1410 J. Agric. Food Chem., Vol. 45, No. 4, 1997
Thuring et al.
Sch em e 2. Str a tegy for th e P r ep a r a tion of
Ca r ba -GR24 (1)
indeno[1,2b]furan-2-one (5). A solution of tricyclic lactone 2
(835 mg, 4.80 mmol) in THF (10 mL) was added dropwise to
a cooled (-78 °C) solution of LDA (4.80 mmol) in THF (15 mL)
under N2. The reaction mixture was stirred for 10 min, and
then freshly prepared aldehyde 3b (1.37 g, 4.80 mmol) in THF
(5 mL) was added. Stirring was continued for 1 h at the same
temperature. The reaction mixture was warmed to 0 °C,
stirred for 1 h, and quenched with a saturated solution of
NH4Cl. Then THF was removed in vacuo. Extraction with
ethyl acetate (3 × 20 mL) and washing of the combined organic
extracts with water (2×) and brine followed by drying provided
crude product 5. Purification by flash chromatography (SiO2,
eluent gradient hexane/ethyl acetate, 3:1, 2:1, and then 3:2)
gave seven fractions with different Rf values ranging from 0.17
to 0.062 (eluent hexane/ethyl acetate, 2:1), which all showed
satisfactory 1H-NMR data. Total yield of all collected, pure
fractions: 1.46 g, 66%. From the fast moving fraction (Rf 0.17,
hexane/ethyl acetate, 2:1), pure crystals (106 mg) could be
obtained by crystallization from hexane/ethyl acetate. Mp:
192-195 °C. 1H-NMR (CDCl3, 400 MHz): δ 1.48 (s, 3H, CH3),
1.86 (dd, 1H, 2J ) 13.9 Hz, J ) 9.0 Hz, CH2 D ring), 2.00-
2.11 (m, 2H, CH2), 2.29 (t, 1H, J ) 7.9 Hz, OC(O)CH), 2.55
(dd, 1H, J ) 5.4 Hz, 2J ) 13.9 Hz, CH2 D ring), 2.92 (d, 1H, 2J
standard). Both instruments were from Brucker, Wissem-
bourg, France. All coupling constants are given as J in hertz,
3
unless indicated otherwise. For mass spectra, a double-
focusing VG7070E mass spectrometer from VG Analytical,
Manchester, U.K., was used. GC-MS spectra were run on a
Varian Saturn 2 GC-MS ion-trap system fromVarian Neder-
land BV, Houten, The Netherlands. Separation was carried
out on a fused-silica capillary column (DB-5, 30 m × 0.25 mm).
Helium was used as the carrier gas, and electron impact (EI)
was used as the ionization mode. GLC was conducted with a
Hewlett-Packard HP 5890 gas chromatograph, from Hewlett-
Packard Nederland, using a capillary cross-linked methyl
silicone gum column of 25 m length, 0.32 mm i.d., and 0.17
µm film thickness and nitrogen (2 mL/min, 0.5 atm) as the
carrier gas. Melting points were measured with a Reichert
Thermopan, Vienna, Austria, microscope and are uncorrected.
Elemental analyses were performed at the Department of
Microanalysis of this laboratory.
) 16.4 Hz, CH2 B ring), 3.17 (ddd, 1H, J ) 7.9, 7.7, 7.6 Hz,
2
CH BC rings), 3.33 (dd, 1H, J ) 7.6 Hz, J ) 16.4 Hz, CH2
B
ring), 3.66 (s, 1H, exchanges in the presence of D2O, OH), 4.18
(m, 1H, CHOH), 4.96 (m, 1H, CH D ring), 5.94 (d, 1H, J ) 7.7
Hz, PhCHO), 7.27-7.49 (m, 8H, arom H). MS (CI, m/ z,
relative intensity): 459, 461 ([M]++1, 0.23, 0.05), 441, 443
(0.35, 0.13), 284, 286 (1.74, 0.80), 174 (13.2), 144, 146 (36.6,
14.2), 129 (37.6), 41 (100). Anal. Calcd for C24H23ClO5S: C,
62.81; H, 5.05; S, 6.99. Found: C, 62.88; H, 4.98; S, 6.68.
3-{2-[4-[(4-Chlorophenyl)sulfanyl]-4-methyl-5-oxotetrahydro-
furan-2-yl]ethylidene}-3,3a,4,8b-tetrahydro-2H-indeno[1,2-b]fu-
ran-2-one [(Z-6) via the Mesylate of 5. Typical procedure for
the mesylation of 5: To a solution of pure aldol 5 (Rf 0.17,
eluent hexane/ethyl acetate, 2:1) (50.1 mg, 0.11 mmol) in
CH2Cl2 (3 mL) were added triethylamine (18.2 µL, 0.13 mmol)
and then mesyl chloride (10.1 µL, 0.13 mmol) at 0 °C. The
solution was stirred for 18 h before quenching with a saturated
solution of NaHCO3. The mixture was extracted with CH2Cl2
(2 × 10 mL), and the combined organic layers were washed
with water (2 × 5 mL). Drying and evaporation of the solvent
in vacuo afforded 46.0 mg (78%) of the desired mesylate, which
was sufficiently pure for the next elimination reaction. 1H-
NMR (CDCl3, 100 MHz): δ 1.41 (s, 3H, CH3), 1.81-3.48 (m,
7H), 3.08 (s, 3H, CH3 mesyl), 4.69 (m, 1H, CH D ring), 5.22
(dt, 1H, J ) 3.3, 9.2 Hz, CHOMs), 5.86 (d, 1H, J ) 7.6 Hz,
PhCHO), 7.34 (m, 8H, arom H). MS (CI, m/ z, relative
intensity): 536, 538 ([M]+, 0.51, 0.21), 440, 442 (2.38, 1.28),
297 (1.16), 144, 146 (19.8, 10.2), 97 (8.15), 41 (100).
Solvents were dried using the following methods: Dichlo-
romethane was distilled from P2O5. Diethyl ether was distilled
from NaH. Hexane was distilled from CaH2. Tetrahydrofuran
was distilled from lithium aluminum hydride just before use.
All other solvents were of analytical grade. Thin layer
chromatography (TLC) was carried out on Merck, Darmstadt,
Germany, precoated silica gel 60 F254 plates (0.25 mm), using
the eluents indicated. Spots were visualized with UV light or
by using a molybdate spray. “Flash” chromatography was
carried out at a pressure of ca. 1.5 bar, using Merck Kieselgel
60H. Column chromatography at atmospheric pressure was
carried out using Merck Kieselgel 60.
3,3a,4,8b-Tetrahydroindeno[1,2-b]furan-2-one (2) was pre-
pared following a previously reported synthesis (Mangnus et
al., 1992b).
{4-[(4-Chlorophenyl)sulfanyl]-4-methyl-5-oxotetrahydrofuran-
2-yl}acetaldehyde (3b). Precursor 4 was prepared similarly
to 5-(2,2-diethoxyethyl)-3-methyl-3-(phenylthio)dihydrofuran-
2-one as described by Kishimba and Zwanenburg (1994). Yield
after chromatography (SiO2, hexane/ethyl acetate, 3:1): 65%
as a yellow oil. 1H-NMR (CDCl3, 100 MHz): δ 1.22 (2t, 6H, J
) 7.5 Hz, (OCH2CH3)2), 1.47, 1.52 (2s, 3H, CH3), 1.79-2.21
(m, 3H, CH2CH(OEt)2, CH2), 2.35-2.60 (m, 1H, CH2), 3.58 (m,
4H, (OCH2CH3)2), 4.63 (m, 2H, CH), 7.28-7.57 (m, 4H, arom
H), GC-MS (EI, m/ z, relative intensity): 358, 360 ([M]+, 4.1,
1.9), 313, 315 (5.4, 2.1), 215 (8.4), 241, 243 (3.0, 1.4), 169 (23.6),
143, 145 (13.7, 6.1), 125 (11.8), 103 (100), 75 (66).
A suspension of 4 (2.5 g, 7.0 mmol) in 0.5 N HCl (25 mL)
was heated under reflux for 45 min. The cooled reaction
mixture was extracted with CH2Cl2 (3 × 25 mL), and the
organic extracts were washed with water (2 × 10 mL) and
brine. Drying of the organic phase and evaporation of the
solvent in vacuo gave 3b (1.78 g, 90%) as an orange oil, which
was almost pure. Purification by chromatography (Florisil,
diethyl ether) afforded pure 3b (1.21 g, 61%). Because of its
instability, 3b was characterized only by 1H-NMR and used
immediately for further reactions. 1H-NMR (CDCl3, 100
MHz): δ 1.47, 1.51 (2s, 3H, CH3), 1.89-2.97 (m, 4H, CH2), 5.03
(m, 1H, CH), 7.15-7.54 (m, 4H, arom H), 9.70, 9.76 (2s, 1H,
HCdO). Ratio of diastereomers: 2:1.
The crude mesylate (46.0 mg, 0.09 mmol) was treated with
DBU (16.7 mg, 0.11 mmol) in CH2Cl2 (2 mL) at 0 °C. After 2
h of stirring at the same temperature, the solution was
quenched with a saturated solution of NaHCO3 and extracted
with CH2Cl2 (2 × 10 mL). The combined organic layers were
washed with water (2 × 5 mL) and dried. Removal of the
solvent in vacuo gave almost pure product Z-6, which was
purified by chromatography (SiO2, hexane/ethyl acetate, 2:1)
to give 35 mg, 72% (based on starting aldol 5), of (Z)-6 as a
white solid. 1H-NMR (CDCl3, 100 MHz): δ 1.34 (s, 3H, CH3),
1.92 (dd, 1H, J ) 10.1 Hz, 2J ) 14.1 Hz, CH2 D ring), 2.38
(dd, 1H, J ) 5.5 Hz, 2J ) 14.1 Hz, CH2 D-ring), 2.53-3.57 (m,
4H, 2CH2), 3.78 (m, 1H, CH BC rings), 4.50 (m, 1H, CH D
ring), 5.86 (d, 1H, J ) 7.6 Hz, PhCHO), 6.36 (ddd, 1H, J )
6.9, 8.3 Hz, 4J ) 2.3 Hz, )CH), 7.19 (m, 8H, arom H). MS
(EI, m/ z, relative intensity): 440, 442 ([M]+, 65.6, 26.9), 296
(7.2), 279 (35.2), 225 (34.6), 143, 145 (92.0, 20.7), 109 (43.3),
41 (100). HRMS/EI: m/ z calcd for C24H2135ClO4S 440.0849,
found 440.0849.
3-{2-[4-[(4-Chlorophenyl)sulfanyl]-4-methyl-5-oxotetrahydro-
furan-2-yl]ethylidene}-3,3a,4,8b-tetrahydro-2H-indeno[1,2-b]fu-
ran-2-one [(E)-6]. Typical procedure starting from pure aldol
5 (Rf 0.17, eluent hexane/ethyl acetate, 2:1): To a solution of
3-{2-[4-[(4-Chlorophenyl)sulfanyl]-4-methyl-5-oxotetrahydro-
fu r a n -2-yl]-1-h yd r oxyet h yl}-3,3a ,4,8b-t et r a h yd r o-2H -