2328
K. Nakagawa-Goto et al. / Bioorg. Med. Chem. 13 (2005) 2325–2330
00 00
proton), 7.68–7.61 (m, 2H, Ar-2 ,6 -H), 6.95–6.87 (m,
2H, Ar-3 , 5 -H), 3.95 (s, 3H, 5-OCH ), 3.85 (s, 3H,
of the A-ring might confer high selectivity against cancer
cell lines. Additional experiments are in progress.
00
00
3
Ph–OCH ), 2.00 (s, 3H, 4-CH ), 1.38 (s, 6H, 6-
3
3
+
CH · 2). MS m/z 343 (M +1). Anal. Calcd for
3
4
. Experimental section
C H O : C, 70.16; H, 6.48; O, 23.36. Found: C,
6
2
0
22
5
9.91; H, 6.60; O, 23.33.
All chemicals and solvents were used as purchased. All
melting points were measured on a Fisher–Johns melt-
ing point apparatus without correction. H NMR and
4.1.3. 2-[1-Hydroxy-3-(3-methoxyphenyl)-allylidene]-5-
methoxy-4,6,6-trimethyl-cyclohex-4-ene-1,3-dione (4).
Method I: 66% yield. mp 72–73 ꢁC (CH Cl –hexane).
1
1
3
C NMR spectra were recorded on a Varian Gemini
000 (300 MHz) NMR spectrometer with TMS as the
2
2
2
IR (KBr): 2976, 2938, 1656, 1624, 1580, 1514, 1450,
ꢀ
1
1
internal standard. All chemical shifts are reported in
ppm. NMR spectra were referenced to the residual sol-
vent peak; chemical shifts d in ppm; apparent scalar cou-
pling constants J in Hz. Mass spectral data were
obtained on a TRIO 1000 mass spectrometer. IR spectra
were recorded on a Perkin–Elmer 1320 spectrophoto-
meter. Analytical thin-layer chromatography (TLC)
was carried out on Merck precoated aluminum silica
gel sheets (Kieselgel 60 F-254). All target compounds
1425, 1256 cm . H NMR (CDCl ): d 19.16 (s) and
3
18.75 (s) (3.5:1, 1H, chelated-OH), 8.50 (d) and 8.29
(d) (1:3.5, 1H, J = 15.5 Hz, trans-olefinic proton), 7.91
(d) and 7.89 (d) (1:3.5, 1H, J = 15.5 Hz, trans-olefinic
0
0
00 00
proton), 7.34–7.12 (m, 3H, Ar-2 ,5 ,6 -H), 6.98–6.90
00
(m, 2H, Ar-4 -H), 3.95 (s) and 3.88 (s) (3.5:1, 3H,
5-OCH ), 3.84 (s, 3H, Ph-OCH ), 1.99 (s) and 1.94
(s) (3.5:1, 3H, 4-CH ), 1.46 (s) and 1.37 (s) (1:3.5, 6H,
3
3
3
+
6-CH · 2). MS m/z 343 (M +1).
3
1
were characterized by H and IR spectral analyses and
MS analyses.
4.1.4. 2-[1-Hydroxy-3-(2-methoxyphenyl)-allylidene]-5-
methoxy-4,6,6-trimethyl-cyclohex-4-ene-1,3-dione
(5).
Method I: 89% yield. mp 127–128 ꢁC (CH Cl –hexane).
IR (KBr): 2976, 2938, 1657, 1615, 1513, 1487, 1465,
4
.1. General procedures for the aldol reactions
2
2
ꢀ
1
1
Method I: A solution of acetyl compound (11, 12, or 15)
in EtOH–50% aq KOH (1:1, v/v) and an appropriate
aldehyde (excess) was stirred at room temperature. After
the reaction was complete by TLC analysis, the mixture
was poured into ice-cold 1 N HCl, then extracted with
CH Cl . The extract was washed with brine, dried over
1423, 1246 cm . H NMR (CDCl ): d 19.16 (s) and
3
18.82 (s) (2.5:1, 1H, chelated-OH), 8.54 (d) and 8.38
(d) (1:2.5, 1H, J = 15.5 Hz, trans-olefinic proton), 8.39
(d) and 8.31 (d) (1:2.5, 1H, J = 15.5 Hz, trans-olefinic
proton), 7.79 (dd) and 7.76 (dd) (1:2.5, 1H, J = 6.9
00
and 1.2 Hz, Ar-6 -H), 7.37 (ddd) and 7.35 (ddd) (1:2.5,
00
2
2
Na SO , and concentrated in vacuo. The residue was
2
1H, J = 8.2, 6.9 and 1.2 Hz, Ar-4 -H), 7.00–6.87 (m,
00
4
00
chromatographed on silica gel with EtOAc–hexane as
eluent to afford the target compound, which was crystal-
lized from CH Cl –hexane.
2H, Ar-3 ,5 -H), 3.94 (s) and 3.90 (s) (2.5:1, 3H, 5-
OCH ), 3.89 (s) and 3.87 (s) (2.5:1, 3H, Ph–OCH ),
1.98 (s) and 1.94 (s) (2.5:1, 3H, 4-CH ), 1.45 (s) and
3
3
2
2
3
+
1
.36 (s) (1:2.5, 6H, 6-CH · 2). MS m/z 343 (M +1).
3
Method II: A solution of 11 and 4-hydroxybenzalde-
hyde (excess) in anhydrous piperidine (excess) was
heated at reflux. The reaction was worked up following
the procedure in method I.
Anal. Calcd for C H O : C, 70.16; H, 6.48; O, 23.36.
20 22 5
Found: C, 69.94; H, 6.46; O, 23.11.
4.1.5. 2-[1-Hydroxy-3-(4-hydroxyphenyl)-allylidene]-5-
methoxy-4,6,6-trimethyl-cyclohex-4-ene-1,3-dione (6).
Method II: 35% yield (based on recovered starting mate-
4.1.1. 2-[1-Hydroxy-3-(4-bromophenyl)-allylidene]-5-meth-
oxy-4,6,6-trimethylcyclohex-4-ene-1,3-dione (2). Method
rial). mp 234–235 ꢁC (CH Cl –MeOH, lit. 215–
2
2
1
1b
I: 61% yield (based on recovered starting material). mp
1
216 ꢁC). IR (KBr): 2359, 2331, 1647, 1619, 1600,
1518, 1446, 1415, 1148, 830, 771 cm H NMR
ꢀ
1
1
40–141 ꢁC (CH Cl –hexane). IR (KBr): 2976, 2935,
.
2
2
ꢀ
1
1
1
657, 1623, 1517, 1488, 1468, 1429 cm
.
H NMR
(CDCl ): d 19.15 (s) and 18.81 (s) (2:1, 1H, chelated-
3
(
CDCl ): d 19.20 (s) and 18.66 (s) (11:1, 1H, chelated-
OH), 8.32 (d) and 8.14 (d) (1:2, 1H, J = 15.7 Hz, trans-
olefinic proton), 7.91 (d) and 7.89 (d) (1:2, 1H,
J = 15.7 Hz, trans-olefinic proton), 7.54 (d) and 7.53
3
OH), 8.51 (d) and 8.30 (d) (1:11, 1H, J = 15.9 Hz,
trans-olefinic proton), 7.84 (d) and 7.83 (d) (1:11, 1H,
J = 15.9 Hz, trans-olefinic proton), 7.56–7.48 (m, 4H,
Ar-2 ,3 ,5 ,6 -H), 3.95 (s) and 3.88 (s) (11:1, 3H, 5-
OCH ), 1.99 (s) and 1.94 (s) (11:1, 3H, 4-CH ), 1.46
00
00
(d) (1:2, 2H, J = 8.6 Hz, Ar-2 ,6 -H), 6.82 (d) and 6.81
(d) (1:2, 2H, J = 8.6 Hz, Ar-3 ,5 -H), 3.91 (s) and 3.85
(s) (2:1, 3H, 5-OCH ), 2.36 (br s, 1H, Ph-OH), 1.95 (s)
00
00 00 00
00 00
3
3
3
(
s) and 1.36 (s) (1:11, 6H, 6-CH · 2). MS m/z 391 and
and 1.91 (s) (2:1, 3H, 4-CH ), 1.42 (s) and 1.33 (s)
3
3
+
+
3
C, 57.66; H, 4.97; O, 17.18. Found: C, 57.42; H, 4.84.
93 (M , 1:1). Anal. Calcd for C H BrO Æ1/4H O:
(1:2, 6H, 6-CH · 2). MS m/z 327 (M ꢀ1). Anal. Calcd
1
9
19
4
2
3
for C H O : C, 69.50; H, 6.18; O, 24.36. Found: C,
20
1
9
5
6
9.50; H, 6.18; O, 24.36.
4
.1.2. 2-[1-Hydroxy-3-(4-methoxyphenyl)-allylidene]-5-
methoxy-4,6,6-trimethylcyclohex-4-ene-1,3-dione (3).
Method I: 82% yield. mp 99–100 ꢁC (CH Cl –hexane).
0
00
0
4.1.6. 2-(3 -Furan-2 -yl-1 -hydroxy-allylidene)-5-meth-
oxy-4,6,6-trimethyl-cyclohex-4-ene-1,3-dione (7). Meth-
od I: 74% yield (based on recovered starting material).
mp 119–120 ꢁC (CH Cl –hexane). IR (KBr): 3120,
2
2
IR (KBr): 2975, 2934, 1656, 1621, 1600, 1572, 1510,
ꢀ
1 1
1
1
423, 1243, 1171 cm . H NMR (CDCl ): d 19.19 (s,
3
2
2
ꢀ
1
H, chelated-OH), 8.23 (d, 1H, J = 15.5 Hz, trans-ole-
2986, 2945, 1654, 1626, 1558, 1502, 1442, 1414 cm .
H NMR (CDCl ): d 19.07 (s) and 18.71 (s) (2.2:1, 1H,
3
1
finic proton), 7.94 (d, 1H, J = 15.5 Hz, trans-olefinic