4
F. S. Aldawsari et al.
J Enzyme Inhib Med Chem, Early Online: 1–12
1
(E)-3,40,5-Trimethoxystilbene (TMS). In a 250 ml three neck (0.45 g, 70% yield) as colorless needles, mp 97–99 ꢁC. H-NMR
round bottom flask, the phosphonium bromide 1b (1.8 g, (300 MHz, CDCl3) ꢀ 8.12 (d, J ¼ 1.83 Hz, 1H, H-20), 7.80 (dd,
3.6 mmol) and 4-methoxybenzaldehyde (0.5 g, 3.6 mmol) were J ¼ 8.55, 1.83 Hz, 1H, H-60), 7.19 (d, J ¼ 16.47 Hz, 1H, alkene),
mixed in dry THF according to the general procedure described 7.13 (d, J ¼ 8.55 Hz, 1H, H-50), 7.12 (d, J ¼ 16.47 Hz, 1H,
above. The title compound was obtained (0.65 g, 64% yield), as a alkene), 6.73 (d, J ¼ 2.46 Hz, 2H, H-2 and H-6), 6.41
colorless needles, m.p. ¼ 55–56 ꢁC (reported 55–57 ꢁC)17. (t, J ¼ 2.40 Hz, 1H, H-4), 3.87 (s, 3H, CH3OCO), 3.80 (s, 6H,
1H-NMR (600 MHz, CDCl3) ꢀ 7.44 (d, J ¼ 8.4 Hz, 2H, H-20 & CH3O), 2.30 (s, 3H, CH3COO). 13C-NMR (300 MHz, CDCl3) ꢀ
H-60), 7.04 (d, J ¼ 16.2 Hz, 1H, alkene), 6.90 (d, J ¼ 16.8 Hz, 1H, 169.67, 164.75, 160.96, 149.77, 138.70, 135.30, 131.32, 130.10,
alkene), 6.89 (d, J ¼ 8.4 Hz, 2H, H-30 & H-50), 6.65 (d, J ¼ 2.4 Hz, 129.66, 127.06, 124.09, 123.26, 104.65, 100.36, 55.36, 52.25,
2H, H-2 & H-6), 6.37 (d, J ¼ 2.4 Hz, 1H, H-4), 3.83 (s, 9H, 20.96. ESI-MS m/z; 378.9 [M + Na]+.
CH3O). 13C-NMR (300 MHz, CDCl3) ꢀ 160.98, 159.42, 139.72,
129.97, 128.76, 127.77, 126.62, 114.16, 104.39, 99.68, 55.36.
(E)-3,40,5-Trimethoxy-30-(methoxycarbonyl)stilbene (7). In
a
250 ml three neck round bottom flask, the phosphonium bromide
1b (3.3 g, 6.7 mmol) and the aldehyde 2a (1.17 g, 6.03 mmol)
were mixed in dry THF as described in the general procedure
described above. The title compound was obtained (1.38 g, 70%
(E)-4,40-Dimethoxy-3-(methoxycarbonyl)stilbene
(3). In
a
250 ml three neck round bottom flask, the phosphonium bromide
1a (3.0 g, 6.5 mmol) and the aldehyde 2a (1.15 g, 5.9 mmol) were
mixed in dry THF according to the general procedure described
above. The title compound was obtained (1.25 g, 71% yield), as a
white solid, m.p. ¼ 133–134 ꢁC. 1H-NMR (600 MHz, CDCl3) ꢀ
7.93 (d, J ¼ 2.4 Hz, 1H, H-20), 7.58 (dd, J ¼ 8.4, 2.4 Hz, 1H, H-60),
7.43 (d, J ¼ 9 Hz, 2H, H-2 and H-6), 6.98 (d, J ¼ 16.2 Hz, 1H,
alkene), 6.97 (d, J ¼ 8.4 Hz, 1H, H-50), 6.91 (d, J ¼ 18.3 Hz, 1H,
alkene), 6.89 (d, J ¼ 9 Hz, 2H, H-3 and H-5), 3.92 (s, 3H, CH3O),
3.92 (s, 3H, CH3OCO), 3.83 (s, 3H, CH3O). 13C-NMR (300 MHz,
CDCl3) ꢀ 166.61, 159.20, 158.25, 131.03, 130.07, 130.04, 129.36,
129.20, 127.52, 127.38, 125.01, 120.16, 114.13, 112.30, 56.16,
55.32, 52.09. ESI-MS m/z; 321.0 [M + Na]+. Anal. calcd for
C18H18O4: C 72.47, H 6.08, found: C 72.49, H 6.19.
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yield) as a white solid, m.p. ¼ 102–103 ꢁC. H-NMR (300 MHz,
CD3OD) ꢀ 7.92 (d, J ¼ 1.83 Hz, 1H, H-20), 7.72 (dd, J ¼ 8.55,
2.46 Hz, 1H, H-60), 7.12 (d, J ¼ 9.15 Hz, 1H, H-50), 7.11 (d,
J ¼ 14.01 Hz, 1H, alkene), 7.00 (d, J ¼ 16.47 Hz, 1H, alkene),
6.70 (d, J ¼ 2.43 Hz, 2H, H-2 and H-6), 6.38 (t, J ¼ 2.46 Hz, 1H,
H-4), 3.89 (s, 3H, CH3OCO), 3.87 (s, 3H, CH3O), 3.80 (s, 6H,
CH3O). 13C-NMR (300 MHz, CDCl3) ꢀ 166.32, 160.80, 158.46,
139.08, 131.21, 129.58, 129.31, 127.58, 127.41, 120.03, 112.15,
104.26, 99.76, 99.65, 55.96, 55.16, 51.91, 29.57. ESI-MS m/z;
351.0 [M + Na]+.
General procedure for synthesis of compounds 8–10. The
corresponding E stilbene (3 or 7) was dissolved in dry
dichloromethane using a heat-dried three neck round bottom
flask equipped with a magnetic stirrer. This solution was cooled
down using dry ice and acetone, to about ꢂ60 ꢁC; then a solution
of boron tribromide (1 M in CH2Cl2) was added dropwise. After
adding the deprotecting agent, the ice bath was withdrawn to
allow the reaction mixture to warm up to room temperature and it
was stirred for 1–4 h. The reaction was quenched by adding water
(60 ml; very slowly), and the product was extracted with
dichloromethane (20 ml). The combined organic phases were
dried using sodium sulfate, and the solvent was evaporated under
vacuum. Finally, the product was purified by silica gel column
chromatography using a mixture of ethyl acetate/methanol (8:2) to
afford the corresponding hydroxylated stilbenes.
(E)-4-Acetoxy-40-methoxy-3-(methoxycarbonyl)stilbene (4). In a
250 ml three neck round bottom flask, the phosphonium bromide
1a (1.25 g, 2.7 mmol) and the aldehyde 2b (0.42 g, 1.9 mmol)
were mixed in dry THF according to the general procedure
described above. The title compound was obtained (0.43 g, 70%
yield), as a white solid, mp 123–125 ꢁC. 1H-NMR (300 MHz,
CDCl3) ꢀ 8.11 (d, J ¼ 2.43 Hz, 1H, H-20), 7.62 (dd, J ¼ 8.55,
2.43 Hz, 1H, H-60), 7.44 (d, J ¼ 9.15 Hz, 2H, H-2 and H-6), 7.07
(d, J ¼ 7.95 Hz, 1H, H-50), 7.06 (d, J ¼ 15.87 Hz, 1H, alkene),
6.93 (d, J ¼ 16.47 Hz, 1H, alkene), 6.90 (d, J ¼ 9.15 Hz, 2H, H-3
and H-5), 3.90 (s, 3H, CH3OCO), 3.81 (s, 3H, CH3O), 2.36 (s, 3H,
CH3CO). 13C-NMR (300 MHz, CDCl3): ꢀ 169.55, 164.72, 159.43,
149.24, 135.71, 130.87, 129.47, 129.39, 129.14, 127.74, 124.29,
123.88, 123.05, 114.03, 55.13, 52.06, 20.83). ESI-MS m/z; 348.9
[M + Na]+.
(E)-4,40-Dihydroxy-30-(hydroxycarbonyl)stilbene (8). In a 50 ml
three neck round bottom flask, compound 3 (0.26 g, 0.87 mmol)
and a solution of boron tribromide (5.2 ml; 6 Eq) were mixed in
dry dichloromethane according to the general procedure described
above. Compound 8 was obtained (0.135 g, 60% yield) as an off-
white solid, m.p. ¼ 237–240 ꢁC (reported 241–243 ꢁC)19. 1H-
NMR (300 MHz, CD3OD) ꢀ 7.94 (d, J ¼ 2.46 Hz, 1H, H-20), 7.66
(dd, J ¼ 8.55, 2.43 Hz, 1H, H-60), 7.35 (d, J ¼ 8.55 Hz, 2H, H-2
and H-6), 6.96 (d, J ¼ 16.4 Hz, 1H, alkene), 6.90 (d, J ¼ 8.52 Hz,
1H, H-50), 6.89 (d, J ¼ 15.87 Hz, 1H, alkene), 6.75 (d,
J ¼ 8.55 Hz, 2H, H-3 & H-5). ESI-MS m/z; 256.8 [M + H]+.
(E)-40-Acetoxy-3,30,5-trimethoxystilbene (5). In a 250 ml three
neck round bottom flask, the phosphonium bromide 1b (1.2 g,
2.4 mmol) and vanillin acetate 2c (0.45 g, 2.3 mmol) were mixed
in dry THF according to the general procedure described above.
The title compound was obtained (0.5 g, 65% yield) as white
crystals, m.p. ¼ 118–120 ꢁC (reported 120–122 ꢁC)18. 1H-NMR
(600 MHz, CDCl3) ꢀ 7.09 (dd, J ¼ 5.4 & 1.8 Hz, 1H, H-60), 7.07
(d, J ¼ 1.8 Hz, 1H, H-20), 7.04 (d, J ¼ 16.2 Hz, 1H, alkene), 7.02
(d, J ¼ 8.4 Hz, 1H, H-50), 6.97 (d, J ¼ 16.8 Hz, 1H, alkene), 6.66
(d, J ¼ 1.8 Hz, 2H, H-2 & H-6), 6.40 (t, J ¼ 2.4 Hz, 1H, H-4), 3.89
(s, 6H, CH3O), 3.83 (s, 3H, CH3O), 2.32 (s, 3H, CH3CO).
13C-NMR (300 MHz, CDCl3) ꢀ 169.00, 160.96, 151.17, 139.36,
139.07, 136.20, 128.95, 128.53, 122.91, 119.30, 110.11, 104.58,
100.11, 55.89, 55.38, 20.70). ESI-MS m/z; 351.0 [M + Na]+.
(E)-3,40,5-Trihydroxy-30-(hydroxycarbonyl)stilbene (9). In
a
50 ml three neck round bottom flask, compound 7 (0.58 g,
1.7 mmol) and a solution of boron tribromide (13.6 ml; 8 Eq) were
mixed in dichloromethane according to the general procedure
reported above. The product 9 was obtained (0.2 g, 41% yield), as
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(E)-40-Acetoxy-3,5-dimethoxy-30-(methoxycarbonyl)stilbene
a yellow solid, m.p. ¼ 213–215 ꢁC. H-NMR (300 MHz, CD3OD)
(6). In a 250 ml three neck round bottom flask, the phosphonium ꢀ 7.95 (d, J ¼ 2.46 Hz, 1H, H-20), 7.68 (dd, J ¼ 8.55, 2.43 Hz, 1H,
bromide 1b (0.9 g, 1.82 mmol) and the aldehyde 2b (0.4 g, H-60), 6.98 (d, J ¼ 16.47 Hz, 1H, alkene), 6.91 (d, J ¼ 8.52 Hz,
1.82 mmol) were mixed in dry THF according to the general 1H, H-50), 6.86 (d, J ¼ 16.47 Hz, 1H, alkene), 6.46 (d,
procedure described above. The title compound was obtained J ¼ 1.83 Hz, 2H, H-2 and H-6), 6.16 (t, J ¼ 2.46 Hz, 1H, H-4).