argon atmosphere (in a sealed tube if necessary). The reaction
mixture was stirred until starting materials had disappeared on
a TLC analysis, and then evaporated to dryness. The residue was
purified by silica gel column chromatography with CHCl3/MeOH
solvent system containing 0.1% Et3N to give the Diels–Alder
adduct.
NaCl, dried over Na2SO4, and filtered. After evaporation, to a
solution of the residue in MeOH (7.9 mL) was added 10% Pd/C
(40.2 mg, 0.378 mmol) under argon atmosphere. The atmosphere
was displaced with hydrogen, and then the reaction mixture was
stirred for 30 min at rt. After filtration with Celite, the filtrate was
evaporated to give 24 (160 mg, 0.709 mmol, 90%). The resulting
24 was carried on to the next step without further purification
because 24 was pure enough and highly polar; dH (CDCl3) 2.61
(1H, dt, J = 12.5, 6.3 Hz), 2.46 (1H, dd, J = 19.3, 8.8 Hz), 2.32
(1H, dt, J = 12.7, 6.3 Hz), 2.19 (1H, dt, J = 19.3, 9.9 Hz), 1.98–1.91
(2H, m), 1.82–1.67 (5H, m), 1.35–1.25 (2H, m), 0.92 (3H, t, J =
7.5 Hz); dC (CDCl3) 220.6, 178.5, 75.2, 46.7, 45.0, 37.0, 35.1, 32.0,
29.1, 28.0, 22.9, 10.9; IR (film) 3461, 2957, 1737, 1439, 1252, 1163,
1032 cm-1; m/z 226.1205 [M + H]+, C12H18O4 requires 226.1205.
rel-(1S,2S,6R,7R)-11-Ethyl-1-hydroxy-8-oxa-tricyclo[5.2.2.02,6]-
undeca-10-ene-3,5,9-trione 19 (from 16 and 18). dH (CD3OD)
5.97 (1H, q, J = 2.0 Hz), 5.22 (1H, s), 5.17 (1H, t, J = 2.0 Hz),
3.34 (1H, s), 3.16 (1H, dd, J = 7.3, 2.0 Hz), 3.02 (1H, d, J = 7.3
Hz), 2.30 (2H, qd, J = 7.3, 2.0 Hz), 1.10 (3H, t, J = 7.3 Hz); dC
(CD3OD) 197.8, 197.8, 174.9, 147.8, 130.0, 109.1, 78.8, 78.2, 51.4,
50.6, 23.4, 11.5; IR (film) 2969, 2523, 1767, 1752, 1653, 1560,
1387, 1297, 1140, 961 cm-1; m/z 237.0774 [M + H]+, C12H12O5
requires 237.0763.
Methyl rel-(1S,2S,4R,6S)-4-ethyl-2-hydroxy-7-oxo-bicyclo-
[4.3.0]nonane-2-carboxylate 25. To a solution of 24 (5.8 mg,
25.6 mmol) in MeOH (0.5 mL) was added TsOH·H2O (3.4 mg,
17.9 mmol). After the reaction mixture was stirred and refluxed for
one day, it was allowed to stand at room temperature. The reaction
was stopped by the addition of aqueous NaHCO3. Then the
organic layer was washed with saturated aqueous NaCl, dried over
Na2SO4, and filtered. After evaporation, the residue was purified
by silica gel column chromatography (n-hexane/acetone = 30/1–
20/1) to give 25 (4.9 mg, 20.6 mmol, 80%) as a colorless oil; dH
(CDCl3) 3.81 (3H, s), 2.60 (1H, dt, J = 13.2, 6.2 Hz), 2.43 (1H, dd,
J = 19.0, 8.4 Hz), 2.28 (1H, dt, J = 12.8, 6.2 Hz), 2.16 (1H, dt, J =
19.0, 10.0 Hz), 1.89 (1H, m), 1.81–1.61 (5H, m), 1.36–1.23 (2H,
m), 0.91 (3H, t, J = 7.4 Hz); dC (CDCl3) 219.0, 175.8, 75.2, 52.4,
46.6, 45.8, 36.9, 35.2, 32.0, 29.2, 28.1, 22.8, 10.9; IR (film) 3461,
2957, 1737, 1439, 1252, 1163, 1032 cm-1; m/z 241.1452 [M + H]+,
C13H21O4 requires 241.1440.
Synthesis of coronafacic acid
rel -(1S,2S,6R,7R)-3-Chloro-11-ethyl-1-hydroxy-8-oxa-tri-
cyclo[5.2.2.02,6]undeca-3,10-diene-5,9-dione 22. To a solution of
19 (104 mg, 0.308 mmol) in CH2Cl2 (3.0 mL) was added triphos-
gene (54.3 mg, 0.183 mmol) at 0 ◦C under argon atmosphere.
The reaction mixture was stirred for 10 min, and then DIPEA
(39.8 mg, 0.308 mmol) was slowly added. Then the reaction
mixture was gradually warmed to room temperature and stirred
for overnight. The reaction mixture was evaporated to dryness,
and the residue was purified by silica gel column chromatography
(n-hexane/acetone = 16/1–1/1) to give 22 (24.1 mg, 94.6 mmol,
31%) as a pale yellow oil and recovered 19 (29.6 mg, 87.7 mmol,
28%); dH (CDCl3) 6.35 (1H, d, J = 1.0 Hz), 6.01 (1H, q, J = 1.9
Hz), 5.22 (1H, t, J = 1.9 Hz), 3.77 (1H, br s), 3.44 (1H, dd, J =
7.3, 1.0 Hz), 2.98 (1H, dd, J = 7.3, 1.9 Hz), 2.26 (1H, m), 1.06
(3H, t, J = 7.3 Hz); 1dC (CDCl3) 198.9, 172.7, 169.9, 145.9, 135.4,
128.1, 78.0, 77.9, 53.5, 51.3, 24.4, 10.9; m/z 255.0414 [M + H]+,
C12H11ClO4 requires 255.0424.
Methyl rel-(1S,4R,6S)-4-ethyl-7-oxo-bicyclo[4.3.0]non-2-ene-2-
carboxylate 26. To a solution of 25 (98.9 mg, 0.412 mmol) in
pyridine (4.0 mL) was added phosphorus oxychloride (1.32 g,
8.58 mmol) at 0 ◦C under argon atmosphere. The reaction mixture
was gradually warmed to room temperature with overnight
stirring. The reaction mixture was quenched with slow addition of
cold H2O, and then extracted with Et2O (4 ¥ 50 mL). The resulting
organic layer was washed with saturated aqueous NaCl, dried over
Na2SO4, and filtered. After evaporation, the residue was purified
by silica gel column chromatography (n-hexane/acetone = 60/1–
16/1) to give 26 (76.2 mg, 0343 mmol, 83%) as a colorless oil. All
spectral data of 26 were identical to those of reported one.11
rel -(1S,2S,6R,7S,11S)-11-Ethyl-1-hydroxy-8-oxa-tricyclo-
[5.2.2.02,6]undecane-5,9-dione 23. To a solution of 22 (6.00 mg,
23.6 mmol) in toluene (1.0 mL) under argon atmosphere was added
10% Pd/C (7.70 mg, 7.24 mmol). The atmosphere was displaced
with hydrogen, and the reaction mixture was stirred for 1 day at rt.
After filtration with Celite, the filtrate was evaporated to dryness.
The residue was purified by silica gel column chromatography
(n-hexane/EtOAc = 1/1) to give a 7:1 mixture of two stereoiso-
mers of 23 (3.90 mg, 17.4 mmol, 74%, 11S*:11R* = 7:1) as a pale
yellow oil; dH (CDCl3) 4.77 (1H, s), 3.88 (1H, br s), 2.86 (1H, m),
2.79 (1H, dd, J = 7.8, 1.9 Hz), 2.71 (1H, d, J = 7.8 Hz), 2.27–2.09
(4H, m), 1.87–1.73 (2H, m), 1.47–1.25 (3H, m), 0.87 (3H, t, J =
7.3 Hz); dC (CDCl3) 216.3, 176.7, 78.2, 72.6, 50.6, 41.6, 39.1, 37.3,
37.0, 26.3, 21.7, 11.0; IR (film) 3452, 1741, 1460, 1407, 1370, 1312,
1264, 1219, 1009, 960, 754 cm-1; m/z 225.1098 [M + H]+, C12H17O4
requires 225.1121.
Coronafacic acid ( )-2 (from 26). A suspension of 26 (69.6 mg,
0.313 mmol) in 3 M aqueous HCl (3.1 mL) was refluxed for 10 h.
After the reaction mixture was quenched with H2O, the mixture
was extracted with EtOAc (4 ¥ 10 mL). The resulting organic layer
was washed with saturated aqueous NaCl, dried over Na2SO4,
and filtered. After evaporation, coronafacic acid ( )-2 (64.6 mg,
0.310 mmol, 99%) was obtained as a colorless crystalline solid. All
spectral data of ( )-2 were identical to those reported.11
rel -(1S,2S,4R,6S)-4-Ethyl-2-hydroxy-7-oxo-bicyclo[4.3.0]-
nonane-2-carboxylic acid 24. To a solution of 23 (176 mg,
0.785 mmol) in MeOH (7.9 mL) was added NaOMe (42.4 mg,
Coronafacic acid ( )-2 (from 24). To a suspension of 24
(2.3 mg, 10.2 mmol) in H2O (0.5 mL) was added 98% H2SO4
(0.5 mL). After being refluxed for 3 h, the reaction mixture was
quenched with H2O. The mixture was extracted with EtOAc (4 ¥
5 mL) and the resulting organic layer was washed with saturated
aqueous NaCl, dried over Na2SO4, and filtered. After evaporation,
◦
7.52 mmol) at 0 C under argon atmosphere. After the reaction
mixture was stirred for 10 min, the reaction mixture was quenched
with 5% aqueous KHSO4. The mixture was extracted with EtOAc
(3 ¥ 50 mL). The organic layer was washed with saturated aqueous
3070 | Org. Biomol. Chem., 2009, 7, 3065–3073
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The Royal Society of Chemistry 2009
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