Coruscanone A Analogues
Journal of Medicinal Chemistry, 2006, Vol. 49, No. 26 7883
2-[(E)-3-(Furan-2-yl)-1-hydroxyallylidene]-4-methylcyclopent-
4-ene-1,3-dione (34). Yield, 50% from 26, yellow powder; 1H NMR
(400 MHz, benzene-d6, Z/E-isomers) δ 12.64/12.35 (1H each, br
s, OH), 8.03/7.98 (1H each, d, J ) 16 Hz, H-7), 7.48 (1H × 2, d,
J ) 16 Hz, H-8), 6.82 (1H × 2, br d, H-12), 6.05 (1H × 2, br d,
H-10), 5.95 (1H × 2, br d, H-11), 5.85 (1H × 2, s, H-5), 1.52 and
1.45 (3H each, s, Me); 13C NMR (100 MHz, CDCl3, Z/E-isomers)
δ 201.1, 200.6, 192. 0, 191.5, 167.5, 167.3, 157.9, 153.9, 151.7
(2C), 145.7, 145.6, 140.6, 136.7, 129.0, 128.9, 116.03, 115.99,
115.4, 115.3, 112.8 (2C), 103.2, 103.0, 11.3, 10.5; HRESIMS m/z
[M + H]+ 231.0641(calcd for C13H11O4, 231.0652).
138.1, 135.5 (2C), 130.8, 130.7, 130.4 (2C), 130.0, 129.1 (4C),
129.0 (3C), 128.9 (4C), 128.8 (2C), 128.6 (4C), 121.4, 121.2, 110.0,
109.8, 64.8, 64.7; HRESIMS m/z [M + H]+ 317.1160 (calcd for
C21H17O3, 317.1172). Anal. HPLC [tR (min) (content)]: 9.56
(99.5%) from solvent a or 11.70 (99.7%) from solvent b.
2-[(E)-3-(4-Chlorophenyl)-1-methoxyallylidene]-4-methylcy-
clopent-4-ene-1,3-dione (40). Yield, 95% from methylation of 33,
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yellow powder; H NMR (400 MHz, benzene-d6, Z/E-isomers) δ
8.30/8.23 (1H each, d, J ) 16 Hz, H-7), 7.39 (1H × 2, d, J ) 16
Hz, H-8), 7.08 (2H × 2, d, J ) 7.6 Hz, H-11, 13), 6.94 (2H × 2,
d, J ) 7.2 Hz, H-10, 14), 6.22/6.19 (1H each, s, H-5), 3.98/3.93
(3H each, s, OMe), 1.60 (6H, br s, H-6); 13C NMR (100
MHz, CDCl3, Z/E-isomers) δ 195.2, 194.0, 192.4, 191.6, 168.4,
168.2, 157.0, 156.5, 141.0 (2C), 140.7, 140.4, 136.1 (2C), 134.0
(2C), 129.6 (2C), 129.5 (2C), 129.2 (4C), 121.9, 121.7, 108.9, 108.8,
64.8, 64.7, 11.2, 11.1; HRESIMS m/z [M + H]+ 289.0611 (calcd
for C16H14O3Cl, 289.0626). Anal. HPLC [tR (min) (content)]: 7.68
(96.7%) from solvent a or 7.46 (99.4%) from solvent b.
2-[(E)-1-Hydroxy-3-(thiophen-2-yl)allylidene]-4-methylcyclo-
pent-4-ene-1,3-dione (35). Yield, 50% from 27, yellow powder;
1H NMR (400 MHz, CDCl3, Z/E-isomers) δ 12.08/11.98 (1H each,
br s, OH), 7.90 (1H × 2, d, J ) 16 Hz, H-7), 7.51/7.49 (1H each,
brd, J ) 16 Hz, H-8), 7.50 (1H × 2, br s, H-12), 7.37 (1H × 2, br
d, H-10), 7.11 (1H × 2, m, H-11), 6.68/6.60 (1H each, s, H-5),
2.11/2.12 (3H each, s, Me); 13C NMR (100 MHz, CDCl3, Z/E-
isomers) δ 201.1, 200.5, 192.1, 191.6, 167.5, 167.3, 157.9, 154.0,
140.6 (2C), 136.8 (2C), 135.6, 135.5, 131.6, 131.5, 130.0, 129.9,
128.4 (2C), 116.4, 116.3, 103.0, 102.8, 11.3, 10.5; HRESIMS m/z
[M + H]+ 247.0411 (calcd for C13H11O3S, 247.0423).
2-[(E)-3-(Furan-2-yl)-1-methoxyallylidene]-4-methylcyclopent-
4-ene-1,3-dione (41). Yield, 90% from methylation of 34, yellow
1
powder; H NMR (400 MHz, benzene-d6, Z/E-isomers) δ 8.42/
8.35 (1H each, d, J ) 16 Hz, H-7), 7.33 (1H × 2, d, J ) 16 Hz,
H-8), 6.89 (1H × 2, brd, H-12), 6.20 (1H × 2, br d), 6.15 (1H ×
2, br d), 5.91 (1H × 2, br s, H-5), 3.94/3. 89 (3H each, s, OMe),
1.59/1.58 (3H each, s, Me); 13C NMR (100 MHz, CDCl3, Z/E-
isomers) δ 195.0, 193.9, 192.5, 191.7, 168.6, 168.4, 156.6, 156.4,
152.2 (2C), 145.3 (2C), 140.4, 140.2, 128.8 (2C), 119.2, 119.0,
115.2 (2C), 112.7 (2C), 108.7, 108.6, 64.6, 64.5, 11.1, 11.0;
HRESIMS m/z [M + H]+ 245.0793 (calcd for C14H13O4, 245.0809).
Anal. HPLC [tR (min) (content)]: 4.22 (98.7%) from solvent a or
3.88 (98.0%) from solvent b.
2-[Hydroxy(phenyl)methylene]-4-methylcyclopent-4-ene-1,3-
1
dione (36). Yield, 52% from 28, pale-yellow powder; H NMR
(400 MHz, CDCl3, Z/E-isomers) δ 8.06 (2H × 2, d, J ) 8 Hz,
H-8, 12), 7.59 (1H × 2, t, J ) 8 Hz, H-10), 7.50 (2H × 2, t, J )
8 Hz, H-9, 11), 11), 6.74/6.59 (1H each, q, J ) 1.2 Hz, H-5), 2.12/
2.09 (3H each, s, J ) 1.2 Hz, Me); 13C NMR (100 MHz, CDCl3,
Z/E-isomers) δ 202.7, 202.1, 190.3, 189.8, 173.8, 173.5, 157.5,
153.0, 140.4, 136.2, 133.0, 131.2, 129.9 (2C), 129.7 (4C),128.0
(4C), 103.2, 102.9, 11.4, 10.4; HRESIMS m/z [M + H]+ 215.0681
(calcd for C13H11O3, 215.0703).
2-[(E)-1-Methoxy-3-(thiophen-2-yl)allylidene]-4-methylcyclo-
pent-4-ene-1,3-dione (42). Yield, 90% from methylation of 35,
2-[(E)-3-[4-O-(tert-Butyldimethylsilyl)]phenyl-1-methoxy-
allylidene]-4-methylcyclopent-4-ene-1,3-dione (37). Yield, 50%
from 29, pale-yellow oil; 1H NMR (400 MHz, CDCl3, Z/E-isomers)
δ 12.1/12.0 (1H each, br s, OH), 7.76 (1H × 2, d, J ) 16 Hz,
H-7), 7.61/7.58 (1H each, d, J ) 16 Hz, H-8), 7.56 (2H × 2, dd,
J ) 8, 2 Hz, H-10, 14), 6.89 (2H × 2, d, J ) 8 Hz, H-11, 13),
6.67/6.68 (1H each, q, J ) 1.6 Hz, H-5), 2.12/2.11 (3H each, d, J
) 1.6 Hz, Me), 1.02 (6H × 2, s, Me), 0.25 (6H × 2, s, 2 × Me).
General Procedure for Alkylation of Cyclopentenediones
30-37. To a solution of the cyclopentenedione (1 mmol) in dry
acetone (20 mL) under argon was added K2CO3 (1.5 mmol). After
the mixture was refluxed for 5 min, Me2SO4 or Et2SO4 (1.2 mmol)
was added to the deep-yellow solution, and reflux was continued
for 1-3 h. After completion of the reaction, K2CO3 was removed
by filtration. The filtrate was concentrated to dryness, and the resi-
due was subjected to reversed-phase RP-18 column chromatography
using aqueous MeOH (60-80%) to give the desired product.
2-[(E)-1-Methoxy-3-phenylallylidene]-4-methylcyclopent-4-
ene-1,3-dione (1, Coruscanone A). Yield, 93% from methylation
of 30; see ref 3 for physical and spectroscopic data including NMR
signal assignments. Anal. HPLC [tR (min) (content)]: 5.65 (97.7%)
from solvent a or 5.72 (99.0%) from solvent b.
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yellow powder; H NMR (400 MHz, benzene-d6, Z/E-isomers) δ
8.29/8.23 (1H each, d, J ) 16 Hz, H-7), 7.66 (1H, d, J ) 16 Hz,
H-8), 6.85 (1H × 2, br d), 6.71(1H × 2, br d), 6.54 (1H × 2, br d),
6.19/6.16 (1H each, s, H-5), 3.94/3.89 (3H each, s, OMe), 1.60/
1.59 (3H each, s, Me); 13C NMR (100 MHz, CDCl3, Z/E-isomers)
δ 195.2, 194.0, 192.5, 191.7, 168.6, 168.4, 156.7, 156.3, 141.3 (2C),
140.5, 140.2, 135.3, 135.2, 130.9, 130.8, 129.3 (2C), 128.3 (2C),
120.4, 120.2, 108.4 (2C), 64.7, 64.6, 11.15, 11.1; HRESIMS m/z
[M + H]+ 231.0564 (calcd for C14H13O3S, 261.0580). Anal. HPLC
[tR (min) (content)]: 4.77 (95.8%) from solvent a or 4.64 (96.0%)
from solvent b.
2-[Methoxy(phenyl)methylene]-4-methylcyclopent-4-ene-1, 3-di-
one (43). Yield, 88% from methylation of 36, pale-yellow powder;
1H NMR (400 MHz, CDCl3, Z/E-isomers) δ 7.50 (3H × 2, m),
7.29 (2H × 2, m), 6.70/6.57 (1H each × 2, s, H-5), 3.77/3.76 (3H
each × 2, s, OMe), 2.06/1.95 (3H each × 2, s, Me); 13C NMR
(100 MHz, CDCl3, Z/E-isomers) δ 193.7, 193.5, 193.0, 192.3, 171.7,
171.5, 156.6, 156.4, 140.4, 140.3, 131.1, 131.0, 130.8 ,130.7, 128.9
(4C), 128.7 (4C), 107.8(2C), 59.4, 59.2, 11.22, 11.17; HRESIMS
m/z [M + H]+ 229.0839 (calcd for C14H13O3, 229.0859). Anal.
HPLC [tR (min) (content)]: 2.98 (97.7%) from solvent a or 2.95
(98.1%) from solvent b.
2-[(E)-1-Methoxy-3-phenylallylidene]-4,5-dimethylcyclopent-
4-ene-1,3-dione (38). Yield, 60% from methylation of 31, yellow
2-[(E)-3-[4-O-(tert-Butyldimethylsilyl)phenyl]-1-methoxy-
allylidene]-4-methylcyclopent-4-ene-1,3-dione (44). Yield, 85%
1
powder; H NMR (400 MHz, CDCl3) δ 8.04 (1H, d, J ) 16 Hz,
1
H-7), 7.61 (2H, br d), 7.55 (1H), 7.33 (3H, m), 4.18 (3H, s, OMe),
1.99 (6H, br s, Me); 13C NMR (100 MHz, CDCl3) δ 194. 6, 192.2,
167.3, 150.8, 150.3, 141.9, 135.6, 130.1, 128.9 (2C), 128.4 (2C),
121.3, 108.6, 64.5, 9.02 (2C); HRESIMS m/z [M + H]+ 269.1171
(calcd for C17H17O3, 269.1172). Anal. HPLC [tR (min) (content)]:
6.56 (99.5%) from solvent a or 5.72 (99.6%) from solvent b.
2-[(E)-1-Methoxy-3-phenylallylidene]-4-phenylcyclopent-4-
ene-1, 3-dione (39). Yield, 92% from methylation of 32, yellow
from methylation of 37, yellow oil; H NMR (400 MHz, CDCl3,
Z/E-isomers) δ 7.83/7.81 (1H each, d, J ) 16 Hz, H-7), 7.58 (1H
× 2, d, J ) 16 Hz, H-8), 7.52 (2H × 2, d, J ) 8 Hz, H-11, 13),
6.84 (2H × 2, d, J ) 8 Hz, H-10, 14), 6.68/6.66 (1H each, s, H-5),
4.18 (3H × 2, s, OMe), 2.08 (3H × 2, s, Me), 0.98 (9H × 2, s, 3
× Me), 0.22 (6H × 2, s, 2 × Me).
2-[(E)-3-(4-Hydroxyphenyl)-1-methoxyallylidene]-4-methyl-
cyclopent-4-ene-1,3-dione (45). To a solution of 44 (20 mg) in
dry THF (10 mL) tetra-tert-butylammonium fluoride (TBAF) was
added under N2. After being stirred for 3 h at room temperature,
the reaction mixture was extracted with Et2O. The organic layers
were separated, dried (Na2SO4), and evaporated to give the crude
product, which was purified by column chromatography on silica
gel using 30% EtOAc in hexanes to give a pale-orange powder
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powder; H NMR (400 MHz, benzene-d6, Z/E-isomers) δ 8.48/
8.35 (1H each, d, J ) 16 Hz, H-7), 7.84 (2H × 2, m, H-2′, 6′),
7.62 (1H × 2, d, J ) 16 Hz, H-8), 7.45 (3H × 2, m), 7.11 (3H ×
2, m), 7.02 (3H × 2, m), 6.78/6.76 (1H each, s, H-5), 4.0/3.92 (3H
each, s, OMe); 13C NMR (100 MHz, CDCl3, Z/E-isomers) δ 194.0,
193.4, 191.3, 191.1, 170.0, 169.9, 153.0, 152.8, 143.2, 143.0, 138.4,