L. Xia et al. / European Journal of Medicinal Chemistry 86 (2014) 605e612
609
Table 2
The in vitro DPPH radical scavenging activities of compounds (7aek).
Compound
Concentration (
1.0
m
g/mL)a
IC50 (m
g/mL)a
25
50
100
7a
7b
7c
7d
7e
7f
7g
7h
7i
21.57 0.16
35.32 0.45
26.94 0.19
25.05 0.39
e
45.02 0.69
70.23 0.56
61.15 0.69
76.02 0.16
37.26 0.97
26.94 0.64
30.56 0.28
28.31 0.46
27.68 0.61
26.67 0.26
25.05 0.16
40.77 0.46
81.36 0.26
89.74 0.46
81.90 0.55
85.83 0.49
75.47 0.86
41.47 0.13
30.77 0.31
27.40 0.15
26.94 0.29
30.63 0.84
26.03 0.16
65.62 0.49
88.94 0.88
91.03 0.43
90.94 0.63
88.98 0.24
80.26 0.64
63.68 0.99
36.06 0.54
28.94 0.64
33.36 0.96
59.89 0.14
28.63 0.32
76.47 0.62
25.11 0.26
3.33 0.16
6.30 0.32
5.01 0.21
31.47 0.45
62.51 0.55
>100
>100
>100
77.62 0.22
>100
34.67 0.69
e
10.22 0.19
5.23 0.26
8.94 0.29
16.73 0.19
5.10 0.24
e
7j
7k
BHT
a
Values represent mean SE of three different reactions.
was washed with water then brine, and dried over Na2SO4. Evap-
oration the solvent yielded 4 (14.4 g, 90%), which was pure enough
for use in subsequent experiments without further purification. The
spectral data of 4 were in accord with literature values [53,59,60].
Compound 4 can also be prepared by the photoacylation of 1,4-
naphthoquinone with acetaldehyde followed by Ag2O mediated
oxidation, as previously described [53].
J ¼ 8.1 Hz, 1H), 7.61 (dd, J ¼ 8.1, 7.2 Hz, 1H), 7.47 (dd, J ¼ 8.1, 7.2 Hz,
1H), 5.82 (d, J ¼ 6.6 Hz, 1H), 3.76e3.71 (m, 1H), 3.68e3.61 (m, 1H),
3.41e3.35 (m, 2H), 2.59 (s, 3H), 1.92e1.81 (m, 1H), 0.90 (t, J ¼ 6.9 Hz,
6H); 13C NMR (75 MHz, CDCl3)
d 203.55, 158.86, 145.67, 129.93,
125.77, 125.22, 124.98, 124.92, 121.19, 113.49, 111.28, 105.57, 75.40,
41.22, 30.70, 28.44, 19.35, 19.25; IR (neat): 3064, 2958, 1713, 1631,
1452, 1391, 1282, 1110, 1025, 941, 887, 766 cmꢀ1; HRMS (EIþ): m/z:
calcd for C18H20O4: 300.1362, found 300.1360.
4.1.5. General procedure for the preparation of 5-hydroxy-4-acetyl-
2,3-dihydronaphtho[1,2-b]furan derivatives 7aek
4.1.5.4. 1-(2-Butoxy-5-hydroxy-2,3-dihydronaphtho[1,2-b]furan-4-
To
a
solution of methyl 1,4-dihydroxynaphthalene-2-
yl)ethanone (7d). Yellow liquid; yield 234 mg, 78%; 1H NMR
carboxylate (9, 218 mg, 1.0 mmol) and the corresponding olefin
(2.0 mmol) in MeCN (5.0 mL) was added cerium (IV) ammonium
nitrate (CAN, 5.0 mol%) at room temperature. The reaction was
monitored by TLC. After all starting material had been consumed,
water (10 mL) was added and the solution was extracted with ethyl
acetate (10 mL ꢃ 3). Evaporation of the solvent and purification by
silica gel column chromatography using hexane-ethyl acetate
(10:1) as eluant gave the desired products [48].
(300 MHz, CDCl3)
d
14.20, (s, 1H), 8.39 (d, J ¼ 8.4 Hz, 1H), 7.87 (d,
J ¼ 8.1 Hz, 1H), 7.60 (dd, J ¼ 8.1, 7.2 Hz, 1H), 7.46 (dd, J ¼ 8.4, 7.2 Hz,
1H), 5.82 (d, J ¼ 6.6 Hz, 1H), 3.98e3.91 (m, 1H), 3.66e3.60 (m, 2H),
3.39e3.33 (m, 1H), 2.57 (s, 3H), 1.61e1.50 (m, 2H), 1.42e1.30 (m,
2H), 0.90 (t, J ¼ 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3)
d 203.52,
158.83, 145.60, 129.90, 125.74, 125.17, 124.94, 124.87, 121.14, 113.43,
111.19, 105.34, 68.37, 41.20, 31.61, 30.66, 19.17, 13.76; IR (neat): 2977,
2928, 1733, 1623, 1450, 1393, 1248, 1112, 1004, 887, 846, 766,
640 cmꢀ1; HRMS (EIþ): m/z: calcd for C18H20O4: 300.1362, found
300.1360.
4.1.5.1. 1-(2-Ethoxy-5-hydroxy-2,3-dihydronaphtho[1,2-b]furan-4-
yl)ethanone (7a). Yellow liquid; yield 220 mg, 81%; 1H NMR
(300 MHz, CDCl3)
d
14.24, (s, 1H), 8.41 (d, J ¼ 8.4 Hz, 1H), 7.89 (d,
J ¼ 8.1 Hz, 1H), 7.62 (dd, J ¼ 8.1, 7.2 Hz, 1H), 7.48 (dd, J ¼ 7.8, 7.5 Hz,
1H), 5.86 (d, J ¼ 5.7 Hz, 1H), 4.07e3.97 (m, 1H), 3.73e3.64 (m, 2H),
3.40 (d, J ¼ 16.5 Hz,1H), 2.60 (s, 3H),1.25 (t, J ¼ 7.2 Hz, 3H); 13C NMR
4.1.5.5. 1-(5-Hydroxy-2-methoxy-2-methyl-2,3-dihydronaphtho[1,2-
b]furan-4-yl)ethanone (7e). Yellow solid; yield 103 mg, 38%; mp
124e125 ꢁC; 1H NMR (300 MHz, CDCl3)
d 14.23, (s, 1H), 8.42 (d,
(75 MHz, CDCl3)
d 203.57, 158.96, 145.65, 129.98, 125.84, 125.25,
J ¼ 8.4 Hz, 1H), 7.91 (d, J ¼ 8.1 Hz, 1H), 7.62 (dd, J ¼ 7.8, 7.2 Hz, 1H),
7.49 (dd, J ¼ 7.8, 7.2 Hz, 1H), 3.60 (d, J ¼ 16.8 Hz, 1H), 3.50 (d,
J ¼ 17.1 Hz, 1H), 3.35 (s, 3H), 2.62 (s, 3H), 1.78 (s, 3H); 13C NMR
125.02, 124.94, 121.18, 113.41, 111.24, 105.17, 64.09, 41.32, 30.74,
15.17; IR (neat): 2971, 1710, 1665, 1597, 1445, 1347, 1228, 1161, 1150,
1027, 944, 876, 764 cmꢀ1; HRMS (EIþ): m/z: calcd for C16H16O4:
272.1049, found 272.1050.
(75 MHz, CDCl3)
d 203.53, 158.92, 145.90, 130.04, 125.93, 125.36,
125.05, 124.68, 121.25, 113.84, 111.15, 110.76, 49.74, 45.44, 30.74,
24.27; IR (KBr): 2962, 1713, 1623, 1451, 1387, 1312, 1233, 1056, 849,
768, 642 cmꢀ1; HRMS (EIþ): m/z: calcd for C16H16O4: 272.1049,
found 272.1046.
4.1.5.2. 1-(5-Hydroxy-2-propoxy-2,3-dihydronaphtho[1,2-b]furan-4-
yl)ethanone (7b). Yellow liquid; yield 226 mg, 79%; 1H NMR
(300 MHz, CDCl3)
d
14.22, (s, 1H), 8.39 (d, J ¼ 8.1 Hz, 1H), 7.88 (d,
J ¼ 8.1 Hz, 1H), 7.61 (t, J ¼ 7.5 Hz, 1H), 7.47 (dd, J ¼ 7.8, 7.5 Hz, 1H),
5.83 (d, J ¼ 5.7 Hz, 1H), 3.94e3.87 (m, 1H), 3.69e3.35 (m, 3H), 2.58
(s, 3H), 1.68e1.52 (m, 2H), 0.90 (t, J ¼ 6.9 Hz, 3H); 13C NMR (75 MHz,
4.1.5.6. 1-(cis-2-Ethoxy-5-hydroxy-3-methyl-2,3-dihydronaphtho
[1,2-b]furan-4-yl)ethanone (7f). Yellow liquid; yield 132 mg, 46%;
mp 166e167 ꢁC; 1H NMR (300 MHz, CDCl3)
d 14.15 (s, 1H), 8.40 (d,
CDCl3)
d 203.56, 158.95, 145.70, 129.97, 125.82, 125.28, 125.02,
124.97, 121.20, 113.45, 111.29, 105.40, 70.35, 41.30, 30.72, 22.89,
10.52; IR (neat): 2962, 2874,1722, 1623,1452,1392,1281, 1111,1004,
888, 765 cmꢀ1; HRMS (EIþ): m/z: calcd for C17H18O4: 286.1205,
found 286.1209.
J ¼ 8.4 Hz, 1H), 7.87 (d, J ¼ 8.1 Hz, 1H), 7.66e7.45 (m, 2H), 5.88 (d,
J ¼ 6.3 Hz, 1H), 4.17e4.09 (m, 1H), 3.86e3.69 (m, 2H), 2.68 (s, 3H),
1.36 (t, J ¼ 7.2 Hz, 3H), 1.23 (t, J ¼ 6.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3)
d 203.42, 158.77, 146.62, 129.92, 126.04, 125.41, 124.97,
124.91, 121.49, 119.90, 110.96, 108.76, 66.42, 42.81, 30.07, 15.23,
14.48; IR (neat): 1629, 1451, 1387, 1320, 1240, 1157, 1090, 980, 918,
871, 770 cmꢀ1; HRMS (EIþ): m/z: calcd for C17H18O4: 286.1205,
found 286.1209.
4.1.5.3. 1-(5-Hydroxy-2-isobutoxy-2,3-dihydronaphtho[1,2-b]furan-
4-yl)ethanone (7c). Yellow liquid; yield 210 mg, 70%; 1H NMR
(300 MHz, CDCl3)
d
14.22, (s, 1H), 8.40 (d, J ¼ 8.4 Hz, 1H), 7.88 (d,