3.4. synthesis of Triene Uruhsiol Hydroxyl Protection Compounds
Synthesis of
1,
2, and
3 [
14]: A solution of triene urushiol (0.3 mmol) and K
2CO
3 (1.2 mmol) and propargyl bromide (110 mg, 0.7 mmol) was dissolved in dry acetone (1 mL). The mixture was stirred at 30 °C for 24 h and quenched with H
2O (30 mL) in an ice bath. The solution was evaporated to remove acetone and extracted with CH
2Cl
2 (2 × 30 mL). The organic layer was washed with saturated NaHCO
3 and brine, dried over MgSO
4, filtered, and concentrated. The residue was purified by column chromatography with CHCl
3−MeOH (100:1) to afford compound
3. The synthesis methods of compounds
1 and
2 followed the path above.
Compound 1: yield 57%; brown oil; Rf = 0.90; 1H-NMR (400 MHz, CDCl3) δ 7.52 (-OH), 7.29 (s, 1H), 7.00 (s, 1H), 6.71 (s, 1H), 6.36 (t, J = 4.36 Hz, 1H), 6.00 (t, J = 4.06 Hz, 1H), 5.65 (t, J = 9.65 Hz, 1H), 5.46–5.37 (m, 5H), 3.52 (s, 1H), 2.61 (t, J = 3.98 Hz, 2H), 0.90 (t, J =2.65 Hz, 1H). 13C-NMR (101 MHz, CDCl3) δ 143.16, 142.09, 136.86, 132.34, 131.11, 129.97, 129.41, 126.83, 125.57, 124.34, 121.99, 120.01, 112.87, 58.77, 50.83, 27.18, 19.18, 14.12, 13.31. ESIMS m/z 167.0 [C5H13O2SSiH2]+.
Compound 2: yield 45%; brown oil; Rf = 0.91; 1H-NMR (400 MHz, CDCl3) δ 7.65 (m, 1H), 7.45 (m, 1H), 7.28 (s, 1H), 5.31–5.28 (d, J = 15.4 Hz, 2H), 1.18 (m, 8H). 13C-NMR (101 MHz, CDCl3) δ 167.70, 132.33, 13.71. ESIMS m/z 479.3 [C26H42O4SSi]+.
Compound 3: yield 67%; brown oil; Rf = 0.82; 1H-NMR (400 MHz, CDCl3) δ 7.52 (-OH), 7.00 (m, 1H), 6.79–6.77 (m, 3H), 6.35 (t, J = 4.16 Hz, 1H), 5.98 (t, J = 4.46 Hz, 1H), 5.64 (m, 1H), 5.44–5.35 (m, 3H), 4.73 (d, J = 2.3 Hz, 2H), 3.73 (d, J = 7.0 Hz, 1H). 13C-NMR (101 MHz, CDCl3) δ 150.44, 144.44, 143.90, 132.30, 131.10, 129.90, 129.39, 126.78, 125.55, 124.28, 123.40, 119.09, 110.16, 78.32, 76.73, 57.07, 30.62, 29.73, 29.71, 29.63, 29.49, 29.42, 29.25, 27.18. ESIMS m/z 352.3 [M-H]+.
Synthesis of compounds
4–
7 [
19]: A solution of triene urushiol (314 mg, 1 mmol) and phenylboronic acid (1.0 eq) was dissolved in DCM/EA (0.5 mL) and heated to 60 °C for 2 h in a pressure tube. After being concentrated in a vacuum, pure compound
4 (400 mg, 100%) was obtained. Repeat the step above to get compounds
5,
6, and
7, and their yields were 70–80%. The synthesis of compounds
14,
15, and
16 were also the same as the synthesis step of compound
4, and at r.t. for 2 h in a pressure tube.
Compound 4: yield 75%; brown oil; Rf = 0.75; 1H-NMR (400 MHz, CDCl3) δ 7.42 (d, J = 3.06 Hz, 1H), 7.34 (s, 1H), 7.17 (m, 1H), 7.04 (d, J = 2.80 Hz, 1H), 6.94 (t, J = 3.86 Hz, 1H), 6.87 (d, J = 2.85 Hz, 1H), 6.59 (s, 2H), 6.26 (t, J = 8.81 Hz, 1H), 6.15 (s, 2H), 5.89 (t, J = 2.65 Hz, 1H), 5.34–5.26 (m, 2H). 13C-NMR (101 MHz, CDCl3) δ 148.13, 146.81, 145.74, 132.30, 131.08, 131.06, 129.93, 129.41, 129.22, 127.90, 126.85, 125.57, 124.30, 123.18, 122.33, 121.40, 119.24, 114.70, 114.08, 13.29. ESIMS m/z 449.4 [C27H34BNO2]+.
Compound 5: yield 72%; brown oil; Rf = 0.74; 1H-NMR (400 MHz, CDCl3) δ 9.69 (s, 1H), 7.98 (s, 1H), 7.49 (s, 1H), 7.27, 7.20, 7.17, 6.97 (s, 6H), 5.27, 5.19, 3.39. 13C-NMR (101 MHz, CDCl3) δ 173.89, 173.44, 148.25, 148.18, 147.66, 130.74, 130.56, 130.26, 130.24, 129.43, 128.65, 128.47, 125.01, 124.55, 119.69, 34.63, 32.49, 30.29, 29.91, 27.75, 25.43, 24.44, 23.26, 14.67.ESIMS m/z 479.2 [M+C6H7]+.
Compound 6: yield 80%; brown oil; Rf = 0.70; 1H-NMR (400 MHz, CDCl3) δ 9.73 (s, 1H), 8.01 (s, 1H), 7.52 (d, J = 2.80 Hz, 1H), 7.33 (d, J = 1.88 Hz, 1H), 7.30 (d, J = 1.50 Hz, 1H), 7.23 (s, 1H), 7.10 (m, 1H), 7.00 (s, 1H), 5.30–5.23 (m, 6H), 4.25 (d, J = 8.78 Hz, 8H), 4.11 (m, 2H). 13C-NMR (101 MHz, CDCl3) δ 172.32, 171.87, 146.68, 146.61, 146.09, 129.17, 128.99, 128.69, 128.67, 127.85, 127.07, 126.90, 123.44, 122.97, 118.12, 33.05, 30.92, 28.72, 28.33, 26.18, 23.85, 22.87, 21.69, 13.09. ESIMS m/z 419.3 [M]+.
Compound 7: yield 70%; brown oil; Rf = 0.79; 1H-NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.96 (d, J = 0.80 Hz, 1H), 7.52 (m, 1H), 7.36 (t, J = 2.80 Hz, 1H), 6.70 (t, J = 5.80 Hz, 3H), 5.82(m, 1H), 5.3–5.34 (m, 3H), 4.97 (m, 1H), 1.61 (m, 5H), 1.33, 1.26. ESIMS m/z 448.1 [M + H]+.
Synthesis of compound
8 [
15]: Triene urushiol (1.0 mmol), K
2CO
3 (3.5 eq.) and 1,3-dibromopropane (1.3 eq.) were added to EtOH (1 mL) in turn, and then the mixture was heated at reflux for 5 h. The resulting mixture was washed with H
2O (5 mL) and organic layer was concentrated in vacuum to acquire the crude product, which was purified by column chromatography to afford the corresponding compound
8 with PE–EA (4:1,
v/
v) as eluents.
Compound 8: yield 70%; brown oil; Rf = 0.81; 1H-NMR (400 MHz, CDCl3) δ 6.83–6.75 (m, 3H), 6.34 (m, 1H), 6.00 (m, 1H), 5.63 (m, 1H), 5.40–5.35 (m, 3H), 4.18 (m, 2H), 3.58 (t, J = 1.80 Hz, 2H), 2.02, 1.74 (t, J = 1.10 Hz, 4H). 13C-NMR (101 MHz, CDCl3) δ 151.66, 149.70, 126.81, 126.78, 122.70, 122.68, 119.22, 119.20, 77.34, 70.48, 70.47, 27.23, 27.15, 14.10, 13.30. ESIMS m/z 405.1 [M]+.
Synthesis of compound
9 [
13]: To a solution of triene urushiol (1.0 mmol) in EA (1 mL) at 0 °C was added TEA (5.06 g, 50.0 mmol) and MsNH
2 (25 mg), successively. After the addition of MsNH
2, the mixture was vigorously stirred for 2 h. To the slurry was then added H
2O (10 mL). The two-phase mixture was separated. The organic layer was washed with H
2O (25 mL) and dried (MgSO
4). Removal of solvent under vacuum, the corresponding pure compound
9 was obtained.
Compound 9: yield 30%; brown oil; Rf = 0.80; 1H-NMR (400 MHz, CDCl3) δ 6.71–6.70 (t, J = 4.45 Hz, 3H), 6.34 (t, J = 4.80 Hz, 1H), 5.98 (t, J = 3.00 Hz, 1H), 5.63 (m, 1H), 5.42–5.35 (m, 3H), 3.71 (s, 3H). 13C-NMR (101 MHz, CDCl3) δ 143.08, 141.96, 132.31, 131.07, 129.39, 129.37, 126.83, 125.56, 124.33, 122.06, 120.06, 58.63, 13.30. ESIMS m/z 436.3 [M + 2Na]+.
Syntheses of Compound
10 [
16]: In a pressure tube (25 mL),
p-Toluene (1 eq.) was added into the mixture of triene urushiol (1 mmol) and ethyl acetoacetate (3 eq.), and the reaction mixture was vigorously stirred at ambient temperature for 8 h. The progress of reaction was monitored by TLC (eluent, PE:EA = 4:1). After the completion of the reaction, water (10.0 mL) was added into the reaction mixture. Evaporate the solvent to afford the pure compound
10 in excellent yields, and
10 was regarded as the reagent for compounds
12–
16.
Compound 10 (8-hydroxy-4-methyl-7-((8Z,11E,13Z)-pentadeca-8,11,13-trien-1-yl)-2H-chro men -2-one) yield 90%; Yellow liquid; Rf = 0.83; 1H-NMR (400 MHz, CDCl3) δ 6.88–6.48 (m, 5H), 6.49(d, J = 5.60 Hz, 1H), 6.22 (s, 1H), 6.02–5.88 (m, 3H), 2.94 (m, 2H), 2.68 (s, 2H),2.43(t, J = 0.98 Hz, 4H), 2.11(d, J = 7.01 Hz, 2H), 1.94(m, 2H), 1.50 (m, 2H), 1.36 (m, 2H), 1.27 (m, 3H). 13C-NMR (101 MHz, CDCl3) δ 167.46, 165.57, 164.44, 161.42, 155.03, 143.34, 142.18, 124.42, 122.44, 120.20, 119.95, 112.86, 112.07, 110.26, 106.90, 50.10, 30.13, 28.45, 28.28, 27.07, 25.15, 21.19, 19.51, 15.53, 14.11, 14.04. ESIMS m/z 448.4 [M + SiC3H9]+.
Syntheses of Compound 11: The purified triene urushiol (0.3 mmol) was etherified with methyl iodide (0.6 mmol) in MeCN (1 mL) and the crude product was concentrated under vacuum. The crude product was recrystallized in methanol (saturated urushiol dimethyl ether was not recrystallized) to give pure target compound 11.
Compound 11: yield 70%; Yellow liquid; Rf = 0.81; 1H-NMR (400 MHz, CDCl3) δ 6.94–6.65 (m, 3H), 6.34 (t, J = 4.08 Hz, 1H), 5.97 (t, J = 4.99 Hz, 1H), 5.61–5.35 (m, 3H), 3.93 (s, 3H), 3.79 (s, 3H). ESIMS m/z 341.0 [M − H]+.
Compound 12: yield 62%; Yellow liquid; Rf = 0.70; 1H-NMR (400 MHz, CDCl3) δ 6.73 (m, 1H), 6.71 (s, 1H), 6.67 (m, 1H), 6.23 (s, 1H), 5.98 (s, 1H), 5.89 (s, 1H), 2.39 (t, J = 9.80 Hz, 3H), 2.25 (m, 3H), 1.83 (s, 3H). 13C-NMR (101 MHz, CDCl3) δ 167.30, 161.19, 154.82, 112.88, 21.21, 19.53. ESIMS m/z 421.3 [M − H]+.
Compound 13: yield 66%; Yellow liquid; Rf = 0.50; 1H-NMR (400 MHz, CDCl3) δ 7.51 (s, 1H), 7.13 (s, 1H), 6.70 (s, 1H), 6.03 (d, J = 21.1 Hz, 1H), 5.44–5.17 (m, 6H), 4.64 (s, 2H), 3.40 (s, 1H), 2.60(t, J = 1.11 Hz, 2H), 2.40 (m, 2H), 2.24 (s, 3H), 2.05 (d, 3H),1.73 (d, 2H),1.60 (m, 2H),1.33 (m, 2H), 1.26(m, 2H), 0.88 (m, 2H). 13C-NMR (101 MHz, CDCl3) δ 171.43, 143.17, 142.05, 132.34, 131.04, 130.02, 129.92, 129.40, 129.37, 126.84, 124.36, 121.99, 120.01, 112.85, 61.77, 60.52, 50.89, 31.98, 31.81, 30.64, 29.79, 29.52, 27.23, 22.68, 21.08, 14.20, 13.32. ESIMS m/z 432.4 [M + H]+.
Compound 14: yield 28%; Yellow liquid; Rf = 0.90; 1H-NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.5 Hz, 1H), 7.52–7.05 (m, 3H), 6.16 (m, 1H), 5.90 (m, 1H), 5.72 (m, 1H), 5.69–5.64 (m, 3H), 3.67 (s, 1H). ESIMS m/z 535.4 [M + 2H2O]+.
Compound 15: yield 25%; Yellow liquid; Rf = 0.85; 1H-NMR (400 MHz, CDCl3) δ 7.72 (t, J = 8.6 Hz, 1H), 7.53 (d, J = 5.13 Hz, 1H), 7.36 (s, 1H), 7.07 (s, 1H), 6.70 (m, 8H), 6.10 (m, 1H), 5.84 (m, 1H), 5.60 (m, 1H), 5.40–5.34 (m, 3H), 3.67 (s, 2H), 2.40. ESIMS m/z 405.2 [M + H]+.
Compound 16: yield 23%; Yellow liquid; Rf = 0.87; 1H-NMR (400 MHz, CDCl3) δ 7.79 (m, 1H), 7.52 (d, J = 7.85Hz, 1H), 6.71 (s, 7H), 5.87 (m, 1H), 5.63 (m, 1H), 5.16 (m, 1H), 5.05–4.98 (m, 3H), 3.67 (s, 3H). ESIMS m/z 421.4 [M + H]+.