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F. Saliu et al. / Tetrahedron Letters 52 (2011) 3856–3860
extracted with ethyl acetate (4 ꢁ 20 mL). The combined organic extracts were
washed with 10% aqueous NaHCO3 (25 mL), then with water saturated with
NaCl (25 mL), and dried over Na2SO4. The solvent was evaporated under
reduced pressure, and the residue was chromatographed on a silica gel flash
column (Merck silica gel 60, 0.040–0.063 mm, 230–400 mesh ASTM) with
hexane–ethyl acetate (gradient mode from 4:1 to 1:1).
Compound 7: Methyl(E-3-[2-(4-hydroxy-3,5-dimethoxy-phenyl)-7-methoxy-3-
methoxycarbonyl-2,3-dihydro-1-benzofuran-5-yl]propen-2-enoate. Amorphous
yellow–brown powder. UV kmax (MeOH) nm: 206, 329. 1H NMR (CDCl3, dH):
7.64 (1H, d, J = 15.10 Hz); 7.08 (1H, s); 6.98 (1H, s); 6.63 (2H, s); 6.32(1H, d,
J = 15.10 Hz); 6.11(1H, d, J = 7.08 Hz); 5.61 (1H, s,); 4.32 (1H, d, J = 7.10 Hz);
3.91 (6H, s); 3.87 (3H,s) 3.81 (3H, s); 3.69 (3H, s).13C NMR: 172.8, 168.1, 145.3,
143.2, 139.8, 132.5, 127.6, 119.5, 118.1, 114.9, 110.4, 104.1, 87.9, 56.8, 56.5,
56.2, 53.6, 52.4. APCI-MS m/z 445.1 0.1 [M+H]+.
Compound 9: Methyl(E-3-[2-(4-hydroxy-3,5-dimethoxy-phenyl)-7-hydroxy-3-
methoxycarbonyl-2,3-dihydro-1-benzofuran-5-yl]propen-2-enoate. Amorphous
yellow–brown powder. UV kmax (MeOH) nm: 210, 325. 1H NMR (CDCl3, dH):
7.62 (1H, d, J = 15.08 Hz); 7.11 (1H, s); 6.89 (1H, s); 6.62 (2H, s,); 6.31 (1H, d,
J = 15.08 Hz); 6.10 (1H, d, J = 7.10 Hz); 5.60 (1H, s); 5.30 (1H, s); 4.34 (1H, d,
J = 7.10 Hz); 3.91 (6H, s); 3.80 (3H, s); 3.70 (3H, s).13C NMR: 172.5, 168.2, 145.1,
143.0, 132.6, 127.4, 119.4, 118.2, 117.9, 110.8, 104.2 88.2, 56.8, 56.2, 53.6, 52.5
APCI-MS m/z 431.1 0.1 [M+H]+.
the wastes do not contain metals. The bioactivity profiles of the
products described in this Letter are currently under evaluation
in our laboratory.
Acknowledgements
We warmly thank University of Milan-Bicocca FAR 2010 for the
financial support and our students Giovanni Di Gennaro, Andrea
Bosisio and Lorenzo Beretta.
References and notes
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Tolppa, E.L.; Zoia, L. Biomimetics Learning from Nature. InTech, March 2010.
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11. Syrjänen, K.; Brunow, G. J. Chem. Soc., Perkin Trans. 1 1998, 3425–3429.
12. Arrieta-Baez, D.; Stark, R. E. Phytochemistry 2006, 67, 743–753.
13. Daquino, C.; Rescifina, A.; Spatafora, C.; Tringali, C. Eur. J. Org. Chem. 2009,
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1994, 1163–1165.
15. Ahmed, R.; Lehrer, M.; Stevenson, R. Tetrahedron Lett. 1973, 10, 747–750.
16. Bruschi, M.; Orlandi, M.; Rindone, B.; Rummakko, P.; Zoia, L. J. Phys. Org. Chem.
2006, 19, 592–596.
Compound
11:
Methyl(E-3-[2-(4-hydroxy-3,5-dimethoxy-phenyl-3-
methoxycarbonyl-2,3-dihydro-1-4-benzodioxan-7-yl]propen-2-enoate.
Amorphous red powder. UV kmax (MeOH) nm: 298, 239. 1H NMR (CDCl3, dH):
7.65 (1H, d, J = 15.11 Hz); 7.20 (1H, d, J = 8.3 Hz); 7.10 (1H, d, J = 1.8 Hz); 7.05
(1H, dd, J = 1.8 Hz, J = 8.3 Hz); 6.60 (2H, s); 6.32 (1H, d, J = 15.11 Hz); 5.63 (1H,
s); 5.18 (1H, d, J = 2.30 Hz); 4.86 (1H, d, J = 2.30 Hz); 3.94 (6H, s); 3.82 (3H, s);
3.68 (3H, s). 13C NMR: 172.3, 167.9, 146.0, 143.8, 132.9, 128.4, 127.6, 117.4,
115.8, 104.1, 74.1, 62.6, 56.7, 53.5, 52.3. APCI-MS m/z 431.1 0.1 [M+H]+.
21. Lemiere, G.; Gao, M.; De Groot, A.; Dommisse, R.; Lepoivre, J.; Pieters, L.; Buss,
V. J. Chem. Soc., Perkin Trans. 1 1995, 1775–1779.
22. Zoia, L.; Bruschi, M.; Orlandi, M.; Tolppa, E. L.; Rindone, B. Molecules 2008, 13,
129–148.
23. The HRP catalyzed oxidative cross-coupling reaction of ferulic acid amide (4)
and sinapic acid amide (5) having R-methyl benzyl amine as chiral auxiliary
was carried out with the same method described for the cross-coupling
reactions of p-hydroxycinnamic acid methyl esters. The preparation of
substrates 4 and 5 was achieved as follow: to a solution of sinapic acid (3,
4.46 mmol) or ferulic acid (2, 4.46 mmol) in anhydrous THF (40 mL), TEA
(0.62 mL, 5.1 mmol), DCC (1 g, 4.84 mmol) and (R)-methyl benzyl amine
(4.46 mmol) were added. The mixture was stirred at reflux for 4 h. The extent
of the reaction was monitored by TLC (hexane/ethyl acetate 1:1). Some drops
of acetic acid were added to remove the excess of DCC. After filtration the
solvent was evaporated under reduced pressure and the residue diluted in
ethyl acetate (100 mL). The resulting solution was washed with a pH 4 solution
of aqueous HCl (60 mL), with a 10% aqueous NaHCO3 solution (60 mL), with
saturated brine (60 mL) and finally dried over Na2SO4. The solvent was
evaporated under reduced pressure, and the residue was purified by silica gel
flash chromatography, (eluent ethyl acetate and petroleum ether 7:3). The
yield in 5 and 6 ranged from 30% to 35%.
17. Wallis, A. F. Tetrahedron Lett. 1969, 5287–5288.
18. Wallis, A. F. Aust. J. Chem. 1973, 26, 1571–1576.
19. The extracted crude reaction mixtures were previously analyzed by HPLC-
APCI-MS in order to have a wide indication of all the products present. The
instrument was settled on the positive ionization mode with a flow rate of
2.5 mL minꢀ1 of molecular nitrogen as the carrier gas. The APCI ion source
temperature was fixed at 250 °C and the detector voltage set to +1.5 kV. The
mass acquisition range was comprised within 100 and 600 amu with
100 amu sꢀ1 scan speed. Chromatographic separation was achieved by using
m (SUPELCO, Bellefonte, USA) column at
a
24. Bolzacchini, E.; Brunow, G.; Meinardi, S.; Orlandi, M.; Rindone, B.; Rummakko,
P. Tetrahedron Lett. 1998, 39, 3291–3294.
25. The fraction containing 17 collected by flash column chromatography (Merck
silica gel 60, 0.040–0.063 mm, 230–400 mesh ASTM) was successively
an Ascentis C18 15 cm ꢁ 4.6 mm ꢁ 5
l
25 °C and gradient elution with solvent A (water) and solvent B (methanol)
using the following elution profile: 0–10 min linear gradient from 90% A: 10% B
to 65% A: 45% B: linear gradient from 10 to 20 min to 30% A: 70% B and
continuing isocratic at 40% A: 70% B for eight additional minutes. Flow rate:
analyzed by RP-HPLC-DAD using a Gemini 5u C18 15 cm ꢁ 3.0 mm ꢁ 5
lm
(PHENOMENEX, USA) column at 25 °C and gradient elution with solvent A
(water) and solvent B (methanol) using the following elution profile: 0–6 min
isocratic B = 25%, from 6–20 min linear gradient from 25% to 70% of B and
0.6 mL minꢀ1. Injection volume: 60
lL.
20. Substrates (1, 2, and 3) were prepared by simple Fischer esterification reactions
of the substituted para-hydroxycinnamic acids, using methanol as the solvent
and sulphuric acid as the catalyst. Cross-coupling reactions were performed by
continuing isocratic 70%
B
for eight additional minutes. Flow rate:
L. The diasteroisomeric excess (%) was
0.8 mL minꢀ1. Injection volume: 40
l
preparing
a
solution with equimolar amounts of two substituted para-
concentration of 1.0 mmol in
evaluated on the basis of the ratio of the integral of the two peaks detected at
298 nm in the diode array extracted chromatogram. The value of
[diasteroisomer1 + diasteroisomer2] is the yield of 17 reported in Table 3
(27%), the ratio of the two peak integral was 2.2.
hydroxycinnamic acid methyl esters at
a
dioxane (14 mL) and 0.02 M phosphate/citric acid buffer pH 3.5 (4.0 mL).
This solution was added of a 0.86 M aqueous hydrogen peroxide solution
(0.60 mL, 0.5 mmol) and aqueous HRP (0.93 mL, 837 U) at 0 °C in small
portions over 15 min. The mixture was then stirred at 0 °C for 30 min and then
allowed to reach room temperature. The extents of the enzymatic reactions
were determined through the decrease in TLC analysis for both the substrates.
After 4 h a saturated aqueous NaCl solution (20 mL) was added. The dioxane
was then evaporated under reduced pressure and the resulting solution was
Compound 17 1H NMR (CDCl3, dH): 7.64 (1H, d, 15.07); 7.34–7.11 (10H
aromatic) 7.03 (1H, s); 6.98 (1H, s); 6.63 (2H, s); 6.58 (1H, d, J = 15.09 Hz); 6.16
(1H, d, J = 7.07 Hz); 5.61 (1H, s,); 5.53–5.39 (2H, m), 5.20 (broad), 4.44 (broad),
4.32 (1H, t, J = 7.10); 3.92 (6H, s); 3.88 (3H, s) 1.42–1.48 (6H,m). APCI-MS m/z
623.3 0.1 [M+H]+.