3.2. Synthesis of Resveratrol Derivatives
(E)-1,3-Diethoxy-5-(4-ethoxystyryl)benzene (2a). Resveratrol (1) (15.0 g, 65.7 mmol) was dissolved in a solution of DMF (150 mL) and NaOH (8.9 g), and stirred for 10 min. Then, 1-bromoethane (25.8 g, 236.6 mmol) was added and the reaction was kept for 24 h at 40 °C. After the removal of DMF by evaporation under vacuum, the reaction mixture was extracted with toluene (45 mL × 2). The combined organic layer were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (95:5) as an eluent to give compound 2a (15.4 g, 75.0% yield). Compound 2a: IR νmax cm−1: 1587, 1509, 1247; 1H-NMR (400 MHz, CDCl3) δ 7.45 (2H, d, J = 8.4 Hz), 7.05 (1H, d, J = 16.4 Hz), 6.91 (2H, J = 8.4 Hz), 6.92 (1H, d, J = 16.0 Hz), 6.66 (2H, d, J = 2.4 Hz), 6.39 (1H, t, J = 2.0 Hz), 4.08 (6H, m), 1.45 (9H, m); 13C-NMR (100 MHz, CDCl3) δ 160.3, 158.8, 139.6, 129.8, 128.6, 127.8, 126.6, 114.7, 104.9, 100.5, 63.5, 14.9, 14.8; ESI-MS (positive mode) m/z: 313 [M + H]+, HRESIMS: m/z 313.1798 (calcd. for C20H25O3, 313.1798).
(E)-1,3-Dibutoxy-5-(4-butoxystyryl)benzene (2b). Resveratrol (1) (15.0 g, 65.7 mmol) was dissolved in a solution of DMF (150 mL) and NaOH (8.9 g), and stirred for 10 min. Then, 1-bromobuthane (30.6 g, 223.5 mmol) was added and the reaction was kept for 24 h at 40 °C. After the removal of DMF by evaporation under vacuum, the reaction mixture was extracted with toluene (45 mL × 2). The combined organic layer were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (95:5) as an eluent to give compound 2b (21.2 g, 81.5% yield). Compound 2b: IR νmax cm−1: 1589, 1509, 1385, 1294; 1H-NMR (400 MHz, CDCl3) δ 7.45 (2H, d, J = 8.4 Hz), 7.08 (1H, d, J = 16.4 Hz), 6.93 (2H, J = 8.4 Hz), 6.94 (1H, d, J = 16.0 Hz), 6.69 (2H, d, J = 2.4 Hz), 6.43 (1H, t, J = 2.0 Hz), 4.02 (6H, m), 1.83 (6H, m), 1.57 (6H, m), 1.05 (9H, m); 13C-NMR (100 MHz, CDCl3) δ 160.5, 159.0, 139.6, 129.8, 128.6, 127.7, 126.6, 114.7, 104.9, 100.5, 67.7, 31.5, 31.4, 19.4, 19.3, 13.9; ESI-MS (positive mode) m/z: 397 [M + H]+, HRESIMS: m/z 435.2296 (calcd. for C26H36KO3, 435.2296).
(E)-1,3-Bis(pentyloxy)-5-(4-(pentyloxy)styryl)benzene (2c). Resveratrol (1) (50.0 g, 219.1 mmol) was dissolved in a solution of DMF (200 mL). After adding NaOH (28.0 g) and KI (1.8 g), the reaction mixture was stirred for 5 min at RT. Then, 1-bromopentane (109.2 g, 223.5 mmol) was added and the reaction was kept for 12 h at 45 °C. After the removal of DMF by evaporation under vacuum, the reaction mixture was extracted with toluene (45 mL × 2). The combined organic layer were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (95:5) as an eluent to give compound 2b (21.2 g, 81.5% yield). Compound 2c: IR νmax cm−1: 1692, 1385, 1344; 1H-NMR (400 MHz, CDCl3) δ 7.47 (2H, d, J = 8.4 Hz), 7.07 (1H, d, J = 16.4 Hz), 6.93 (2H, J = 8.4 Hz), 6.94 (1H, d, J = 16.0 Hz), 6.68 (2H, d, J = 2.4 Hz), 6.42 (1H, brs), 4.00 (6H, m), 1.85 (6H, m), 1.48 (12H, m), 0.99 (9H, m); 13C-NMR (100 MHz, CDCl3) δ 160.5, 159.0, 139.6, 129.8, 128.6, 127.7, 126.6, 114.7, 104.9, 100.5, 68.0, 29.1, 29.0, 28.3, 28.2, 22.5, 14.1; ESI-MS (positive mode) m/z: 439 [M + H]+, HRESIMS: m/z 477.2761 (calcd. for C29H42KO3, 477.2765).
(E)-1,3-Bis(hexyloxy)-5-(4-(hexyloxy)styryl)benzene (2d). Resveratrol (1) (10.0 g, 43.8 mmol) was dissolved in a solution of DMF (100 mL) and NaOH (5.96 g), and stirred for 10 min. Then, 1-bromohexane (25.8 g, 236.6 mmol) was added and the reaction was kept for 24 h at 40 °C. After the removal of DMF by evaporation under vacuum, the reaction mixture was extracted with toluene (45 mL × 2). The combined organic layer were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (95:5) as an eluent to give compound 2d (16.3 g, 77.3% yield). Compound 2d: IR νmax cm−1: 1698, 1593, 1457, 1162; 1H-NMR (400 MHz, CDCl3) δ 7.45 (2H, d, J = 8.4 Hz), 7.06 (1H, d, J = 16.4 Hz), 6.91 (2H, J = 8.4 Hz), 6.92 (1H, d, J = 16.0 Hz), 6.67 (2H, d, J = 2.4 Hz), 6.42 (1H, t, J = 2.0 Hz), 4.00 (6H, m), 1.82 (6H, m), 1.52 (6H, m), 1.39 (12H, m), 0.97 (9H, m); 13C-NMR (100 MHz, CDCl3) δ 160.5, 158.9, 139.6, 129.8, 128.6, 127.7, 126.6, 114.7, 104.8, 100.5, 68.0, 31.6, 29.4, 29.3, 25.8, 25.7, 22.6, 14.0; ESI-MS (positive mode) m/z: 481 [M + H]+, HRESIMS: m/z 519.3235 (calcd. for C32H48KO3, 519.3235).
(E)-1,3-Bis(octyloxy)-5-(4-(octyloxy)styryl)benzene (2e). Resveratrol (1) (10.0 g, 43.8 mmol) was dissolved in a solution of DMF (100 mL) and NaOH (5.9 g), and stirred for 10 min. Then, 1-bromooctane (25.8 g, 236.59 mmol) was added and the reaction was kept for 24 h at 40 °C. After the removal of DMF by evaporation under vacuum, the reaction mixture was extracted with toluene (45 mL × 2). The combined organic layer were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (95:5) as an eluent to give compound 2e (21.0 g, 84.7% yield). Compound 2e: IR νmax cm−1: 1694, 1507, 1383, 1298; 1H-NMR (400 MHz, CDCl3) δ 7.45 (2H, d, J = 8.4 Hz), 7.06 (1H, d, J = 16.4 Hz), 6.91 (2H, J = 8.4 Hz), 6.92 (1H, d, J = 16.0 Hz), 6.66 (2H, d, J = 2.4 Hz), 6.40 (1H, t, J = 2.0 Hz), 4.00 (6H, m), 1.83 (6H, m), 1.50 (6H, m), 1.36 (24H, m), 0.94 (9H, m); 13C-NMR (100 MHz, CDCl3) δ 160.5, 158.9, 139.6, 129.8, 128.6, 127.7, 126.5, 114.7, 104.8, 100.5, 68.0, 31.8, 29.4, 29.3, 29.2, 26.1, 26.0, 22.6, 14.1; ESI-MS (positive mode) m/z: 565 [M + H]+, HRESIMS: m/z 603.4176 (calcd. for C38H60KO3, 603.4174).
(E)-5-(4-Acetoxystyryl)-1,3-phenylene diacetate (3a). Resveratrol (1) (5.0 g, 21.9 mmol) was dissolved in CH2Cl2 (40 mL) and kept cool at 10 °C. TEA (7.1 g, 70.1 mmol) and DMAP (0.26 g, 2.19 mmol) were added to the reaction mixture at 10 °C. Acetyl chloride (5.3 g, 67.9 mmol) was added carefully and the reaction was kept for 1 h at 10 °C. After adding distilled water (40 mL) to the reaction mixture, the CH2Cl2 fraction was extracted. The CH2Cl2 layers were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (30:1) as an eluent to give compound 3a (6.9 g, 88.2% yield). Compound 3a: IR νmax cm−1: 1759, 1707, 1532, 1124; 1H-NMR (500 MHz, CDCl3) δ 7.54 (2H, d, J = 8.5 Hz), 7.12 (4H, m), 7.08 (1H, J = 16.0 Hz), 6.98 (1H, d, J = 16.0 Hz), 6.85 (1H, d, J = 2.0 Hz), 2.33 (9H, s); 13C-NMR (100 MHz, CDCl3) δ 169.3, 169.0, 151.3, 150.4, 139.5, 134.4, 129.6, 127.6, 127.2, 121.9, 116.9, 114.4, 21.1; ESI-MS (positive mode) m/z: 377 [M + Na]+, HRESIMS: m/z 393.0734 (calcd. for C20H18KO6, 393.0734).
(E)-5-(4-(3-Methylbut-2-enoyloxy)styryl)-1,3-phenylene bis(3-methylbut-2-enoate) (3b). Resveratrol (1) (5.0 g, 21.9 mmol) was dissolved in CH2Cl2 (40 mL) and kept cool at 10 °C. TEA (7.3 g, 72.3 mmol) and DMAP (0.26 g, 2.2 mmol) were added to the reaction mixture at 10 °C. 3,3-Dimethylacroyl chloride (8.3 g, 70.1 mmol) was added carefully and the reaction was kept for 1 h at 10 °C. After adding distilled water (50 mL) to reaction mixture, the CH2Cl2 fraction was extracted. The CH2Cl2 layers were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (95:5) as an eluent to give compound 3b (6.9 g, 92.5% yield). Compound 3b: IR νmax cm−1: 1738, 1645, 1379, 1343; 1H-NMR (400 MHz, CDCl3) δ 7.50 (2H, dd, J = 7.2, 2.0 Hz), 7.11 (4H, m), 7.01 (1H, d, J = 16.4 Hz), 6.86 (1H, t, J = 2.0 Hz), 2.26 (9H, d, J = 1.2 Hz), 2.02 (9H, s); 13C-NMR (100 MHz, CDCl3) δ 164.7, 164.4, 160.4, 160.1, 151.4, 150.4, 139.3, 134.3, 129.4, 127.5, 127.2, 122.0, 116.8, 115.1, 115.0, 114.8, 27.7, 27.6, 20.6, 20.5; ESI-MS (positive mode) m/z: 497 [M + Na]+, HRESIMS: m/z 513.1672 (calcd. for C29H30KO6, 513.1673).
(E)-5-(4-(2-Ethylhexanoyloxy)styryl)-1,3-phenylene bis(2-ethylhexanoate) (3c). Resveratrol (1) (10.0 g, 43.8 mmol) was dissolved in CH2Cl2 (50 mL) and kept to cool at 10 °C. TEA (7.3 g, 72.3 mmol) and DMAP (0.54 g, 4.4 mmol) were added to the reaction mixture. After stirring at 10 °C, 2-ethylnexanoyl chloride (22.8 g, 140.2 mmol) was added carefully and the reaction was kept for 1 h at 10 °C. After adding distilled water (50 mL) to reaction mixture, the CH2Cl2 fraction was extracted. The CH2Cl2 layers were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (50:1) as an eluent to give compound 3c (25.2 g, 94.8% yield). Compound 3c: IR νmax cm−1: 1754, 1644, 1376, 1201; 1H-NMR (500 MHz, CDCl3) δ 7.52 (2H, d, J = 8.5 Hz), 7.11 (4H, m), 7.03 (1H, J = 16.0 Hz), 6.98 (1H, d, J = 16.0 Hz), 6.78 (1H, d, J = 2.0 Hz), 2.56 (3H, m), 1.87 (6H, m), 1.76 (8H, m), 1.07 (9H, m), 0.97 (12H, m); 13C-NMR (100 MHz, CDCl3) δ174.7, 174.4, 151.5, 150.5, 139.4, 134.3, 129.6, 127.6, 127.2, 121.9, 116.8, 114.3, 47.4, 47.3, 31.7, 31.6, 29.6, 25.5, 25.4, 22.6, 13.9, 11.9; ESI-MS (positive mode) m/z : 629 [M + Na]+, HRESIMS: m/z 645.3550 (calcd. for C38H54KO6, 645.3551).
(E)-5-(4-(Octanoyloxy)styryl)-1,3-phenylene dioctanoate (3d). Resveratrol (1) (5.0 g, 21.9 mmol) was dissolved in CH2Cl2 (40 mL) and kept cool at 10 °C. TEA (7.1 g, 70.1 mmol) and DMAP (0.26 g, 2.2 mmol) were added to the reaction mixture. After stirring at 10 °C, octanoyl chloride (11.0 g, 67.9 mmol) was added carefully and the reaction was kept for 1 h at 10 °C. After adding distilled water (40 mL) to reaction mixture, the CH2Cl2 fraction was extracted. The CH2Cl2 layer were dried over anhydrous MgSO4 and evaporated under vacuum. The crude product was purified by silica gel column chromatography with n-hexane–EtOAc (30:1) as an eluent to give compound 3d (12.9 g, 96.7% yield). Compound 3d: IR νmax cm−1: 1758, 1644, 1367, 1267; 1H-NMR (500 MHz, CDCl3) δ 7.51 (2H, d, J = 8.5 Hz), 7.11 (4H, m), 7.08 (1H, J = 16.0 Hz), 6.99 (1H, d, J = 16.0 Hz), 6.82 (1H, d, J = 2.0 Hz), 2.58 (6H, m), 1.79 (6H, m), 1.34-1.42 (24H, m), 0.94 (12H, m); 13C-NMR (100 MHz, CDCl3) δ 172.2, 171.8, 151.4, 150.5, 139.4, 134.3, 129.6, 127.6, 127.2, 121.9, 116.8, 114.4, 34.4, 34.4, 31.6, 29.0, 28.9, 24.9, 24.8, 22.6, 14.0; ESI-MS (positive mode) m/z: 629 [M + Na]+, HRESIMS: m/z 645.3550 (calcd. for C38H54KO6, 645.3551).