Evaluation of fused oxepinocoumarins as radicals scavengers 807
1600 cm−1; 1H NMR (CDCl3, 300 MHz) δ 3.42 (d, J= 5.9 Hz,
2H), 4.61 (d, J= 4.9 Hz, 2H), 5.09 (d, J= 12.8 Hz, 1H), 5.10
(d, J= 11.8 Hz, 1H), 5.34 (d, J= 11.8 Hz, 1H), 5.46 (d, J=
18.7 Hz, 1H), 5.85–6.14 (m, 2H), 6.24 (d, J= 8.9 Hz, 1H),
6.77 (s, 1H), 7.22 (s, 1H), 7.64 (d, J= 8.9 Hz, 1H); 13C NMR
(CDCl3, 75 MHz) δ: 33.7, 69.1, 99.7, 112.0, 112.9, 116.3,
117.9, 126.3, 128.0, 132.1, 135.8, 143.4, 154.5, 159.3, 161.3;
MS (EI) 242 (M+·, 64%), 214 (8), 201 (61), 173 (39), 145
(30), 117 (44), 115 (100), 91 (49). Anal. Calcd for C15H14O3:
C, 74.36; H, 5.83. Found: C, 74.52; H, 5.59.
portions during 15 h), m.p. 126–128°C (DCM–hexane); IR
1
(KBr) 3079, 2939, 2843, 1732, 1593, 1568 cm−1; H NMR
(CDCl3, 300 MHz) δ 2.63 (s, 3H), 3.90 (d, J= 5.9 Hz, 2H),
4.64 (t, J= 2.0 Hz, 2H), 5.46 (dt, J1 = 10.8 Hz, J2 = 2.0 Hz,
1H), 5.88–5.98 (m, 1H), 6.26 (s, 1H), 7.19 (d, J= 8.9 Hz,
1H), 7.28 (d, J= 8.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
δ: 25.0, 26.1, 72.0, 116.4, 117.5, 120.8, 124.6, 124.9, 128.4,
136.2, 150.9, 152.7, 155.5, 159.1; MS (ESI) 229 [M+H]+,
251 [M+Na]+. Anal. Calcd for C14H12O3: C, 73.67; H, 5.30.
Found: C, 73.85; H, 5.51.
6,9-Dihydro-2H-oxepino[3,2-g]chromen-2-one (9)
(97% yield− 3.9 mol% of 6 was added in four portions
during 15 h), m.p. 118–120°C (DCM–hexane); IR (KBr)
3080, 2927, 1732, 1622, 1561 cm−1; 1H NMR (CDCl3,
300 MHz) δ 3.53 (d, J = 3.0, 2H), 4.67 (dd, J1 = 3.0, J2 = 2.0,
2H), 5.52 (dt, J1 = 11.8 Hz, J2 = 2.0 Hz,1H), 5.86–5.97 (m,
1H), 6.34 (d, J = 9.9 Hz, 1H), 7.04 (s, 1H), 7.21 (s, 1H),
7.43 (d, J = 9.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ:
31.1, 71.6, 110.2, 115.0, 115.1, 125.8, 127.2, 127.7, 132.9,
143.0, 155.0, 160.9, 161.8; MS (ESI) 215 [M+H]+, 237
[M+Na]+. Anal. Calcd for C13H10O3: C, 72.89; H, 4.71.
Found: C, 73.01; H, 4.97.
7-Allyl-8-hydroxy--2H-chromen-2-one (17) (89%
yield, after the reflux of compound 16 in ethyleneglycol
for 20 h), m.p. 151–153°C (DCM–hexane) (lit48. 154°C).
7-Allyl-8-(allyloxy)-2H-chromene-2-one (18) (82%
yield), m.p. 51–53°C (acetone); IR (Nujol) 3040, 1715,
1
1590 cm−1; H NMR (CDCl3, 300 MHz) δ 3.50 (d, J= 6.9
Hz, 2H), 4.70 (d, J= 5.9 Hz, 2H), 5.07 (d, J= 17.7 Hz, 1H),
5.09 (d, J= 8.9 Hz, 1H), 5.25 (d, J= 10.8 Hz, 1H), 5.40 (d,
J= 15.8 Hz, 1H), 5.88–6.0 (m, 1H), 6.05–6.18 (m, 1H),
6.36 (d, J= 9.8 Hz, 1H), 7.08 (d, J= 7.9 Hz, 1H), 7.15 (d,
J= 7.9 Hz, 1H), 7.67 (d, J= 9.8 Hz, 1H); 13C NMR (CDCl3,
75 MHz) δ: 34.3, 74.6, 115.6, 116.5, 118.2, 118.4, 122.3,
125.4, 128.4, 133.5, 135.9, 137.5, 143.7, 147.1, 160.1; MS
(ESI) 265 [M+Na]+. Anal. Calcd for C15H14O3: C, 74.36; H,
5.83. Found: C, 74.41; H, 5.96.
5-Allyl-6-hydroxy-4-methyl-2H-chromen-2-one
(12) (78% yield, after the reflux of compound 11 in
ethyleneglycol for 16 h), m.p. 176–178°C (EtOH) (lit47.
176–177°C).
7,10-Dihydro-2H-oxepino[3,2-h]chromen-2-one
(19) (83% yield− 6.9 mol% of 6 was added in three por-
tions over 12 h), m.p. 109–111°C (ethyl acetate); IR (Nujol)
5-Allyl-6-(allyloxy)-4-methyl-2H-chromene-2-one
(13) (83% yield, after 4 h of refluxing), m.p. 62–64°C (ace-
tone); IR (KBr) 3097, 2978, 2934, 1695, 1598, 1563 cm−1;
1H NMR (CDCl3, 300 MHz) δ 2.67 (s, 3H), 3.87 (m, 2H),
4.57 (dd, J1 = 4.9 Hz, J2 = 2.0 Hz, 2H), 4.75 (dq, J1 = 18.7 Hz,
J2 = 2.0 Hz, 1H), 5.08 (dq, J1 = 10.8 Hz, J2 = 2.0 Hz, 1H), 5.28
(dt, J1 = 11.8 Hz, J2 = 3.0 Hz, 1H), 5.41 (dt, J1 = 18.7 Hz, J2 = 2.0
Hz, 1H), 5.96–6.13 (m, 2H), 6.25 (s, 1H), 7.12 (d, J= 8.9 Hz,
1H), 7.23 (d, J= 8.9 Hz, 1H); 13C NMR (CDCl3, 75 MHz)
δ: 24.2, 30.6, 70.2, 115.5, 116.3, 116.4, 117.3, 117.7, 120.0,
126.1, 133.0, 136.8, 149.1, 153.4, 153.6, 160.3; MS (EI) 256
(M+·, 73%), 215 (27), 201 (21), 200 (42), 187 (16), 171 (18),
115 (48), 91 (40), 41 (100). Anal. Calcd for C16H16O3: C,
74.97; H, 6.30. Found: C, 75.12; H, 6.27.
1
3050, 1710, 1590 cm−1; H NMR (CDCl3, 300 MHz) δ 3.58
(d, J= 2.6, 2H), 4.71 (d, J= 2.6, 2H), 5.53 (dt, J1 = 12.0 Hz,
J2 = 2.6 Hz,1H), 5.80–5.91 (m, 1H), 6.39 (d, J= 9.5 Hz, 1H),
7.02 (d, J= 7.7 Hz, 1H), 7.15 (d, J= 7.7 Hz, 1H), 7.69 (d, J=
9.5 Hz, 1H); 13C NMR (CDCl3, 75 MHz) δ: 31.7, 70.8, 114.7,
117.0, 121.5, 123.7, 125.2, 126.6, 128.6, 142.5, 144.5, 155.3,
160.5; MS (ESI) 237 [M+Na]+. Anal. Calcd for C13H10O3: C,
72.89; H, 4.71. Found: C, 73.08; H, 4.60.
Biological assay
In vitro experiments
In the in vitro assays, each experiment was performed
at least in triplicate and the standard deviation of absor-
bance was <10% of the mean.
4-Methyl-8,11-dihydro-3H-oxepino[3,2-f]chromen-
3-one (14) (98% yield− 2.2 mol% of 6 was added in four
Table 1. Interaction % with DPPH at 0.1mM; competition % of compounds with DMSO for hydroxyl radical (HO %); inhibition of lipid
peroxidation at 0.1mM (LP %); in vitro inhibition of soybean LOX IC50 μM.
No.
7a
DPPH % (20/60min 0.1mM)
HO· % (0.1mM)
LP % at 0.1 mM
LOX inhibitor (IC50 μM)
Clog Pa
2.56
19/24
3/12
94
61
nd
nd
65
87
92
310
180
nd
7b
3.06
9
13/13
no
nd
nd
nd
2.56
14
nd
3.06
19
10/10
81/83
nd
2.56
NDGA
CA
600
Trolox
88
73
aBiobyte Corp., C-QSAR Database 201 West 4th Str., Suite 204, Claremont CA, California 91711, USA.
NDGA, nordihydroguaiaretic acid; CA, caffeic acid; nd, not detectable under the reported experimental conditions; each experiment was
performed at least in triplicate and the standard deviation of absorbance was <10% of the mean.
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