2.1 Instruments
All other commercial reagents and solvents were used as received without further purification. Reaction solvents were distilled from calcium hydride for dichloromethane and from sodium metal and benzophenone for tetrahydrofuran. E-resveratrol (98%) was purchased from Shanxi Sciphar Hi-tech Industry Co., Ltd. (Shanxi, China). Reaction progress was monitored by thin-layer chromatography on silica gel GF254 with detection by ultraviolet (UV). Melting points were obtained using an X-4 binocular microscope melting point (mp) apparatus and are uncorrected. Yields were not optimized. 1H-NMR spectra and 13C-NMR spectra were recorded utilizing a Bruker AV400 spectrometer with CDCl3 as solvent and tetramethylsilane as internal standard. Chemical shifts (δ) were given in parts per million (ppm). High-resolution mass spectra (HRMS) data were obtained with a Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) spectrometer (ionspec, 7.0T).
2.2 General synthetic procedure for the target compounds I-1−I-10, II-1−II-5, and III-1−III-4 (Scheme 1)
E-resveratrol (0.1 g, 0.44 mmol) was dissolved in dichloromethane (20 mL), and Et3N (0.22 g, 2.19 mmol) was added. Then, PhCOCl (0.31 g, 2.19 mmol) were slowly added and the reaction mixture was stirred at room temperature. The progress of the reaction was monitored by TLC until the reaction was complete. Then the reaction mixture was added dichloromethane and water. The aqueous phase was separated and then extracted with dichloromethane twice. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtered. After the solvent was removed in vacuo, the residue was purified by column chromatography on silica gel to give the target compound I-1 as white solid.
Compounds I-2−I-10 (Scheme 2), II-1−II-5 (Scheme 3) and III-1−III-4 (Scheme 4) were synthesized according to the method used for compound I-1.
Data for (E)-5-(4-(benzoyloxy)styryl)-1,3-phenylene dibenzoate (I-1). White solid; yield 96%; mp 170–172 °C. 1H NMR (400 MHz, CDCl3) δ8.22 (m, 6H), 7.71–7.61 (m, 3H), 7.60–7.48 (m, 8H), 7.36–7.30 (m, 2H), 7.15 (m, 5H); 13C NMR (100 MHz, CDCl3) δ165.13, 164.86, 151.70, 150.73, 139.75, 134.56, 133.83, 133.70, 130.27, 130.23, 129.80, 129.45, 129.25, 128.68, 128.63, 127.78, 127.27, 122.09, 117.24, 114.82; HRMS (ESI) (m/z): calcd for C35H24O6 [M+NH4]+558.1911, found 558.1911.
Data for (E)-5-(4-((4-fluorobenzoyl)oxy)styryl)-1,3-phenylene bis(4-fluorobenzoate) (I-2). White solid; yield 81%; mp 167–169 °C. 1H NMR (400 MHz, CDCl3) δ8.28–8.20 (m, 6H), 7.56 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 2.0 Hz, 2H), 7.25–7.17 (m, 8H), 7.15–7.04 (m, 3H); 13C NMR (100 MHz, CDCl3) δ164.45 (d, J = 119 Hz, 1C), 164.14, 151.56, 150.62, 139.80, 134.59, 132.89 (d, J = 9 Hz, 1C), 132.90, 132.80, 129.87, 127.80, 127.24, 125.47, 122.05, 117.24, 116.05, 115.97, 115.83, 115.74, 114.72; HRMS (ESI) (m/z): calcd for C35H21F3O6 [M+NH4]+ 612.1628, found 612.1630.
Data for (E)-5-(4-((4-methylbenzoyl)oxy)styryl)-1,3-phenylene bis(4-methylbenzoate) (I-3). White solid; yield 80%; mp 159–161 °C. 1H NMR (400 MHz, CDCl3) δ8.14–8.07 (m, 6H), 7.55 (d, J = 8.4 Hz, 2H), 7.36–7.28 (m, 8H), 7.24–7.02 (m, 5H), 2.46 (s, 9H); 13C NMR (100 MHz, CDCl3) δ165.16, 164.89, 151.76, 150.79, 144.64, 144.50, 139.66, 134.50, 130.29, 130.26, 129.73, 129.38, 129.32, 127.72, 127.30, 126.72, 126.54, 122.10, 117.16, 114.86, 21.80; HRMS (ESI) (m/z): calcd for C38H30O6 [M+NH4]+ 600.2381, found 600.2379.
Data for (E)-5-(4-((4-chlorobenzoyl)oxy)styryl)-1,3-phenylene bis(4-chlorobenzoate) (I-4). White solid; yield 97%; mp 165–167 °C. 1H NMR (400 MHz, CDCl3) δ8.14–8.11 (m, 4H), 8.07 (d, J = 8.4 Hz, 2H), 7.55–7.47 (m, 9H), 7.30 (d, J = 2.0 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.13–7.04 (m, 2H); 13C NMR (100MHz, CDCl3) δ164.24, 163.96, 161.30, 151.51, 150.58, 141.42, 140.43, 140.26, 139.83, 134.61, 131.89, 131.60, 129.89, 129.38, 129.08, 129.00, 127.81, 122.00, 117.23, 114.62; HRMS (ESI) (m/z): calcd for C35H21Cl3O6 [M+NH4]+ 660.0742, found 660.0731.
Data for (E)-5-(4-((4-bromobenzoyl)oxy)styryl)-1,3-phenylene bis(4-bromobenzoate) (I-5). White solid; yield 85%; mp 183–185 °C. 1H NMR (400 MHz, CDCl3) δ8.08–8.05 (m, 4H), 7.99 (d, J = 8.0 Hz, 2H), 7.68–7.65 (m, 6H), 7.55 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 2.0 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.17–7.03 (m, 3H); 13C NMR (100 MHz, CDCl3) δ164.43, 164.13, 161.46, 151.48, 150.55, 139.84, 134.61, 132.41, 132.10, 132.01, 131.95, 131.70, 129.90, 129.18, 128.08, 127.82, 127.20, 122.01, 117.25, 114.63; HRMS (ESI) (m/z): calcd for C35H21Br3O6[M+NH4]+793.9206, found 793.9171.
Data for (E)-5-(4-((4-nitrobenzoyl)oxy)styryl)-1,3-phenylene bis(4-nitrobenzoate) (I-6). Pale yellow solid; yield 79%; mp 237–239 °C. 1H NMR (400 MHz, CDCl3) δ8.42–8.27 (m, 12H), 7.59 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 2.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 7.23–7.06 (m, 3H); 13C NMR (100 MHz, CDCl3) δ162.97, 151.28, 151.09, 150.39, 140.11, 134.79, 134.46, 131.40, 131.37, 130.95, 130.20, 128.86, 127.97, 127.15, 123.89, 123.80, 123.72, 121.91, 117.40, 114.37; HRMS (ESI) (m/z): calcd for C35H21N3O12 [M-OH]- 658.1092, found 657.9651.
Data for (E)-5-(4-((2-methylbenzoyl)oxy)styryl)-1,3-phenylene bis(2-methylbenzoate) (I-7). White solid; yield 81%; mp 192–193 °C. 1H NMR (400 MHz, CDCl3) δ8.21–8.15 (m, 3H), 7.57 (d, J = 8.4 Hz, 2H), 7.52–7.47 (m, 3H), 7.36–7.31 (m, 8H), 7.22 (d, J = 8.4 Hz, 2H), 7.15–7.05 (m, 3H), 2.70 (s, 6H), 2.68 (s, 3H); 13C NMR (100MHz, CDCl3) δ165.74, 165.38, 151.70, 150.68, 141.57, 141.43, 139.72, 134.54, 132.96, 132.83, 132.06, 132.01, 131.30, 131.21, 129.75, 128.18, 127.75, 127.29, 126.02, 125.96, 122.19, 117.26, 114.98, 22.07, 22.00; HRMS (ESI) (m/z): calcd for C38H30O6 [M+NH4]+ 600.2381, found 600.2379.
Data for (E)-5-(4-((3-methylbenzoyl)oxy)styryl)-1,3-phenylene bis(3-methylbenzoate) (I-8). White solid; yield 78%; mp 107–108 °C. 1H NMR (400 MHz, CDCl3) δ8.04–8.00 (m, 6H), 7.56 (d, J = 8.4 Hz, 2H), 7.47–7.38 (m, 6H), 7.32 (d, J = 2.0 Hz, 2H), 7.23 (t, J = 8.0 Hz, 2H), 7.18–7.04 (m, 3H), 2.46 (s, 6H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ165.27, 164.98, 151.77, 150.80, 139.72, 138.51, 138.46, 134.56, 134.44, 130.77, 130.72, 129.78, 129.41, 129.23, 128.55, 128.50, 127.75, 127.42, 127.37, 127.32, 122.08, 117.17, 114.80, 21.32; HRMS (ESI) (m/z): calcd for C38H30O6 [M+NH4]+ 600.2381, found 600.2379.
Data for (E)-5-(4-((2,4,6-trimethylbenzoyl)oxy)styryl)-1,3-phenylene bis(2,4,6-trimethylbenzoate) (I-9). White solid; yield 79%; mp 173–175 °C. 1H NMR (400 MHz, CDCl3) δ7.59 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 1.6 Hz, 2H), 7.27–7.24 (m, 2H), 7.17–7.06 (m, 3H), 6.95–6.91 (m, 6H), 2.48 (s, 12H), 2.46 (s, 6H), 2.33 (s, 6H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3) δ168.31, 167.88, 151.62, 150.56, 140.27, 140.09, 139.80, 135.93, 135.69, 134.62, 129.85, 129.51, 128.79, 128.70, 127.86, 127.33, 121.95, 117.04, 114.26, 21.23, 20.24, 20.07; HRMS (ESI) (m/z): calcd for C44H42O6 [M+NH4]+ 684.3320, found 684.3316.
Data for (E)-5-(4-((4-(tert-butyl)benzoyl)oxy)styryl)-1,3-phenylene bis(4-(tert-butyl)benzoate) (I-10). Pale yellow solid; yield 74%; mp 102–103 °C. 1H NMR (400 MHz, CDCl3) δ8.16–8.12 (m, 6H), 7.57–7.52 (m, 8H), 7.30 (d, J = 2.0 Hz, 2H), 7.21 (d, J = 8.6 Hz, 2H), 7.14–7.02 (m, 3H), 1.38 (s, 18H), 1.37 (s, 9H); 13C NMR (100MHz, CDCl3) δ165.11, 164.86, 157.62, 157.49, 151.78, 150.80, 139.66, 134.51, 130.18, 130.14, 129.74, 127.74, 127.30, 126.66, 126.47, 125.67, 125.61, 122.12, 117.19, 114.87, 35.25, 31.14; HRMS (ESI) (m/z): calcd for C47H48O6 [M+NH4]+ 726.3789, found 726.4049.
Data for (E)-5-(4-((cyclopropanecarbonyl)oxy)styryl)-1,3-phenylene dicyclopropanecarboxylate (II-1). Yellow solid; yield 71%; mp 136–138 °C. 1H NMR (400 MHz, CDCl3) δ7.47 (d, J = 8.4 Hz, 2H), 7.13–6.91 (m, 6H), 6.83 (t, J = 2.0 Hz, 1H), 1.89–1.79 (m, 3H), 1.22–1.14 (m, 6H), 1.07–0.99 (m, 6H); 13C NMR (100 MHz, CDCl3) δ173.44, 173.11, 151.40, 150.52, 139.42, 134.36, 129.55, 127.59, 127.19, 121.92, 116.82, 114.50, 13.04, 9.40, 9.35; HRMS (ESI) (m/z): calcd for C26H24O6 [M+NH4]+ 450.1911, found 450.1914.
Data for (E)-5-(4-((cyclohexanecarbonyl)oxy)styryl)-1,3-phenylene dicyclohexanecarboxylate (II-2). White solid; yield 72%; mp 131–133 °C. 1H NMR (400 MHz, CDCl3) δ7.47 (d, J = 8.4 Hz, 2H), 7.08 (.m, J = 1.6 Hz, 3H), 7.04 (d, J = 5.12 Hz, 2H), 7.00–6.91 (m, 1H), 6.82–6.72 (m, 1H), 2.60–2.50 (m, 3H), 2.12–2.02 (m, 6H), 1.87–1.78 (m, 6H), 1.71–1.68 (m, 2H), 1.65–1.55 (m, 6H), 1.43–1.24 (m, 10H); 13C NMR (100 MHz, CDCl3) δ174.47, 174.11, 151.56, 150.65, 139.44, 134.34, 129.55, 127.58, 127.20, 121.88, 116.73, 114.42, 43.22, 28.94, 25.72, 25.36; HRMS (ESI) (m/z): calcd for C35H42O6 [M+NH4]+ 576.3320, found 576.3323.
Data for 5-((E)-4-(cinnamoyloxy)styryl)-1,3-phenylene (2E,2'E)-bis(3-phenylacrylate) (II-3). Yellow solid; yield 83%; mp 87–89 °C. 1H NMR (400 MHz, CDCl3) δ7.93–7.86 (m, 3H), 7.62–7.57 (m, 6H), 7.53 (d, J = 8.6 Hz, 2H), 7.46–7.38 (m, 10H), 7.25 (d, J = 2.3 Hz, 2H), 7.18 (d, J = 8.6 Hz, 2H), 7.15–6.98 (m, 3H), 6.67–6.61 (m, 3H); 13C NMR (100 MHz, CDCl3) δ165.36, 165.04, 151.52, 150.57, 147.07, 146.80, 139.62, 134.51, 134.16, 134.11, 130.86, 130.79, 129.70, 129.06, 128.98, 128.41, 128.36, 127.73, 127.30, 121.98, 117.19, 117.01, 114.58; HRMS (ESI) (m/z): calcd for C41H30O6 [M+NH4]+ 636.2381, found 636.2383.
Data for (E)-5-(4-(propionyloxy)styryl)-1,3-phenylene dipropionate (II-4). Brown solid; yield 89%; mp 56–58 °C. 1H NMR (400 MHz, CDCl3) δ7.48 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 2.0 Hz, 2H), 7.10–7.07 (m, 2H), 7.05–6.92 (m, 2H), 6.82 (t, J = 2.0 Hz, 1H), 2.63–2.56 (m, 6H), 1.27 (t, J = 7.6 Hz, 9H); 13C NMR (100 MHz, CDCl3) δ172.92, 172.57, 151.41, 150.52, 139.50, 134.39, 129.60, 127.63, 127.20, 121.89, 116.82, 114.41, 27.78, 9.08, 9.05; HRMS (ESI) (m/z): calcd for C23H24O6 [M+NH4]+ 414.1911, found 414.1910.
Data for (E)-5-(4-(acryloyloxy)styryl)-1,3-phenylene diacrylate (II-5). White solid; yield 65%; mp 186–188 °C. 1H NMR (400 MHz, CDCl3) δ7.48 (d, J = 8.5 Hz, 2H), 7.13–7.11 (m, 2H), 7.10–7.07 (m, 2H), 7.05–6.93 (m, 2H), 6.84–6.81 (m, 1H), 2.31 (s, 9H); 13C NMR (100 MHz, CDCl3) δ169.45, 169.04, 151.32, 150.44, 139.55, 134.48, 129.67, 127.68, 127.20, 121.91, 116.93, 114.42, 21.14; HRMS (ESI) (m/z): calcd for C23H18O6 [M-H2O]+ 372.0997, found 372.1443.
Data for (E)-5-(4-(nicotinoyloxy)styryl)-1,3-phenylene dinicotinate (III-1). Yellow solid; yield 71%; mp 135–137 °C. 1H NMR (400 MHz, CDCl3) δ9.45–9.39 (m, 3H), 8.92–8.85 (m, 3H), 8.51–8.44 (m, 3H), 7.58 (d, J = 8.4 Hz, 1H), 7.54–7.47 (m, 4H), 7.37 (d, J = 1.6 Hz, 1H), 7.25–7.20 (m, 2H), 7.17–7.14 (m, 1H), 7.12–6.92 (m, 3H); 13C NMR (100 MHz, CDCl3) δ163.79, 163.49, 154.18, 151.36, 151.26, 137.77, 134.74, 130.08, 127.91, 127.76, 127.19, 125.33, 123.65, 123.60, 121.96, 121.85, 117.37; HRMS (ESI) (m/z): calcd for C32H21N3O6 [M+H]+ 544.1503, found 544.1505.
Data for (E)-5-(4-((thiophene-2-carbonyl)oxy)styryl)-1,3-phenylene bis(thiophene-3-carboxylate) (III-2). Brown solid; yield 70 %; mp 138–140 °C. 1H NMR (400 MHz, CDCl3) δ8.34–8.29 (m, 3H), 7.69–7.65 (m, 3H), 7.53 (d, J = 8.6 Hz, 2H), 7.40–7.36 (m, 3H), 7.29 (d, J = 2.0 Hz, 2H), 7.20 (d, J = 8.6 Hz, 2H), 7.16–7.01 (m, 3H); 13C NMR (100 MHz, CDCl3) δ160.96, 160.65, 151.42, 150.47, 139.70, 134.54, 134.35, 134.17, 132.78, 132.56, 129.77, 128.24, 127.76, 127.26, 126.55, 126.45, 122.06, 117.19, 114.74; HRMS (ESI) (m/z): calcd for C29H18O6S3 [M+NH4]+ 576.0604, found 576.0605.
Data for (E)-5-(4-((thiophene-2-carbonyl)oxy)styryl)-1,3-phenylene bis(thiophene-2-carboxylate) (III-3). Yellow solid; yield 78 %; mp 113–115°C. 1H NMR (400 MHz, CDCl3) δ8.03–7.96 (m, 3H), 7.71–7.65 (m, 3H), 7.54 (d, J = 8.3 Hz, 2H), 7.34–7.29 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.20–7.16 (m, 3H), 7.13–7.01 (m, 3H); 13C NMR (100 MHz, CDCl3) δ160.50, 160.19, 151.27, 150.37, 139.70, 134.99, 134.81, 134.61, 133.88, 133.64, 132.78, 132.52, 129.84, 128.15, 128.09, 127.76, 127.25, 122.01, 117.22, 114.62; HRMS (ESI) (m/z): calcd for C29H18O6S3 [M+NH4]+ 576.0604, found 576.0605.
Data for (E)-5-(4-((furan-2-carbonyl)oxy)styryl)-1,3-phenylene bis(furan-2-carboxylate) (III-4). Brown solid; yield 85%; mp 144–146°C. 1H NMR (400 MHz, CDCl3) δ7.73–7.66 (m, 3H), 7.53 (d, J = 7.9 Hz, 2H), 7.43–7.37 (m, 3H), 7.32–7.28 (m, 2H), 7.22 (d, J = 8.1 Hz, 2H), 7.15–6.98 (m, 3H), 6.64–6.56 (m, 3H); 13C NMR (100 MHz, CDCl3) δ156.83, 156.46, 150.92, 149.99, 147.46, 147.27, 143.89, 143.68, 139.76, 134.65, 129.88, 127.81, 127.23, 121.95, 119.87, 119.63, 117.21, 114.48, 112.32, 112.26; HRMS (ESI) (m/z): calcd for C29H18O9 [M+NH4]+ 528.1289, found 528.1291.
2.3 Biological assay
Each bioassay was repeated three times at 25±1°C. The activity results were estimated according to a percentage scale of 0−100 (0 indicating no activity and 100 indicating total mortality). The bioassay procedures for the anti-TMV, fungicidal, and insecticidal activities of the synthesized compounds are described in detailed in our published literature and can also be found in the Supporting Information30.