2.3. General Experimental Procedure
2.3.1. Synthesis of Methyl 4, 6-O-Benzylidene-α-D-Glucopyranoside (13)
Methyl α-D-glucopyranoside 8 (10 g, 51.5 mmol) was dissolved in anhydrous N,N-dimethylformamide (100 mL) under a N2 atmosphere, p-toluene sulfonic acid (1.62 g, 9.4 mmol) was added, followed by the addition of benzaldehyde dimethyl acetal (9.2 mL, 61.8 mmol), and the solution was stirred under N2 for 16 h. After completion of the reaction, triethylamine (4 mL) was added to the reaction, which was then diluted with ethyl acetate. The organic layer was subsequently washed with saturated sodium bicarbonate and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (methanol/dichloromethane = 30:1) to yield product 13 (12 g, 93%) as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.49–7.47 (m, Ph, 2H), 7.36–7.34 (m, Ph, 3H), 5.49 (s, 1H), 4.70 (d, J = 3.9 Hz, 1H), 4.25 (dd, J = 6, 6 Hz, 1H), 3.87 (t, J = 9 Hz, 1H), 3.76–3.74 (m, 1H), 3.69 (t, J = 12, 1H), 3.57–3.53 (m, 2H), 3.43 (t, J = 12 Hz, 1H), 3.39 (s, 3H), 2.93 (d, J = 6 Hz, 1H); 13C NMR (151 MHz, CDCl3) δ 137.0, 129.2, 128.3, 126.4, 101.9, 99.9, 80.9, 72.7, 71.4, 68.9, 62.3, 55.5; HRMS (ESI): mass calcd for C14H18O6 [M + H]+, 283.1176; found, 283.1168.
2.3.2. Synthesis of Methyl 2,3-di-O-Benzyl-4,6-O-Benzylidene-α-D-Glucopyranoside (14)
Methyl 4,6-O-benzylidene-α-D-glucopyranoside 13 (11.5 g, 40.73 mmol) was dissolved in anhydrous N,N-dimethylformamide (100 mL) under a N2 atmosphere. The solution was cooled to 0 °C in an ice bath, after which NaH (60% dispersion in mineral oil, 4 g, 163 mmol) was added, and the reaction was stirred for 1 h at room temperature. The solution was cooled to 0 °C, and benzylbromide (14.5 mL, 122 mmol) was added dropwise. The solution was stirred at room temperature overnight, after which methanol (10 mL) was added, and the mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 (200 mL), washed with water (2 × 75 mL) and brine (1 × 75 mL), and dried over MgSO4. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:7) to yield product 14 (17.5 g, 92%) as a white solid compound. 1H NMR (600 MHz, CDCl3) δ 7.49 (d, J = 6, 2H), 7.39–7.21 (m, 13H), 5.54 (s, 1H), 4.91 (d, J = 12 Hz, 1H), 4.84 (dd, J = 12 Hz, 2H), 4.70 (d, J = 12 Hz, 1H), 4.60 (d, J = 6 Hz, 1H), 4.26 (dd, J = 12, 6 Hz, 1H), 4.05 (t, J = 9 Hz, 1H), 3.84–3.80 (m, 1H), 3.70 (t, J = 9 Hz, 1H), 3.60 (t, J = 9Hz, 1H), 3.55 (dd, J = 3 Hz, 1H), 3.39 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 138.8, 138.2, 137.5, 129.0, 128.5, 128.4, 128.3, 128.2, 128.1, 128, 127.7, 126.1, 101.3, 99.3, 82.2, 79.2, 78.6, 75.4, 73.8, 69.1, 62.4, 55.4; HRMS (ESI): mass calcd for C28H30O6 [M + H]+, 463.2115; found, 463.2112.
2.3.3. Synthesis of Methyl 2,3,6-tri-O-Benzyl-α-D-Glucopyranoside (15)
Methyl 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside 14 (17.25 g, 38 mmol) was dissolved in anhydrous CH2Cl2 (100 mL) under a N2 atmosphere, and the solution was cooled to 0 °C. Et3SiH (30 mL, 186 mmol) and trifluoroacetic acid (14 mL, 186 mmol) were added, and the solution was stirred at 0 °C for 4 h. The reaction was quenched with Et3N and methanol. CH2Cl2 was added, and the solution was washed with water and brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The mixture was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:4) to afford product 15 (12 g, 91%) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ 7.37–7.26 (m, 15H), 5 (d, J = 12 Hz, 1H), 4.76 (dd, J = 12 Hz, 2H), 4.76–4.63 (m, 2H), 4.59 (d, J = 12 Hz, 1H), 4.54 (d, J = 12, 1H), 3.79 (t, J = 12, 18 Hz, 1H), 3.71–3.68 (m, 3H), 3.61 (t, J = 12, 18 Hz, 1H), 3.54 (dd, J = 6 Hz, 1H), 3.38 (s, 3H), 2.33 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 138.8, 138.1, 138.0, 128.6, 128.5, 128.4, 128.1, 128.0, 128.0, 127.9, 127.7, 127.6, 98.2, 81.5, 79.6, 77.2, 77.0, 76.8, 75.4, 73.6, 73.2, 70.7, 69.9, 69.5, 55.3; HRMS (ESI): mass calcd for C28H32O6 [M + NH4]+, 482.2537; found, 487.2525.
2.3.4. Synthesis of Methyl 2,3,6-Tri-O-Benzyloxy-4-O-Methyl-α-D-Glucopyranoside (16)
NaH (60% dispersion in mineral oil, 1.5 g, 63 mmol) was added to a solution of methyl 2,3,6-tri-O-benzyloxy-α-D-glucopyranoside 15 (11.5 g, 25 mmol) in anhydrous N,N- dimethylformamide (100 mL) at 0 °C. The reaction mixture was stirred for 1 h at 0 °C, and methyl iodide (3.8 mL, 63 mmol) was added to the reaction mixture. The reaction mixture was stirred overnight at room temperature. The reaction was quenched with methanol and ice-cold water and then extracted with ethyl acetate. The collected organic layers were washed with brine, dried with Na2SO4, and concentrated under reduced pressure. The mixture was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:7) to yield product 16 (11.2 g, 95%) as a viscous liquid. 1H NMR (600 MHz, CDCl3) δ 7.39–7.26 (m, 5H), 4.93 (d, J = 10.8, 1H), 4.83–4.74 (m, 2H), 4.67–4.57 (m, 3H), 4.51 (d, J = 12.1 Hz, 1H), 3.86 (s, 1H), 3.66 (dd, J = 22.7, 7.1 Hz, 3H), 3.50 (dd, J = 9.7, 3.5 Hz, 1H), 3.46 (s, 3H), 3.37 (s, 3H), 3.33 (s, 1H); 13C NMR (151 MHz, CDCl3) δ 138.9, 138.2, 138.0, 128.4, 128.4, 128.3, 128.1, 128.0, 127.9, 127.8, 127.6, 127.6, 98.2, 82.1, 79.6, 79.4, 75.7, 73.5, 73.4, 70.1, 68.6, 60.7, 55.2; HRMS (ESI): mass calcd for C29H34O6 [M + NH4]+, 496.2694; found, 496.2688.
2.3.5. Synthesis of Methyl 4-O-Methyl-α-D-Glucopyranoside (17)
Pd (10%)/C (3 g) was added to a solution of methyl 2,3,6-Tri-O-benzyloxy-4-O-methyl-α-D-glucopyranoside 16 (11 g, 22 mmol) in anhydrous methanol (100 mL), and the mixture was stirred under an atmosphere of hydrogen at room temperature for 24 h. The catalyst was filtered out, and the solvents were removed under reduced pressure. The crude residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:1) to afford the viscous product 17 (4.6 g, 95%). 1H NMR (600 MHz, CD3OD) δ 4.69 (s, 1H), 3.78 (d, J = 11.7 Hz, 1H), 3.70 (dq, J = 12.2, 6.9, 4.4 Hz, 2H), 3.57 (s, 3H), 3.53–3.47 (m, 1H), 3.44 (d, J = 7.9 Hz, 1H), 3.40 (s, 3H), 3.10 (t, J = 9.3 Hz, 1H); 13C NMR (151 MHz, CD3OD) δ 99.7, 79.6, 73.7, 72.1, 71.2, 60.8, 59.5, 54.2; HRMS (ESI): mass calcd for C8H16O6 [M + H]+, 209.1020; found, 209.1033.
2.3.6. Synthesis of Methyl 2,3,6-tri-O-Acetyl-α-D-Glucopyranoside (18)
Compound 17 (4.5 g, 22 mmol) was dissolved in acetic anhydride (25 mL, 217 mmol) and pyridine (25 mL, 217 mmol) and stirred at room temperature for 12 h. After completion of the reaction, pyridine and acetic anhydride were removed in vacuo. The residue was dissolved in CH2Cl2 and washed with dilute HCl. The organic layer was collected, washed with brine, dried with MgSO4, and concentrated under reduced pressure. The mixture was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:4) to afford the viscous product 18 (5.1 g, 71%). 1H NMR (600 MHz, CDCl3) δ 5.50–5.42 (m, 1H), 4.88–4.79 (m, 2H), 4.35 (d, J = 10.0 Hz, 1H), 4.30–4.24 (m, 1H), 3.88–3.81 (m, 1H), 3.42 (d, J = 3.7 Hz, 3H), 3.39 (d, J = 3.9 Hz, 3H), 3.34 (dd, J = 12.6, 6.3 Hz, 1H), 2.12 (d, J = 3.9 Hz, 3H), 2.08 (d, J = 6.0 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 170.7, 170.4, 169.8, 96.8, 77.8, 71.9, 71.1, 68.2, 62.7, 60.1, 55.3, 20.9, 20.8, 20.8; HRMS (ESI): mass calcd for C14H22O9 [M + NH4]+, 352.1602; found, 352.1605.
2.3.7. Synthesis of 1,2,3,6-Tetra-O-Acetyl-4-O-Methyl-α-D-Glucopyranoside (19)
To a stirred solution of 18 (5 g, 15 mmol) in acetic anhydride (50 mL) at 0 °C, boron trifluoride ether (2 mL, 15 mmol) was added. The solution was warmed to room temperature and allowed to stir for 2 h. Then, the solution was poured into an ice-cold saturated solution of NaHCO3 and extracted with ethyl acetate. The combined organic layers were separated, dried over MgSO4, and concentrated under reduced pressure. The mixture was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:2) to yield the viscous product 19 (4.1 g, 75%). 1H NMR (600 MHz, CDCl3) δ 6.25 (t, J = 3.1 Hz, 1H), 5.45 (ddd, J = 10.2, 9.2, 2.4 Hz, 1H), 5.0 (ddd, J = 10.3, 3.7, 2.7 Hz, 1H), 4.35–4.31 (m, 1H), 4.28–4.24 (m, 1H), 3.99–3.92 (m, 1H), 3.45 (d, J = 2.3 Hz, 3H), 3.43 (d, J = 2.2 Hz, 1H), 2.16 (d, J = 2.3 Hz, 3H), 2.12–2.09 (m, 6H), 2.01 (d, J = 2.4 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 170.6, 170.0, 169.9, 169.0, 89.2, 71.7, 71.0, 69.6, 62.3, 60.5, 20.9, 20.8, 20.5; HRMS (ESI): mass calcd for C15H22O10 [M + NH4]+, 380.1551; found, 380.1545.
2.3.8. Synthesis of 2,3,6-O-Triacetyl-4-O-Methylglucopyranosyl bromide (6)
A solution of HBr (10 mL, 33 wt% in acetic acid) was added dropwise to a stirred solution of compound 19 (3.7 g, 10 mmol) in CH2Cl2 (50 mL) at 0 °C. The solution was stirred at room temperature for 4 h. After completion of the reaction, the reaction mixture was quenched carefully with ice water and diluted with CH2Cl2 and water. The organic layer was separated and washed with saturated NaHCO3 and brine. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethylacetate/n-hexane 1:4) to yield the light yellow liquid 6 (2.8 g, 73%). This compound was unstable, and after drying, it was used for further reactions. 1H NMR (600 MHz, CDCl3) δ 6.53 (d, 1H, J = 3.7 Hz), 5.57 (t, J = 9.6 Hz, 1H), 4.75 (dd, J = 10.0, 3.8 Hz, 1H), 4.39 (d, J = 12.4 Hz, 1H), 4.31 (dd, J = 12.4, 4.0 Hz, 1H), 4.15 (d, J = 10.1 Hz, 1H), 3.45 (d, J = 9.7 Hz, 4H), 2.12 (d, J = 6.6 Hz, 6H), 2.10 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 170.5, 170.1, 169.6, 86.8, 76.6, 73.2, 71.8, 70.9, 61.8, 60.3, 20.9, 20.8, 20.7.
2.3.9. Synthesis of 3,5-bis(tert-Butyldimethylsilyloxy) Benzaldehyde (20)
To a well-stirred solution of 3,5-dihydroxybenzaldehyde 9 (2 g, 14.48 mmol) and DIPEA (5.3 mL, 43.4 mmol) in N,N- dimethylformamide (20 mL), tert-butylchlorodimethylsilane (6.55 g, 43.4 mmol) was added at 0 °C, and the reaction mixture was stirred for 3 h at room temperature. The reaction mixture was diluted with CH2Cl2 and washed with saturated aqueous NaCl, and the combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:20) to afford 20 (5.1 g, 96%) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ 9.9 (s, 1H), 7.0 (s, 2H), 6.6 (s, 1H), 1.0 (s, 18H), 0.2 (s, 12H); 13C NMR (151 MHz, CDCl3) δ 191.9, 157.3, 138.3, 118.4, 114.4, 25.7, 25.6, 18.2; HRMS (ESI): mass calcd for C19H34O3Si2[M + H]+, 367.2119; found, 367.2113.
2.3.10. Synthesis of (5-Vinyl-1,3-Phenylene)bis(oxy)bis(tert-Butyldimethylsilane (21)
A mixture of methyltriphenylphosphonium bromide (7.3 g, 20.4 mmol) and potassium tert-butoxide (2.2 g, 20 mmol) in anhydrous THF was refluxed for 1 h for in situ generation of methylenetriphenylphosphorane. Upon returning to room temperature, a solution of 3,5-di(tert-butyldimethylsilyloxy) benzaldehyde 20 (5 g, 13.6 mmol) in anhydrous THF was added dropwise, and the reaction was heated to reflux overnight. After completion of the reaction, ethyl acetate was added, and the solution was washed with water, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:25) to yield product 21 (3.4 g, 68%) as a colorless oil. 1H NMR (600 MHz, CDCl3) δ 6.6 (dd, J = 17.4, 10.9 Hz, 1H), 6.5 (s, 2H), 6.3 (s, 1H), 5.7 (d, J = 17.5 Hz, 1H), 5.2 (d, J = 10.9 Hz, 1H), 1.0 (s, 18H), 0.2 (s, 12H); 13C NMR (151 MHz, CDCl3) δ 156.6, 139.4, 136.7, 113.9, 111.7, 111.5, 25.7, 25.7, 18.2; HRMS (ESI): mass calcd for C20H36O2Si2[M + H]+, 365.2327; found, 365.2333.
2.3.11. Synthesis of 5-Vinylbenzene-1,3-diol, [3,5-Dihdroxy Styrene] (12)
To a solution of (5-vinyl-1,3-phenylene) bis(oxy)bis(tert-butyldimethylsilane) 21 (3 g, 8.2 mmol) in anhydrous THF (15 mL), TBAF (4 mL, 14 mmol) was added at 0 °C, and the reaction mixture was stirred for 3 h at room temperature. The volume was reduced by rotary evaporation, and ethyl acetate was added. The organic layer was washed with water, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:1) to yield product 12 (1.2 g, 92%) as a viscous pale oil. 1H NMR (600 MHz, CD3OD) δ 6.6 (dd, J = 17.4, 11.0 Hz, 1H), 6.4 (s, 2H), 6.2 (s, 1H), 5.6 (d, J = 17.6 Hz, 1H), 5.1 (d, J = 10.8 Hz, 1H); 13C NMR (151 MHz, CD3OD) δ 158.2, 139.6, 137.0, 112.3, 104.4, 101.8, 35.6, 35.2; HRMS (ESI): mass calcd for C8H8O2[M + H]+, 137.0597; found, 137.0621.
2.3.12. Synthesis of 5-Vinyl-1,3-Phenylene Diacetate (3,5-Diacetoxystyrene) (5)
Acetic anhydride (2 mL, 22 mmol) was added dropwise to a solution of compound 12 (1 g, 7.3 mmol), pyridine (1.9 mL, 22 mmol), and DMAP (26 mg, 0.219 mmol) in CH2Cl2 at 0 °C. The reaction mixture was stirred at room temperature for 12 h. The solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:4) to yield 5-vinyl-1,3-phenylene diacetate 5 (1.12 g, 70%) as a clear oil. 1H NMR (600 MHz, CDCl3) δ 7.0 (s, 2H), 6.8 (s, 1H), 6.6 (dd, 1H, J = 17.1, 11.2 Hz), 5.7 (d, 1H, J = 17.5 Hz), 5.3 (d, 1H, J = 10.8 Hz), 2.3 (s, 6H); 13C NMR (151 MHz, CDCl3) δ 169.0, 151.2, 139.9, 135.3, 116.7, 115.9, 114.7, 21.0; HRMS (ESI): mass calcd for C12H12O4[M + NH4]+, 238.1074; found, 238.1085.
2.3.13. Synthesis of 4-Iodophyenyl Acetate (11)
To a well-stirred mixture of 4- iodophenol 7 (2 g, 9 mmol) in dry pyridine (6 mL), acetic anhydride (1.75 mL, 18 mmol) was added at room temperature under N2. The mixture was then stirred for 12 h. After completion of the reaction, water was added and extracted with CH2Cl2. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (dichloromethane 100%) to yield product 11 (2.2 g, 95%) as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.7–7.6 (m, 2H), 6.9–6.8 (m, 2H), 2.3 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 169.1, 150.5, 138.5, 123.8, 89.9, 21.1; HRMS (ESI): mass calcd for C8H7 IO2[M + NH4]+, 279.9827; found, 279.9826.
2.3.14. Synthesis of 4-Iodophenyl-2′,3′,6′-O-triacetyl-4′-O-Methylglucopyranoside (4)
To a mixture of iodophenol 7 (259 mg, 1.9 mmol) and 2,3,6-O-triacetyl-4-methylglucopyranosyl bromide 6 (730 mg, 1.9 mmol) in CHCl3, benzyltributylammonium chloride (60 mg, 0.19 mmol) and potassium carbonate (665 mg, 4.8 mmol) were added and stirred at room temperature for 24 h. The reaction mixture was neutralized with 1 N HCl, and the organic layer was separated. The organic layer was washed with water-saturated NaHCO3 and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:4) to yield product 4 (565 mg, 57%) as a white solid. 1H NMR (600 MHz, CDCl3) δ 7.56–7.54 (m, 2H), 6.74 (dd, J = 8.9, 2.7 Hz 2H), 5.22 (t, J = 9.3 Hz, 1H), 5.12 (dd, J = 9.6, 7.7 Hz, 1H), 4.98 (d, J = 7.8 Hz, 1H), 4.38 (dd, J = 12.0, 2.4 Hz, 1H), 4.24 (dd, J = 12.1, 5.6 Hz, 1H), 3.67 (ddd, J = 10.1, 5.7, 2.4 Hz, 1H), 3.43 (d, J = 2.5 Hz, 4H), 2.08 (d, J = 8.5 Hz, 6H), 2.03 (d, J = 2.5 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 170.5, 170.0, 169.6, 156.7, 138.4, 119.2, 98.7, 86.0, 77.5, 74.7, 73.1, 71.5, 62.7, 60.5, 20.9, 20.8, 20.7; HRMS (ESI): mass calcd for C19H23IO9[M + NH4]+, 540.0725; found, 540.0712.
2.3.15. Synthesis of (E)-1″-(3,5-Diacetoxy)-2″-(4′-O-2‴,3‴,6‴-Triacetyl-4‴-O-Methyl-β-D Glucopyranosidophenyl) Ethene (22)
To a solution of 3,5-diacetoxystyrene 5 (235 mg, 1.07 mmol) and compound 4 (560 mg, 1.07 mmol) in acetonitrile, palladium(II) acetate (0.012 mg, 0.053 mmol), benzyltriethylammonium chloride (243 mg,1.07 mmol), and tributylamine (0.68 mL, 2.9 mmol) were added and stirred at 100 °C for 2 h, N2. After 2 h, the mixture was cooled to room temperature, filtered through a short Celite pad, and then evaporated to dryness. The residue was taken up in dichloromethane, washed with diluted HCl, water, and brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:2) to yield compound 22 (361 mg, 55%) as a white crystal. 1H NMR (600 MHz, CDCl3) δ 7.41 (d, J = 8.5 Hz, 2H), 7.10 (s, 2H), 7.02 (d, J = 16.2 Hz, 1H), 6.97 (d, J = 8.5 Hz, 2H), 6.91 (d, J = 16.2 Hz, 1H), 6.80 (s, 1H), 5.26 (t, J = 9.3 Hz, 1H), 5.17 (t, J = 8.7 Hz, 1H), 5.07 (d, J = 7.8 Hz, 1H), 4.42 (d, J = 11.9 Hz, 1H), 4.29 (dd, J = 11.9, 5.4 Hz, 1H), 3.74–3.68 (m, 1H), 3.46 (s, 4H), 2.30 (s, 6H), 2.11 (d, J = 5.5 Hz, 6H), 2.06 (s, 3H). 13C NMR (151 MHz, CDCl3) δ 170.6, 170.1, 169.7, 169.0, 156.8, 151.3, 139.7, 131.9, 129.7, 127.9, 126.0, 117.1, 116.8, 114.2, 98.7, 77.6, 74.8, 73.1, 71.6, 62.7, 60.5, 21.1, 20.9, 20.8, 20.7; HRMS (ESI): mass calcd for C31H34O13[M + NH4] +, 632.2338; found, 632.2342.
2.3.16. Synthesis of 4′-O-β- (4‴-O-Methylglucopyranosyl)Resveratrol (2)
Compound 22 (350 mg, 0.58 mmol) was dissolved in methanol (20 mL) and 0.2 M methanolic solution of sodium methoxide (20 mL). The resulting mixture was stirred for 1 h at room temperature. After completion of the reaction, the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/dichloromethane = 1:8) to obtain the final compound 2 (195 mg, 85%) as a white powder. 1H NMR (600 MHz, (CD3)2CO) δ 8.23 (s, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.04 (d, J = 7.6 Hz, 3H), 6.97 (s, 1H), 6.56 (s, 2H), 6.28 (s, 1H), 4.96 (d, J = 7.7 Hz, 1H), 4.64 (s, 1H), 4.40 (d, J = 3.4 Hz, 1H), 3.84 (dd, J = 10.8, 4.5 Hz, 1H), 3.80–3.75 (m, 1H), 3.70 (dd, J = 11.7, 5.1 Hz, 1H), 3.63 (dd, J = 8.8, 3.3 Hz, 1H), 3.57 (s, 3H), 3.51–3.43 (m, 2H), 3.31 (d, J = 5.2 Hz, 1H), 3.22 (t, J = 9.3 Hz, 1H). 13C NMR (151 MHz, (CD3)2CO) δ 158.7, 157.5, 139.7, 131.5, 127.7, 127.5, 127.3, 116.6, 104.9, 102.0, 100.6, 79.2, 77.1, 76.1, 74.0, 61.2, 59.7; HRMS (ESI): mass calcd for C21H24O8[M + H]+, 405.1544; found, 405.1551.
2.3.17. Synthesis of 3-Hydroxy-5-Vinylphenyl-2′,3′,6′-tri-O-Acetyl-4′-O-Methyl-β-D-Glucopyranoside (10)
To a solution of dihydroxystyrene 12 (248 mg, 1.8 mmol) and 2,3,6-O-triacetyl-4 methylglucopyranosyl bromide 6 (700 mg, 1.8 mmol) in CHCl3, benzyltributylammonium chloride (56 mg, 0.18 mmol) and potassium carbonate (636 mg, 4.6 mmol) were added and stirred at room temperature for 24 h. The reaction mixture was neutralized with 1 N HCl, and the organic layer was separated. The organic layer was washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:2) to yield product 10 (320 mg, 40%) as a white product. 1H NMR (600 MHz, CDCl3) δ 6.59 (d, J = 17.1 Hz, 3H), 6.42 (s, 1H), 6.04 (s, 1H), 5.69 (d, J = 17.5 Hz, 1H), 5.25–5.23 (m, 2H), 5.13 (t, J = 8.6 Hz, 1H), 5.02 (d, J = 7.7 Hz, 1H), 4.42 (d, J = 11.8 Hz, 1H), 4.26 (dd, J = 11.7, 5.6 Hz, 1H), 3.71–3.69 (m, 1H), 3.45 (d, J = 12.0 Hz, 4H), 2.10 (d, J = 10.5 Hz, 6H), 2.05 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 170.3, 170.0, 158.1, 157.0, 140.0, 136.2, 114.9, 108.2, 107.1, 104.1, 98.7, 77.7, 74.8, 73.0, 71.7, 62.8, 60.5, 20.9, 20.8, 20.7; HRMS (ESI): mass calcd for C21H26O10[M + NH4]+, 456.1864; found, 456.1875.
2.3.18. Synthesis of 3-Acetoxy-5-Vinylphenyl-2′,3′,6′-tri-O-Acetyl-4′-O-Methyl-β-D-Glucopyranoside (23)
Compound 10 (310 mg, 0.7 mmol) in CH2Cl2 (5 mL) at room temperature was added to pyridine (0.1 mL, 1.06 mmol) and 4-dimethylaminopyridine (0.001 mg), and acetic anhydride (0.1 mL, 1.06 mmol) was added dropwise. The resulting mixture was stirred for 1 h. The mixture was diluted with CH2Cl2 and water. The organic phase was separated and washed with dilute hydrochloric acid, water, and brine, dried over anhydrous MgSO4, filtered, and dried under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:4) to yield product 23 (288 mg, 85%) as a white solid. 1H NMR (600 MHz, CDCl3) δ 6.86 (dd, J = 30.6, 2.0 Hz, 2H), 6.65–6.56 (m, 2H), 5.74–5.68 (m, 1H), 5.31–5.20 (m, 2H), 5.14 (ddt, J = 10.5, 7.8, 1.1 Hz, 1H), 5.05 (d, J = 7.7 Hz, 1H), 4.40 (dq, J = 12.0, 1.6 Hz, 1H), 4.27–4.20 (m, 1H), 3.75–3.68 (m, 1H), 3.47–3.39 (m, 5H), 2.27 (dd, J = 2.4, 1.1 Hz, 3H), 2.09 (dd, J = 2.3, 1.1 Hz, 3H), 2.07 (dd, J = 2.3, 1.1 Hz, 3H), 2.04 (dd, J = 2.3, 1.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 170.6, 170.0, 169.7, 169.1, 157.5, 151.5, 140.0, 135.6, 115.6, 114.2, 112.1, 109.8, 98.6, 77.7, 74.7, 73.1, 71.5, 62.9, 60.4, 21.1, 20.9, 20.7, 20.7; HRMS (ESI): mass calcd for C23H28O11[M + NH4]+, 498.1970; found, 498.1985.
2.3.19. Synthesis of (E)-1″-(3-Acetoxy-5-O-2‴,3‴,6‴-Triacetyl-4‴-O-Methyl-β-D Glucopyranosidophenyl)- 2″-(4′-Acetoxyphenyl) Ethene (24)
To a solution of 4-iodophenylacetate 11 (147 mg, 0.56 mmol), compound 23 (270 mg, 0.56 mmol) in acetonitrile was added with palladium(II) acetate (0.006 mg, 0.028 mmol), benzyltriethylammonium chloride (128 mg, 0.56 mmol), and tributylamine (0.36 mL, 1.5 mmol) and stirred at 100 °C for 2 h under nitrogen. After 2 h, the mixture was cooled to room temperature, filtered through a short Celite pad, and then evaporated to dryness. The residue was taken up in dichloromethane, washed with diluted hydrochloric acid, water, and brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/n-hexane = 1:2) to yield product 24 (275 mg, 80%) as a white crystal. 1H NMR (600 MHz, CDCl3) δ 7.5 (d, J = 8.0 Hz, 2H), 7.1–7.0 (m, 3H), 7.0–6.9 (m, 3H), 6.6 (s, 1H), 5.3 (t, J = 9.2 Hz, 1H), 5.2 (t, J = 8.5 Hz, 1H), 5.1 (d, J = 7.6 Hz, 1H), 4.4 (d, J = 11.9 Hz, 1H), 4.3 (dd, J = 11.4, 5.8 Hz, 1H), 3.7 (s, 1H), 3.5 (s, 4H), 2.3 (s, 6H), 2.1 (s, 3H), 2.1 (s, 6H); 13C NMR (151 MHz, CDCl3) δ 170.6, 170.1, 169.7, 169.0, 156.8, 151.3, 139.7, 131.9, 129.8, 127.9, 126.0, 117.1, 116.8, 114.2, 98.7, 77.6, 74.8, 73.1, 71.6, 62.7, 60.5, 21.1, 20.9, 20.8, 20.7; HRMS (ESI): mass calcd for C31H34O13[M + H]+, 637.1999; found, 637.2014.
2.3.20. Synthesis of 3-O-β-(4‴-O-Methylglucopyranosyl) Resveratrol (3)
Compound
24 (260 mg, 0.64 mmol) was dissolved in methanol (20 mL), and 0.2 M methanolic solution of sodium methoxide (20 mL) was added at room temperature. The resulting mixture was stirred for 1 h. The mixture was concentrated to dryness under reduced pressure. The residue was purified by silica gel column chromatography (methanol/dichloromethane = 1:8) to yield product
3 (217 mg, 84%) as a white powder.
1H NMR (600 MHz, (CD
3)
2CO) δ 7.36 (d,
J = 7.9 Hz, 2H), 7.03 (d,
J = 16.3 Hz, 1H), 6.85 (d,
J = 16.3 Hz, 1H), 6.79 (d,
J = 8.1 Hz, 2H), 6.72 (s, 1H), 6.64 (s, 1H), 6.41 (s, 1H), 4.86 (d,
J = 7.7 Hz, 1H), 3.81 (d,
J = 12.0 Hz, 1H), 3.65 (dd,
J = 12.0, 4.6 Hz, 1H), 3.59 (t,
J = 9.0 Hz, 1H), 3.52 (s, 3H), 3.46–3.37 (m, 2H), 3.16 (t,
J = 9.3 Hz, 1H);
13C NMR (151 MHz, (CD
3)
2CO) δ 159.3, 158.8, 157.7, 139.9, 128.7, 127.9, 125.4, 115.6, 107.3, 105.3, 102.9, 100.8, 79.2, 77.1, 76.1, 74.1, 61.2, 59.6; HRMS (ESI): mass calcd for C
21H
24O
8[M + NH
4]
+, 405.1544; found, 405.1551. The spectra of the above mentioned compounds is displayed in the part of
Supplemental Material.