Synthesis and cytotoxicity of novel benzofuran neolignan derivatives

Article abstract of DOI:10.3184/030823410X12709997864719

A series of 10 related benzofuran neolignan derivatives were obtained by utilising a biomimetic reaction sequence involving oxidative dimerisation of methyl ferulate, followed by derivatisation reactions. The structures of the new compounds were confirmed by ¹H NMR, elemental analysis, MS and IR. All compounds were evaluated for their cytotoxic potential against five human cancer cell lines (HL-60, SMMC-7721, A-549, SK-BR-3 and PAN-1) by the standard MTT method. The results showed that most of them exhibit potent cytotoxicity.

Full text of DOI:10.3184/030823410X12709997864719

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 233
APRIL, 233–235
Synthesis and cytotoxicity of novel benzofuran neolignan derivatives
Hua-Fang Fan, Ying-Mei Ren, Xiu-Ling Wu and Qiu-An Wang*
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha
410082, P. R. China
A series of 10 related benzofuran neolignan derivatives were obtained by utilising a biomimetic reaction sequence
involving oxidative dimerisation of methyl ferulate, followed by derivatisation reactions. The structures of the
1
new compounds were confirmed by H NMR, elemental analysis, MS and IR. All compounds were evaluated for
their cytotoxic potential against five human cancer cell lines (HL-60, SMMC-7721, A-549, SK-BR-3 and PAN-1) by the
standard MTT method. The results showed that most of them exhibit potent cytotoxicity.
Keywords: benzofuran neolignans, synthesis, cytotoxicity
The benzofuran system, as a significant pharmacophore, is
contained in numerous compounds which can be isolated
from natural sources as well as in synthetic products. Multiple
substituted benzofuran neolignans have received increasing
attention due to their excellent biological activities, such as
antitumour, antifungal, antimicrobial, antivirus and adenosine
aluminium agonist properties.1,2 Despite many recent reports
on benzofuran neolignans and related compounds,3–7 the full
potential of this class of compounds has yet to be realised in
terms of both more new molecules and diverse biological
activity as drugs.
The present investigation was stimulated by the discovery
of some synthetic dihydrobenzofuran neolignans and related
benzofuran compounds, which showed potent cytotoxic
activity against the human cancer cell lines (HL-60, K-562,
NCI-H522, HCT-15, SF-539, M14, OVCAR-3, VO-31, DV-
145, MB-435, MDA-N and BT-549).8 The cytotoxicity of these
benzofuran neolignans is strongly dependent on the substitu-
tion pattern.Alterations in the chemical structure of benzofuran
have significant effects on their biological properties.
With the aim of developing new antitumour-active com-
pounds and investigating structure–activity relationships of
benzofuran neolignans derivatives 4–13, the present study
reports the synthesis and cytotoxicity bioassays of a series
among which, compounds 5 (herpetol9), 6, 8–13, were first
synthesised.
attention to modification of benzofuran neolignans by the
prenyl or farnesyl moiety. Compounds 3, 5 and 6, were reacted
with commercially available prenyl bromide or trans, trans-
farnesyl bromide in the presence of anhydrous potassium car-
bonate and anhydrous acetone at ambient temperature, to give
five O-prenyl or O-farnesyl substituted benzofuran neolignans
derivatives 9–13.
The 10 benzofuran neolignans derivatives 4–13 were tested
for cytotoxic activity against myeloid leukaemia (HL-60), liver
carcinoma (SMMC-7721), lung carcinoma (A-549), breast
tumour cells (SK-BR-3) and pancreatic cancer (PANC-1) cell
line by standard MTT method. The results showed that most of
them have good activity. IC50 values (µg/mL) of synthetic novel
benzofuran neolignans derivatives on five human caner cell
lines were plotted in Table 1. Compounds 5, 6 and 12 exhibited
potent cytotoxicity against the PANC-1 cancer cell line with
IC50 values of 10.83, 12.32 and 19.84 µg/mL respectively.
Compounds 7 and 12 showed cytotoxicity against cancer cell
lineA-549 with IC50values of 7.2 and 3.65 µg/mL. Compound
12 showed cytotoxicity against cancer cell line SMMC-7721
with IC50 values of 7.61 µg/mL. Biological activities of all the
compounds mentioned above are similar or even improved
compared with the positive control, cisplatin (DPP).
Experimental
Melting points were measured on a XRC-I apparatus and were uncor-
rected. IR spectra were recorded on a Bruker Tensor-27 spectrometer,
1H NMR spectra were recorded on a Bruker AM-400 instrument,
using tetramethylsilane as an internal standard, chemical shifts (δ) in
ppm, coupling constants (J) in Hz, Mass spectra were determined
with ZAB-HS spectrometer by the EI or FAB method. Elemental
analyses were carried out on a Perkin-Elmer 240B microanalyser.
All solvents were dried by standard procedures. Methyl ferulate was
prepared from vanillin and malonic acid by the reported procedure13.
2-(3-methoxy-4-acetyloxyphenyl)-3-methoxycarbonyl-5-(3-methoxy-
carbonylvinyl)-7-methoxy-2,3-dihydrobenzo[b]furan (1)14, 2-(3-
methoxy-4-acetyloxyphenyl)-3-methoxycarbonyl-5-(3-methoxycar-
bonylvinyl)-7-methoxybenzo[b]furan (2)14, 2-(3-methoxy-4-hydroxy-
phenyl)-3-methoxycarbonyl-5-(3-methoxycarbonylvinyl)-7-methoxy-
benzo[b]furan(3)14 and2-(3-methoxy-4-acetyloxyphenyl)-3-methoxy-
carbonyl-5-(3-methoxycarbonylethyl)-7-methoxybenzo[b]furan (4)8
were prepared according to previous methods.
Results and discussion
The title compounds were synthesised according to the
route shown in Scheme 1. With methyl ferulate as the starting
material, Ag2O-catalysed biomimetic oxidative coupling was
the crucial step10 in the reaction sequence, which generated its
dimer in 43% yield. The structure of the dimer was found to be
1
the dihydrobenzofuran compound characterised by H NMR
and MS. Acetylation of the dimer with acetic anhydride and
pyridine afforded the compound 1. This was then dehydroge-
nated by 2.3-dichloro-5, 6-dicyanobenzoquinone (DDQ) in 1,
4-dioxane to give the compound 2. Hydrolysis of 2 in the pres-
ence of potassium carbonate and methanol under reflux gave
the compound 3. Compound 4 was obtaineded by catalytic
hydrogenation of the double bond in the side chain of com-
pound 2 in THF, with 5% Pd/C as catalyst. Compounds 2 and
4 were subjected to reduction by lithium aluminium hydride to
afford the corresponding benzofuran neolignan monoalcohol
derivatives 6, 7 and diols 5, 8, respectively.
Prenyl or farnesyl moieties can potentially substitute for
conventional lipids as lipophilic carriers of bioactive mole-
cules. The introduction of a prenyl or farnesyl moiety in bioac-
tive molecules is an important post-translational modification
centre to many cellular processes.11,12 Next, we turned our
Synthesis of herpetol (5) and 2-(3-methoxy-4-hydroxyphenyl-
3-methoxycarbonyl-5-(3-hydroxypropenyl)-7-methoxybenzo [b]furan
(6): To a solution of compound 2 (115 mg, 0.25 mmol) in THF (10 mL)
LiAlH4 (45 mg, 1.19 mmol) was added at 0°C. After stirring at room
temperature for 5 h, the reaction mixture was decomposed with 5%
H2SO4 (5 mL), then water (10 mL) was added. The aqueous solution
was extracted with EtOAc (3 × 15 mL), and the organic layer was
washed with brine (2 × 15 mL), dried over anhydrous mgSO4. The
solvent was removed in a vacuum, the residue was chromatographed
on a silica gel with petroleum ether/ethyl acetate (1:1) to give herpetol
(5) as white solid 57 mg, yield 50.5%, and compound 6 as white solid
23 mg, yield 15.2%.
Herpetol (5): M.p. 167–168°C; 1H NMR (DMSO-d6, 400 MHz): δ
9.49 (s, 1H, 4p-OH), 7.40 (d, J = 2.0 Hz, 1H, H-2p), 7.31 (s, 1H, H-4),
* Correspondent. E-mail: wangqa@hnu.cn

234 JOURNAL OF CHEMICAL RESEARCH 2010
Scheme 1 Synthetic route of benzofuran neolignans derivatives 4–13.
Table 1 IC values (µg/mL) of benzofuran neolignans
1146, 1102, 1056, 994, 886, 859; MS: m/z 356 [M+]. Anal. Calcd
for C20H20O6: C, 67.41; H, 5.66. Found: C, 67.28; H, 5.42%. The
spectral data are in agreement with those reported previously for this
compound.9
derivatives5o0n the human cancer cell lines
Compound HL-60 SMMC-7721 A-549 SK-BR-3 PANC-1
1
1
4
4.03
2.31
2.30
>30
3.88
>30
>30
>30
3.6
23.37
13.49
13.61
>30
18.90
>30
>30
>30
7.61
22.68 >30
>30 11.62
>30
10.83
12.32
>30
>30
>30
>30
>30
6: M.p 169–170°C, H NMR (DMSO-d6, 400 MHz):δ9.77 (s, H,
1
1
5
4p-OH), 7.64 (d, J = 2.0 Hz, H, H-2p), 7.51 (s, H, H-4), 7.45 (dd,
J = 8.0, 2.0 Hz, 1H, H-6p), 7.14 (s, 1H, H-6), 6.92 (d, J = 8.0 Hz, 1H,
H-5p), 6.66 (m, J = 16.0 Hz, 1H, H-8), 6.64 (m, 1H, H-9), 4.89 (t, 1H,
10-OH), 4.16 (m, 2H, H-10), 3.99, 3.88, 3.84 (s, 3H/each, -OCH3).
IR (KBr)cm−1:3540, 3481, 3414, 3017, 2946, 2849, 1712, 1598,
1570, 1511, 1469, 1451, 1424, 1378, 1320, 1276, 1236, 1222, 1148,
1098, 1048, 963, 852, 812, 788, 735, 696, 603. MS: m/z 384 [M+].
Anal. Calcd for C21H 20O7: C, 65.62; H, 5.24. Found: C, 65.33; H,
5.43%.
6
>30
>30
>30
>30
7
8
7.20 >30
9
>30
>30
>30
>30
>30
>30
10
11
12
3.65
>30
9.00
21.93
>30
5.27
19.84
>30
19.84
13
3.09
0.51
22.05
5.87
DDP
(MW300)
Synthesis of 2-(3-methoxy-4-hydroxyphenyl)-3-methoxycarbonyl-
5-(3-hydroxypropyl)-7-methoxy benzo [b] furan (7) and 2-(3-methoxy-
4-hydroxyphenyl)-3-hydroxymethyl-5-(3-hydroxypropyl)-7-methoxy
benzo[b] furan (8): To a solution of compound 4 (542 mg, 1.19 mmol)
in THF (10 mL) was added LiAlH4 (90 mg, 2.38 mmol) at 0°C. After
stirring at room temperature for 12 h, the reaction mixture was
quenched with 5% H2SO4 (160 mL), then water (10 mL) was added.
The aqueous solution was extracted with EtOAc (3 × 20 mL), the organic
layer was washed with brine (2 × 20 mL), dried over anhydrous
7.29 (dd, J = 8.0, 2.0 Hz, 1H, H-6p), 7.03 (s, 1H, H-6), 6.94 (d, J = 8.0 Hz,
1
1
1H, H-5p), 6.64 (d, J = 16.0 Hz, H, H-8), 6.41 (m, H, H-9), 5.28 (t,
J = 5.2 Hz, 1H, 11-OH), 4.88 (t, J = 5.6 Hz, 1H, 10-OH, 4.70 (d,
J = 4.8 Hz, 2H, H-11), 4.16 (m, J = 5.6, 5.2 Hz, 5.2 Hz, 2H, H-10),
3.99, 3.86 (s, 3H/each, -OCH3). IR (KBr) cm−1: 3473, 3455, 3001,
2937, 2852, 1654, 1609, 1514, 1465, 1429, 1377, 1312, 1272, 1221,

JOURNAL OF CHEMICAL RESEARCH 2010 235
MgSO4. The solvent was evaporated and purified by silica gel chro-
matography with petroleum ether/ethyl acetate (1:1) as eluent to
afford compound 7 as white solid 140 mg, yield: 33%; and compound
8 as white solid 200 mg, yield: 44%.
1.61, 1.60, 1.54 (s, 3H/each, –CH3). IR (KBr) cm−1: 3376, 2965, 2920,
1670, 1599, 1514, 1479, 1381, 1344, 1310, 1254, 1221, 1189, 1148,
1091, 1038, 993, 965, 854, 802, 778, 702; MS (FAB+): m/z 559
(M+1)+. Anal. Calcd for C35H42O6: C, 75.24; H, 7.58. Found: C, 75.51;
H, 7.42%.
7: M.p. 122–123°C; 1HNMR (DMSO3-d6, 400 MHz): δ 9.47 (s, 1H,
1
1
4p-OH), 7.39 (d, J = 1.2 Hz, H, H-2p), 7.28 (dd, J = 8.0, 1.2 Hz, H,
Synthesis of 2-(3-methoxy-4-O-prenylphenyl)-3-methoxy carbonyl-
5-(3-hydroxypropenyl)-7-methoxybenzo [b] furan (13): Prepared from
compound 6 and prenyl bromide as described for the preparation of
compound 9 from compound 3 and prenyl bromide. White solid,
yield: 26%; m. p. 104–105°C; 1H NMR (CDCl3, 400 MHz): δ 7.69 (d,
H-6p), 7.10 (s, 1H, H-4), 6.91 (d, J = 8.0 Hz, 1H, H-5p), 6.76 (s, 1H, H-
1
6), 5.25 (t, J = 4.8 Hz, H, 11-OH), 4.68 (d, J = 4.8 Hz, 2H, H-11),
4.52 (s, 1H, 10-OH), 3.95, 3.86 (s, 3H/each, OCH3), 3.48–3.43 (m, 2H,
H-10), 2.70 (t, J = 8.0 Hz, 2H, H-8), 1.83–1.76 (m, 2H, H-9). MS:
m/z 358 [M+]. Anal. Calcd for C20H22O6: C, 67.03; H, 6.19. Found: C,
66.62; H, 5.85%. The spectral data are in agreement with those
reported previously for this compound.15
1
1
J = 2.0 Hz, H, H-2p), 7.67 (dd, J = 8.4, 2.4 Hz, H, H-6p), 7.60 (d,
1
1
J = 1.2 Hz, H, H-4), 6.963 (d, J = 8.4 Hz, H, H-5p), 6.92 (d, J =
1
1
1
1.2 Hz, H, H-6), 6.73 (d, J = 16.0 Hz, H, H-8), 6.39 (m, H, H-9),
1
1
8: M.p. 119–120°C, H NMR (CDCl3, 400 MHz): δ 7.68 (d, J =
5.54 (m, H, H-2q), 4.67 (d, J = 6.4 Hz, 2H, H-1q), 4.37 (m, 2H, H-
1
1
2.0 Hz, H, H-2p), 7.60 (dd, J = 8.0, 2.0 Hz, H, H-6p), 7.42 (d, J =
10), 4.03, 3.96, 3.95 (s, 3H/each, –OCH3), 1.79, 1.76 (s, 3H/each,
–CH3). IR (KBr) cm−1: 3429, 2939, 2858, 2598, 2031, 1712, 1599,
1509, 1468, 1383, 1314, 1262, 1181, 1143, 1093, 1048, 990, 887, 861,
790, 738. MS (FAB+): m/z 453 (M+1)+. Anal. Calcd for C26H28O7: C,
69.01; H, 6.24. Found: C, 69.29; H, 6.38%.
1
1
0.8 Hz, H, H-4), 6.99 (d, J = 8.0 Hz, H, H-5p), 6.68 (d, J = 0.8 Hz,
1H, H-6), 6.46(s, H, 4p-OH), 3.98, 3.93, 3.92 (s, 3H/each,-OCH3),
1
3.72, 2.80 (m, 2H, H-10), 2.70 (t, J = 8.0 Hz, 2H, H-8), 1.83–1.76 (m,
2H, H-9), IR (KBr) cm−1: 3454, 3311, 3086, 2950, 2840, 1710, 1597,
1521, 1477, 1434, 1287, 1242, 1138, 1092, 1046, 877, 821. MS: m/z
384 [M+]. Anal. Calcd for C21H 22O7: C, 65.28; H, 5.74. Found: C,
64.91; H, 5.52%.
Assay for cytotoxic activity
The cytotoxic assay was performed by using the (4, 5-dimethylthia-
zol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay method,
cisplatin (DDP, MW300) as a positive control. Five different human
cancer cell lines, myeloid leukaemia (HL-60), liver carcinoma
(SMMC-7721), lung carcinoma (A-549), breast tumour cell (SK-BR-
3) and pancreatic cancer (PANC-1), were cultured on DMEM or
RPMI-1640 medium supplemented with foetal bovine serum (10%).
A suspension of the cells was added to each well (1 × 104 – 2 × 104
cells/well, 100 µL) of 96-microwell plate and incubated for 12 h.
Test compounds were dissolved in DMSO at various concentrations
(30, 10, 1 and 0.1 µg/mL) and 10 µL of the test solutions or DMSO
(control) was added to each well. The plate was incubated at 37°C for
48 h. After termination of the cell culture by adding 5% MTT in PBS
(20 µL) to each well, the plate was kept in the incubator for 4 h. To
each well was added 100 µL of 20% SDS, the formazan crystals were
dissolved and the plate was read on a microplate reader (Bio-Rad 680)
at 595 nm. A dose–response curve was plotted for each compound,
and the half maximal inhibitory concentration (IC50) for cancer cell
lines was recorded.
Synthesis of 2-(3-methoxy-4-O-prenylphenyl)-3-methoxycarbonyl-
5-(3-hydroxypropenyl)-7-methoxy benzo [b] furan (9): To a mixture
of compound 3 (50 mg, 0.12 mmol) and anhydrous K2CO (165 mg,
1.2 mmol) in dry acetone, a solution of prenyl bromide 3(0.04 mL,
0.12 mmol) in acetone (2 mL) was added dropwise with stirring. The
reaction was allowed to proceed at room temperature for 3 h, and then
the reaction mixture was filtered and evaporated. The residue was
subjected to chromatography on silica gel with petroleum ether/ethyl
acetate (3:1) as eluent to give compound 9 as a light yellow solid
1
30 mg, yield 52%; m. p. 135–136°C; H NMR (CDCl3, 400 MHz):
δ7.82 (s, 1H, H-4), 7.72 (d, J = 2.0 Hz, 1H, H-2p), 7.70 (dd, J = 8.0 Hz,
1
1
1H, H-5p), 6.47 (d, J = 16.0 Hz, H, H-9), 5.54 (t, J = 6.8 Hz, H,
H-2p), 4.68 (d, J = 6.8 Hz, 2H, H-1p), 4.06, 3.97, 397, 3.84 (s, 3H/
each,-OCH ), 1.69 (s, 3H, –CH ), 1.60 (s, 3H, –CH3). IR (KBr)cm−1:
3092, 29483, 1723, 1912, 1602, 31511, 1478, 1246, 1148, 1088, 1055,
846. MS (FAB+): m/z 483 (M+1)+. Anal. Calcd for C27H28O8: C, 67.49;
H, 5.87. Found: C, 67.62; H, 5.96%.
Synthesis of 2-(3-methoxy-4-O-farnesylphenyl)-3-methoxy carbonyl-
5-(3-hydroxypropenyl)-7-methoxybenzo [b] furan (10): Prepared from
compound 3 and trans, trans-farnesyl bromide by the same procedure
as for 9 synthesis.Yield: 52%; White solid; m. p. 100–101°C; 1HNMR
(CDCl3, 400 MHz): δ 7.82 (d, J = 16.0 Hz, 1H, H-8), 7.80 (s, 1H, H-4),
This work was supported by the Personal Training Funds in
National Basic Science of China (J0830415).
1
1
7.73 (d, J = 1.6 Hz, H, H-2), 7.70 (dd, J = 8.41, 1.6 Hz, H, H-6p),
7.02 (s, 1H, H-6), 6.97 (d, J = 8.4 Hz, 1H, H-5p), 6.47 (d, J = 16.0 Hz,
1H, H-9), 5.54 (t, 1H, H-2p), 5.13–5.06 (m, 2H, H-6q, H-10q), 4.67 (d,
J = 16.0 Hz, 2H, H-1q), 4.05 (s, 3H, 11-OCH ), 3.97 (s, 6H, 10, 3p-
OCH3), 3.84 (s, 3H, 7-OCH3), 2.15–1.94 (m, 83H,-CH2-4q, 5q, 8q, 9q).
IR (KBr)cm−1: 3093, 2948, 2920, 1716, 1632, 1601, 1510, 1475, 1247,
1232, 1149, 1084, 1039, 845, 785; MS (FAB+): m/z 615 (M+1)+. Anal.
Calcd for C H O : C, 72.29; H, 6.89. Found: C, 72.55; H, 6.68%.
Synthesis37of422-8(3-methoxy-4-O-prenylphenyl)-3-hydroxymethyl-5-
(3-hydroxypropenyl)-7-methoxy benzo[b] furan (11): Prepared from
herpetol (5) and prenyl bromide as described for the preparation of
compound 9 from compound 3 and prenyl bromide. White solid,
yield: 23%; m.p. 98–99°C; 1H NMR (DMSO-d6, 400 MHz): δ 7.41 (d,
J = 5.0 Hz, 1H, H-2p), 7.38 (dd, J = 8.4, 2.0 Hz, 1H, H-6p), 7.32 (s, 1H,
Received 3 March 2010; accepted 2 April 2010
Paper 101033; doi:10.3184/030823410X12709997864719
Published online: 30 April 2010
References
1
2
Y.H. Kuo and C.H. Wu, J. Nat. Prod., 1996, 59, 625.
Z. Yang, H.B. Liu, C.M. Lee, H.M. Chang and H.N.C. Wong, J. Org.
Chem., 1992, 57, 7248.
3
4
5
C.L. Kao and J.W. Chern, J. Org. Chem., 2002, 67, 6772.
S.Y. Lin, C.L. Chen and Y.J. Lee, J. Org. Chem., 2003, 68, 2968.
Q.A. Wang, Z.J. Zhang, C.X. Zhang and H.F. Fan, Chin, J. Org. Chem.,
2008, 28, 1605.
6
J.S. Bose, V. Gangan, R. Prakash, S.K. Jain and S.K. Manna, J. Med.
Chem., 2009, 52, 3184.
1
1
H-4), 7.14 (d, J = 8.8 Hz, H, H-5p), 7.05 (s, H, H-6), 6.64 (d, J =
1
1
1
16.0 Hz, H, H-8), 6.41 (m, H, H-9), 5.47 (t, J = 6.8 Hz, H, H-2q),
5.3 (t, J = 5.2 Hz, 1H, 11-OH), 4.88 (t, J = 5.6 Hz, 1H, 10-OH), 4.70
(d, J = 4.8 Hz, 2H, H-11), 4.59 (d, J = 6.4 Hz, 2H, H-1p), 4.15 (dd,
J = 5.6, 5.2 Hz, 2H, H-10), 3.99, 3.84 (s, 3H/each,-OCH3), 1.77, 1.73
(s, 3H/each,-CH3). MS (FAB+): m/z 425 (M+1)+, Anal. Calcd for
C25H28O6: C, 70.7; H, 6.65. Found: C, 70.49; H, 6.42%.
7
8
S.-i. Wada, T. Hitomi and R. Tanaka, Helv. Chim. Acta, 2009, 92, 1610.
S.V. Miert, S.V. Dyck, T.J. Schmidt, R. Brun, A. Vlietinck, G. Lemière and
L. Pieters, Bioorg. Med. Chem., 2005, 13, 661.
9
M. Kaouadji and J. Favre-Bonvin, Z. Naturforsch., C: Biosci., 1984, 39C,
307.
10 D.L.A. Rakotondramanana, M. Delomenède, M. Baltas, H. Duran, F.
Bedos-Belval, P. Rasoanaivo, A. Negre-Salvayre and H. Gornitzka, Bioorg.
Med. Chem., 2007, 15, 6018.
11 F. Epifano, M. Curini, S. Genovese, M. Blaskovich, A. Hamilton and S.M.
Sebti, Bioorg. Med. Chem., 2007, 17, 2639.
12 M.K. Clark, S.A. Scott, J. Wojtkowiak, R. Chirco, P. Mathieu, J.J. Reiners,
R.R. Mattingly, R.F. Borch and R.A. Gibbs, J. Med. Chem., 2007, 50,
3274.
Synthesis of 2-(3-methoxy-4-O-farnesylphenyl)-3-hydroxylmethyl-
5-(3-hydroxyl-propenyl)-7-methoxy benzo[b] furan (12): Prepared
from herpetol (5) and trans, trans-farnesyl bromide as described for
the preparation of compound 9 from compound 3 and prenyl bromide.
Light yellow solid, yield: 46%; m. p. 68–69°C; 1H NMR (DMSO-d6,
400 MHz): δ 7.41 (d, J = 2.0 Hz, 1H, H-2p), 7.36 (m, 1H, H-6p), 7.31
1
1
1
(s, H, H-4), 7.12 (d, J = 8.4 Hz, H, H-5p), 7.04 (d, J = 1.2 Hz, H,
H-6), 6.64 (d, J = 16.4 Hz, 1H, H-8), 6.41 (m, 1H, H-9), 5.45 (t,
J = 6.0, 1H, H-2q), 5.30 (t, J = 5.2 Hz, 1H, OH-11), 5.07 (m, 2H, H-6q,
10q), 4.87 (t, J = 5.2 Hz, 1H, OH-10), 4.69 (d, J = 5.2 Hz, 2H, H-11),
4.61 (d, J = 6.8 Hz, 2H, H-1q),4.15 (dd, J = 5.2 Hz, 2H, H-10), 3.98,
3.84 (s, 3H/each,-OCH3), 2.10-1.89 (m, 8H, H-4q, 5q, 8q, 9q), 1.72,
13 S.K. Talapatra, S.K. Mukhopadhyay and B. Talapatra, Phytochemistry,
1975, 14, 836.
14 S. Maeda, H. Masuda and T. Tokoroyama, Chem. Pharm. Bull., 1994, 42,
2500.
15 M. Kaouadji, J. Favre-Bonvin and A. M. Mariotte, Phytochemistry, 1978,
17, 2134.

Copyright of Journal of Chemical Research is the property of Science Reviews 2000 Ltd. and its content may
not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written
permission. However, users may print, download, or email articles for individual use.