J ¼ 2.0,
2.0 Hz), 6.40 (d, 2H, J ¼ 2.0 Hz), 5.04 (s, 2H), 4.91 (s, 4H), 4.61 (s,
2H). 13C NMR (CDCl3): d 2 ꢄ 159.67 (s), 158.56 (s), 2 ꢄ 142.39 (s),
2 ꢄ 136.85 (s), 3 ꢄ 132.35 (s), 15 ꢄ 127.99 (d), 2 ꢄ 127.48 (d),
2 ꢄ 114.55 (d), 2 ꢄ 106.12 (d), 101.96 (d), 79.1 (d), 78.5 (d),
3 ꢄ 70.06 (t); EI-MS, m/z: 532 (Mþ). Anal. calcd. for C35H32O5:
C, 78.95; H, 6.02. Found: C, 78.65; H, 6.02.
(1S,2R)-1-(30,50-Dimethoxyphenyl)-2-(400-methoxyphenyl)-
1-hydroxy,2-azidoethane (22)
Yield: 54%; 1H NMR (CDCl3): d 7.24 (d, 2H, J ¼ 8.8 Hz), 6.92 (d,
2H, J ¼ 8.8 Hz), 6.46 (d, 2H, J ¼ 2.0 Hz), 6.42 (dd, 1H, J ¼ 2.0,
2.0 Hz), 4.73 (bd, 1H, J ¼ 10.0 Hz), 4.63 (d, 1H, J ¼ 10.0 Hz), 3.84
(s, 3H), 3.78 (s, 6H), 2.1 (bs, 1H, disappears with D2O). EI-MS
(positive mode): 286 (Mþ – HN3), 283 (Mþ – H2O – N2), 270 (Mþ
– OH – N3), 257 (Mþ – 2 ꢄ Me – N3). Anal. calcd. for C17H19N3O4:
C, 62.01; H, 5.78. Found: C, 62.25; H, 5.80.
bis-MTPA-ester of (1S,2S)-1-(30,50-dimethoxyphenyl)-2-(400-
methoxyphenyl)-1,2-dihydroxyethane (17)
Colorless amorphous solid; yield: 92%; [a]D ¼ ꢁ35.46 (CHCl3,
c ¼ 1.71); 1H NMR (CDCl3): d 7.38 (2H, t, J ¼ 8 Hz), 7.30–7.21
(6H), 7.10 (d, 2H, J ¼ 8.0 Hz), 6.77 (d, 2H, J ¼ 8.0 Hz), 6.37 (t, 1H,
J ¼ 4.0 Hz), 6.31 (d, 2H, J ¼ 4.0 Hz), 6.17 and 6.13 (AB system,
2H, J ¼ 8.0 Hz), 3.78 (s, 3H), 3.70 (s, 6H), 3.44 (s, 3H), 3.40 (s, 3H).
13C NMR (CDCl3), 166.52 (s), 161.35 (s), 160.56 (s), 137.94 (s),
(1S,2R)-1-(400-Methoxyphenyl)-2-(30,50-dimethoxyphenyl)-
1-hydroxy,2-azidoethane (23)
1
Yield: 21%; H NMR (CDCl3): d 7.22 (d, H, J ¼ 8.8 Hz), 6.91 (d,
2H, J ¼ 8.8 Hz), 6.46 (d, 2H, J ¼ 2.0 Hz), 6.42 (dd, 1H, J ¼ 2.0,
2.0 Hz), 4.73 (bd, 1H, J ¼ 10.0 Hz), 4.55 (d, 1H, J ¼ 10.0 Hz),
3.84 (s, 3H), 3.76 (s, 6H), 1.6 (bs, 1H, disappears with D2O).
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