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102.9, 105.6, 113.2, 116.5, 116.7, 123.9, 133.5, 133.7, 133.8, 151.2, 159.5, 160.9,
161.4, 162.5. MS m/z (%): 312 (M+, 59), 137 (100), 97 (36), 83 (37), 71 (51), 59
(79). Anal. Calcd for C18H16O5: C, 69.22; H, 5.16. Found: C, 69.24; H, 5.19.
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28. General procedure for the preparation of 3-phenyliodonium coumarinates I and II:
iodobenzene diacetate (10 mmol) was suspended in a solution of Na2CO3
(10 mmol) in water (100 mL) and was stirred for 30 min at room temperature.
To this solution was added a mixture of the corresponding 4-hydroxycoumarin
(10 mmol) and Na2CO3 (10 mmol) in water (100 mL). After the mixture was
stirred at room temperature for 14 h, the precipitate was collected by filtration,
washed with water (5 ꢀ 20 mL) and dried under vacuum. The resulting white
solid was used without further purification.
31. General procedure for the preparation of 4-benzyloxycoumarins 9–10: to a
solution of appropriate 4-hydroxycoumarin (1.5 mmol) in EtOH (15 mL), K2CO3
(4.5 mmol) and benzyl chloride (4.5 mmol) were added. The reaction was
stirred at reflux for 6 h under nitrogen atmosphere. After the solution was
cooled, K2CO3 was filtered off and the solution was evaporated to dryness. The
oil residue was treated with ether obtaining a precipitate that was filtered. It
was purified by FC (hexane/ethyl acetate, 7:3) or by crystallization to give the
desired compounds.
4-Benzyloxy-6-methylcoumarin (10). It was obtained with yield 45%. Mp:
220–223 °C. 1H NMR (CDCl3) d (ppm): 2.40 (s, 3H, CH3), 3.45–3.74 (s, 1H, H3),
4.25–4.70 (m, 2H, CH2), 6.79–7.03 (m, 2H, H7, H8), 7.04–7.33 (m, 4H, H20, H30,
H40, H50), 7.39–7.74 (m, 2H, H5, H60). 13C NMR (CDCl3) d (ppm): 21.9, 69.0, 87.5,
116.9, 117.5, 127.0, 127.1, 127.2, 127.6, 128.8, 128.9, 132.1, 135.4, 136.3, 149.8,
162.4, 169.9. MS m/z (%): 266 (M+, 100), 135 (57), 134 (65), 91 (52), 77 (27).
Anal. Calcd for C17H14O3: C, 76.68; H, 5.30. Found: C, 76.66; H, 5.28.
32. Ganguly, N. C.; Sukai, A. K.; Dutta, S.; De, P. J. Indian Chem. Soc. 2001, 78, 380.
33. General procedure for the preparation of 4-benzyloxy-3-phenylcoumarins 11–12:
to a solution of appropriate 4-hydroxycoumarin (0.7 mmol) in acetone (16 mL),
K2CO3 (1.4 mmol) and benzyl bromide (1.4 mmol) were added. The reaction
was stirred at reflux for 12 h under nitrogen atmosphere. After the solution
was cooled, K2CO3 was filtered off and the solution was evaporated to dryness.
The residue was treated with ether and the precipitate was filtered. It was
purified by FC (dichloromethane/petroleum ether, 9.5:0.5) or by crystallization
to give the desired compounds.
4-(Benzyloxy)-3-phenylcoumarin (11). It was obtained with yield 46%. Mp:
204–206 °C. 1H NMR (CDCl3) d (ppm): 4.65 (s, 2H, CH2), 7.11–7.18 (m, 2H, H20,
H60), 7.34–7.24 (m, 5H, H40, H6, H300, H400, H500), 7.37 (d, 1H, H8, J = 8.3), 7.45–
7.41 (m, 1H, H200), 7.48 (t, 2H, H30, H50, J = 7.4), 7.55 (d, 2H, H600, H7, J = 7.0),
7.84 (d, 1H, H5, J = 8.0). 13C NMR (CDCl3) d (ppm): 69.0, 100.3, 115.9, 117.6,
123.4, 125.3, 127.1, 127.3, 127.6, 127.8, 128.0, 128.4, 128.5, 128.6, 128.7, 128.8,
128.9, 132.6, 136.3, 152.4, 161.8, 166.9. MS m/z (%): 328 (M+, 100), 238 (45),
208 (44), 152 (32), 92 (65), 91 (61). Anal. Calcd for C22H16O3: C, 80.47; H, 4.91.
Found: C, 80.48; H, 4.89.
4-Benzyloxy-6-methyl-3-phenylcoumarin (12). It was obtained with yield 50%.
Mp: 173–175 °C. 1H NMR (CDCl3) d (ppm): 2.40 (s, 3H, CH3), 4.64 (s, 2H, CH2),
7.13–7.16 (m, 2H, H7, H20), 7.26 (s, 3H, H40, H60, H8), 7.34–7.30 (m, 3H, H300,
H400, H500), 7.47 (t, 2H, H30, H50, J = 7.5), 7.53 (m, 2H, H200, H600), 7.57 (s, 1H, H5).
13C NMR (CDCl3) d (ppm): 21.9, 69.1, 100.3, 116.8, 117.5, 127.0, 127.1, 127.2,
127.6, 127.8, 128.4, 128.6, 128.7, 128.8, 128.8, 128.9, 132.1, 132.6, 135.4, 136.3,
149.8, 161.7, 166.9. MS m/z (%): 342 (M+, 73), 208 (24), 92 (30), 91 (100). Anal.
Calcd for C23H18O3: C, 80.68; H, 5.30. Found: C, 80.66; H, 5.28.
34. The HL60 and the MCF-7 cells line were purchased from the American Type
Culture Collection. HL60 cells were grown in Iscove’s modified Dulbecco’s
medium with 2 mM
L-glutamine supplemented with 20% fetal bovine serum,
1
lg/ml amphotericin B, 100 units/ml penicillin, and 100 lg/ml streptomycin
(all from Life Technologies Invitrogen, Basel, Switzerland). MCF-7 cells were
cultured in RPMI 1640 medium containing penicillin (100 U/ml), streptomycin
(100 lg/ml), amphotericin B (1 lg/ml), 2 mM L-glutamine and 10% fetal bovine
serum (all from Life Technologies Invitrogen, Basel, Switzerland). All cells were
grown in a humidified incubator at 37 °C and 5% CO2. Cells were seeded into
96-well plates at a density of 2 ꢀ 106 per well and incubated at 37 °C with 5%
CO2. After 24 h incubation to allow cell attachment, cells were treated for 72 h
29. General procedure for the preparation of 3-aryl-4-hydroxycoumarins 3–8:
a
degassed solution of appropriated phenyl boronic acid (1.21 mmol) and P(t-
But)3 (0.109 mmol) in DME and H2O (4:1, 12.5 mL) was added to a mixture of
iodonium ylide (0.55 mmol), LiOH/H2O (1.65 mmol) and Pd(OAc)2
(0.027 mmol) under argon at room temperature. After being stirred at the
same temperature for 24–48 h. The resulting mixture was purified by FC
(hexane/ethyl acetate, 7:3) to give the desired compound.
with the acetylenic compounds in the range 0.1–100 lM. For the HL-60 cells it
is not necessary to wait the time of incubation to allow cell attachment
because the cells are in suspension. At the end of the exposure time, WST-1
was added at 1/10 of the total volume and after 60 min of incubation at 37 °C,
the absorbance was measured at 450 nm with a microplate reader (Wallac;
Perkin Elmer,Wellesley, MA, USA).
4-Hydroxy-3-(20,40-dimethoxyphenyl)-6-methylcoumarin (8). It was obtained
with yield 57%. Mp: 274–277 °C. 1H NMR (DMSO-d6) d (ppm): 2.30–2.44 (s, 3H,
CH3), 3.63–3.75 (s, 3H, OCH3), 3.75–3.86 (s, 3H, OCH3), 6.49–6.68 (m, 2H, H30,
H50), 7.02–7.13 (m, 1H, H60), 7.21–7.32 (m, 1H, H8), 7.37–7.51 (m, 1H, H7),
7.66–7.76 (s, 1H, H5). 13C NMR (DMSO-d6) d (ppm): 21.1, 55.9, 56.1, 99.2,
35. Chicca, A.; Pellati, F.; Adinolfi, B.; Matthias, A.; Massarelli, I.; Benvenuti, S.;
Martinotti, E.; Bianucci, A. M.; Bone, K.; Lehmann, R.; Nieri, P. Br. J. Pharmacol.
2008, 153, 879.