Curcuminoid Antioxidants
J ournal of Natural Products, 1998, Vol. 61, No. 5 611
C2H5OH (30 mL) was added 1.4 N NaOH solution (C2H5-
OH-H2O 4:5, 70 mL) at 23 °C. The mixture was stirred
for 16 h, then poured into saturated NaCl and extracted
3 times with CH2Cl2. The combined CH2Cl2 layer was
dried over anhydrous Na2SO4 and evaporated. The
residue was crystallized with ether, giving 4 (26.6 g,
97%) as a yellow powder. Yellow plates of 4 were
obtained by recrystalization of the powder with CH3-
OH: mp 108.0-109.0 °C; 1H NMR δ (CDCl3) 8.21 (1H,
d, J ) 16 Hz), 7.69 (1H, dd, J ) 7.2, 2 Hz), 7.62 (1H, d,
J ) 2 Hz), 7.60 (1H, d, J ) 16 Hz), 7.31 (1H, d, J ) 7.2
Hz), 7.11 (1H, t, J ) 7.2 Hz), 6.97 (1H, d, J ) 8.0 Hz),
6.92 (1H, d, J ) 8.0 Hz), 5.16 (2H, s), 3.95 (6H, s), 3.83
(3H, s), 3.60 (3H, s); IR (film) νmax 1657; EIMS m/z 358
[M]+; anal. C 66.82%, H 5.99%, calcd for C20H22O6, C
67.02%, H 6.19%.
giving 6 (7.1 g, quantitative yield) as viscous oil: 1H
NMR δ (CDCl3) 7.67 (1H, dd, J ) 8.0, 2.0 Hz), 7.56 (1H,
d, J ) 2 Hz), 6.88 (1H, t, J ) 8.0 Hz), 6.83 (1H, dd, J )
7.8, 1.5 Hz), 6.83 (1H, d, J ) 7.8 Hz), 6.81 (1H, d, J )
7.8 Hz), 6.05 (1H, br s), 3.97 (3H, s), 3.96 (3H, s), 3.90
(3H, s), 3.80 (1H, m), 3.42 (1H, dd, J ) 16, 4 Hz), 3.02
(1H, dd, J ) 16, 5 Hz), 1.33 (3H, d, J ) 7 Hz); IR (film)
νmax 3442, 1673; HRMS m/z 330.1474 (calcd for C19H22O5,
330.1466).
By similar procedures, 13 (6.4 g) was synthesized in
84% yield from 12 (8.5 g): mp 104.5-105.5 °C; 1H NMR
δ (CDCl3) 7.34 (1H, s), 6.80 (2H, m), 6.70 (1H, m), 6.48
(1H, s), 6.26 (1H, br s), 3.79 (1H, m), 3.42 (1H, dd, J )
17, 5 Hz), 3.23 (1H, dd, J ) 17, 7 Hz), 1.30 (3H, d, J )
7.3 Hz); IR (CHCl3) νmax 3500, 1660; EIMS m/z 360 [M]+;
anal. C 66.42%, H 6.73%, calcd for C20H24O6, C 66.65%,
H 6.71%.
By similar procedures using 2′,4′,5′-trimethoxy-
acetophenone instead of 3′,4′-dimethoxyacetophenone,
11 (12.2 g) was obtained in 84% yield from 3 (7.3 g):
Syn th esis of Dia ceta tes 7 a n d 14. To a solution
of 6 (7.1 g) in CH3OH (300 mL) was added NaBH4 (3.5
g) at 23 °C. After stirring for 10 min at 23 °C, the
mixture was poured into H2O, extracted four times with
CH2Cl2, dried over Na2SO4, and concentrated. To the
residue were added Ac2O (56 mL) and pyridine (56 mL)
at 23 °C. After standing for 3 h, the solvent was
removed in vacuo, and the residue was purified by Si
gel column chromatography (EtOAc-hexane, 1:2) to
give diacetate 7 as a 3:1 mixture of stereoisomers (7.9
1
mp 108.5-109.5 °C; H NMR (CDCl3) 8.13 (1H, d, J )
16 Hz), 7.62 (1H, d, J ) 16 Hz), 7.39 (1H, s), 7.23(1H,
d, J ) 7.8 Hz), 7.16 (1H, t, J ) 7.8 Hz), 6.94 (1H, d, J
) 7.8 Hz), 6.54 (1H, s), 5.16 (2H, s), 3.97 (3H, s), 3.93
(3H, s), 3.89(3H, s), 3.85(3H, s), 3.61 (3H, s); IR (CHCl3)
νmax 1650; EIMS m/z 388 [M]+; anal. C 65.07%, H
6.24%, calcd for C21H24O7, C 64.94%, H 6.23%.
Syn th esis of Keton es 5 a n d 12. To a solution of
CuI (2.4 g) in dry ether (48 mL) was added dropwise
CH3Li (1.5 N solution in ether) at 0 °C under N2
atmosphere. After stirring 5 min, a THF solution (15
mL) of 4 (3.0 g) was added dropwise to the solution for
10 min. After stirring for 5 min at 0 °C, the excess
(CH3)2CuLi was decomposed by CH3COOH and then by
1N HCl. The mixture was extracted three times with
CH2Cl2. The CH2Cl2 layers were combined, dried over
Na2SO4, and evaporated. The residue was purified by
Si gel column chromatography (ethyl acetate-hexane,
1:2), giving 5 (2.95 g, 94%) as colorless powder. Color-
less prisms of 5 were obtained by recrystallization with
1
g, 88%): colorless oil, H NMR δ (CDCl3) major isomer
7.19 (1H, t, J ) 7.8 Hz), 6.93-6.78 (5H, m), 5.62 (1H,
br t, J ) 7.2 Hz), 3.88 (3H, s), 3.87 (3H, s), 3.82 (3H, s),
2.82 (1H, m), 2.31 (1H, m), 2.23 (3H, s), 2.00 (3H, s),
1.92 (1H, m), 1.39 (3H, d, J ) 7.2 Hz); IR (film) νmax
1765, 1735; EIMS m/z 416 [M]+; anal. C 66.57%, H
6.69%, calcd for C23H28O7, C 66.33%, H 6.78%.
By similar procedures, 14 (7.2 g) was synthesized in
97% yield from 13 (6.0 g): a 1:1 mixture of streoisomers;
1H NMR δ (CDCl3) 7.15 (1H, t, J ) 8 Hz), 7.14 (1H, t, J
) 8 Hz), 6.88 (1H, d, J ) 8 Hz), 6.86 (1H, d, J ) 8 Hz),
6.80 (1H, d, J ) 8 Hz), 6.79 (1H, s), 6.78 (1H, d, J ) 8
Hz), 6.77 (1H, s,), 6.50 (1H, s), 6.49 (1H, s), 6.16 (1H,
dd, J ) 9, 4 Hz), 6.04 (1H, t, J ) 6 Hz), 3.89 (3H, s),
3.88 (3H, s), 3.84 (3H, s), 3.82 (3H, s), 3.81 (6H, s), 3.79
(3H, s), 3.78 (3H, s), 2.94 (1H, m), 2.79 (1H, m), 2.29
(3H, s), 2.25-2.15 (3H, m), 2.11 (3H, s), 2.10 (3H, s),
2.00 (3H, s), 1.88 (1H, m), 1.12 (3H, d, J ) 7 Hz), 1.11
(3H, d, J ) 7 Hz); IR (CHCl3) νmax 1760, 1725. HRMS
m/z 446.1948 (calcd for C24H30O8, 446.1941).
1
CH3OH-H2O: mp 95.5-97.0 °C; H NMR δ (CDCl3)
7.64 (1H, dd, J ) 8.4, 2.0 Hz), 7.53 (1H, d, J ) 1.6 Hz),
7.06 (1H, t, J ) 8.0 Hz), 6.89 (1H, dd, J ) 8.8, 1 Hz),
6.87 (1H, d, J ) 8.8 Hz), 6.80 (1H, dd, J ) 8.0, 1.2 Hz),
5.12 (2H, s), 3.98 (1H, m), 3.94 (3H, s), 3.93 (3H, s), 3.84
(3H, s), 3.57 (3H, s), 3.30 (1H, dd, J ) 16, 4.4 Hz), 3.06
(1H, dd, J ) 16, 9.2 Hz), 1.30 (3H, d, J ) 7.2 Hz); IR
(film) νmax 1673; EIMS m/z 374 [M]+; anal. C 67.24%,
H 7.08%, calcd for C21H26O6, C 67.36%, H 7.00%.
Syn th esis of Olefin s 8 a n d 15. The DMSO solution
(40 mL) of 7 (7.8 g) was heated for 1 h at 160 °C. After
cooling, DMSO was removed in vacuo, and the residue
was purified by Si gel column chromatography (EtOAc-
hexane 1:2) to give 8 (5.6 g, 84%). Colorless cubes of 7
were obtained by recrystallization with EtOAc-hex-
ane: mp 78.0-79.0 °C; 1H NMR δ (CDCl3) 7.26 (1H, d,
J ) 1.2 Hz), 7.18 (1H, t, J ) 8 Hz), 6.92-6.85 (3H, m),
6.79 (1H, d, J ) 8.0 Hz). 6.35 (1H, d, J ) 16 Hz), 6.19
(3H, dd, J ) 16, 5.6 Hz), 3.88 (3H, s), 3.87 (3H, s), 3.83
(3H, s), 3.77 (1H, m), 2.30 (3H, s), 1.42 (3H, d, J ) 6.8
Hz); IR (film) νmax 1765; EIMS m/z 356 [M]+; anal. C
70.82%, H, 6.79%, calcd for C21H24O5, C 70.76%, H
6.79%.
Using similar procedures, 12 (10.2 g) was synthesized
1
in 98% yield from 11 (10.0 g): mp 105.0-106.0 °C; H
NMR δ (CDCl3) 7.36 (1H, s), 7.04 (1H, t, J ) 7.8 Hz),
6.86 (1H, d, J ) 7.8 Hz), 6.77 (1H, d, J ) 7.8 Hz), 6.48
(1H, s), 5.09 (2H, s), 3.98 (1H, m), 3.92 (3H, s), 3.88 (3H,
s), 3.85 (3H, s), 3.82 (3H, s), 3.58 (3H, s), 3.32 (1H, dd,
J ) 17, 4 Hz), 3.20 (1H, dd, J ) 17, 9 Hz), 1.26 (3H, d,
J ) 6.8 Hz); IR (CHCl3) νmax 1660; EIMS m/z 404 [M]+;
anal. C 65.13%, H 6.96%, calcd for C22H28O7, C 65.33%,
H 6.98%.
Syn th esis of P h en ols 6 a n d 13. To a solution of 5
(8.0 g) in CH3OH (240 mL) was added 1N HCl (136 mL).
The mixture was stirred at 60 °C for 5 min, then poured
into H2O and extracted four times with CH2Cl2. The
CH2Cl2 layer was dried over Na2SO4 and purified by Si
gel column chromatography (EtOAc- hexane, 1:1),
By similar procedures, 15 (7.0 g) was synthesized in
quantitative yield from 14 (7.0 g): mp 118.0-119.0 °C;
1H NMR δ (CDCl3) 7.17 (1H, t, J ) 8 Hz), 6.93 (1H, s),