J. Cai et al. / European Journal of Medicinal Chemistry 55 (2012) 409e419
417
5.1.9. 2-(2-(2-(2-(4-isobutylphenyl)propanoyloxy)ethoxy)ethoxy)
1H NMR (300 MHz, CDCl3)
d: 2.46 (s, 6H, OCOCH3), 3.88 (s, 2H,
ethyl 4,5-diacetoxy-9,10-dioxo-9,10-dihydroanthracene-2-
carboxylate (6c)
OCOCH2), 4.52e4.55 (m, 2H, CH2CH2), 4.61e4.64 (m, 2H, CH2CH2),
6.48 (d, 1H, J ¼ 8.4, AreH), 6.86e6.91 (m, 3H, AreH), 7.22e7.25 (m,
3H, AreH), 7.44 (dd, 1H, J1 ¼ 1.2 Hz, J2 ¼ 8.0 Hz, AreH), 7.80 (t, 1H,
J ¼ 7.9, AreH), 7.98 (s, 1H, AreH), 8.24 (dd, 1H, J1 ¼ 1.2 Hz,
Preparation of 6c is followed the procedure for 6a described
above. Yield: 80%. Mp: 46e49 ꢀC. 1H NMR (300 MHz, CDCl3)
d: 0.88
(d, 6H, J ¼ 6.6, CH(CH3)2), 1.48 (d, 3H, J ¼ 7.2, CHCH3), 1.78e1.85 (m,
1H, CH(CH3)2), 2.43 (d, 2H, J ¼ 7.2, CH2CH(CH3)2), 2.45 (s,
6H,OCOCH3), 3.57e4.54 (m, 13H, CH2CH2 and CHCH3), 7.07 (d, 2H,
J ¼ 8.1, AreH), 7.20 (d, 2H, J ¼ 8.1, AreH), 7.43 (dd, 1H, J1 ¼ 1.2 Hz,
J2 ¼ 8.0 Hz, AreH), 7.79 (t,1H, J ¼ 7.9, AreH), 8.04 (s,1H, AreH), 8.25
(dd, 1H, J1 ¼ 1.2 Hz, J2 ¼ 7.8 Hz, AreH), 8.83 (s, 1H, AreH); 13C NMR
J2 ¼ 7.9 Hz, AreH), 8.78 (s, 1H, AreH); 13C NMR (75 MHz, CDCl3)
d:
20.7, 20.8, 36.9, 62.2, 63.8, 115.9, 120.6, 123.0, 124.8, 125.0, 125.3,
125.7, 127.7, 128.2, 129.0, 130.0, 130.5, 130.6, 130.8, 134.0, 134.5,
134.7,135.5,136.9,142.7,149.5,149.7,163.4,168.8,169.0,171.4,180.1,
180.5; IR (cmꢁ1): 3444, 3080, 2933, 2360, 1772, 1729, 1675, 1594,
1506,1456, 1371,1332,1280,1256,1097,1021, 921, 881, 770, 747; MS
(ESI) m/z: 690.3 [M þ H]þ, 728.3 [M þ K]þ; Anal. Calcd for
C35H25Cl2NO10: C, 60.88; H, 3.65; N, 2.03. Found: C, 60.76; H, 3.78;
N, 2.12%.
(75 MHz, CDCl3) d: 18.5, 20.9, 21.0, 22.3, 30.1, 45.0, 63.8, 65.1, 68.9,
69.2, 70.6, 70.7, 76.7, 77.0, 77.3, 125.6, 125.7, 126.4, 127.2, 128.4,
129.3, 130.5, 130.8, 134.4, 134.7, 135.0, 135.8, 137.7, 140.5, 150.2,
150.3, 164.0, 169.1, 169.3, 174.7, 180.5, 181.2; IR (cmꢁ1): 3469, 3415,
3136, 3014, 2959, 2874, 1772, 1727, 1670, 1605, 1452, 1395, 1325,
1270, 1194, 1098, 1023, 928, 885, 872, 797, 779, 737, 684, 624, 584,
544; MS (ESI) m/z: 711.2 [M þ Na]þ; Anal. Calcd for C38H40O12: C,
66.27; H, 5.85. Found: C, 66.39; H, 5.52%.
5.1.13. 2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-
3-yl)acetoxy)ethyl 4,5-diacetoxy-9,10-dioxo-9,10-
dihydroanthracene-2-carboxylate (6g)
Preparation of 6g is followed the procedure for 6a described
above. Yield: 79%. Mp: 108e110 ꢀC. 1H NMR (300 MHz, CDCl3)
d:
5.1.10. 2-(2-acetoxybenzoyloxy)ethyl 4,5-diacetoxy-9,10-dioxo-
9,10-dihydroanthracene-2-carboxylate (6d)
2.37 (s, 3H, CH3), 2.46 (s, 6H, OCOCH3), 3.70 (s, 2H, CH2), 3.74 (s, 3H,
OCH3), 6.49 (s, 1H, AreH), 6.65e6.71 (m, 2H, AreH), 7.43e7.53 (m,
3H, AreH), 7.79e7.83 (m, 3H, AreH), 7.91 (s,1H, AreH), 8.19 (dd,1H,
J1 ¼1.1 Hz, J2 ¼ 7.9 Hz, AreH), 8.65 (s, 1H, AreH); 13C NMR (75 MHz,
Preparation of 6d is followed the procedure for 6a described
above. Yield: 87%. Mp: 198e200 ꢀC. 1H NMR (300 MHz, CDCl3)
d:
2.33 (s, 3H, OCOCH3), 2.45 (s, 6H, OCOCH3), 4.63e4.66
(m, 2H, eCH2), 4.69e4.72 (m, 2H, eCH2), 7.12 (d, 1H, J ¼ 0.9,
AreH), 7.33 (m, 1H, AreH), 7.44 (dd, 1H, J1 ¼ 1.3 Hz, J2 ¼ 8.0 Hz,
AreH), 7.61 (m, 1H, AreH), 7.80 (t, 1H, J ¼ 7.9, AreH), 8.04e8.05 (m,
2H, AreH), 8.25 (dd, 1H, J1 ¼ 1.3 Hz, J2 ¼ 7.8 Hz, AreH), 8.84 (s, 1H,
CDCl3) d: 21.0, 21.1, 30.3, 55.6, 62.2, 63.6, 97.5, 101.2, 111.6, 112.1,
114.9, 125.7, 126.2, 128.4, 129.1, 130.4, 130.5, 130.6, 130.7, 131.2,
133.9, 134.4, 134.6, 135.0, 135.1, 136.1, 139.2, 150.1, 150.2, 156.0,
163.6, 168.2, 169.1, 169.3, 170.6, 180.4, 181.0; IR (cmꢁ1): 3442, 3081,
2934, 2359, 1775, 1733, 1679, 1594, 1476, 1456, 1368, 1326, 1257,
1195, 1166, 1094, 1022, 926, 746, 670; MS (ESI) m/z: 752.14
[M þ H]þ; Anal. Calcd for C40H30ClNO12: C, 63.88; H, 4.02; N, 1.86.
Found: C, 63.67; H, 3.95; N, 1.75%.
AreH); 13C NMR (75 MHz, CDCl3)
d: 20.9, 21.0, 62.5, 63.7, 122.6,
123.9, 125.6, 126.1, 126.4, 130.5, 130.8, 131.9, 134.2, 134.3, 134.7,
135.0, 135.3, 150.2, 150.3, 150.9, 163.8, 164.0, 169.1, 169.2, 169.5,
181.0; IR (cmꢁ1): 3462,1779,1733,1717, 1674,1451, 1373,1260, 1193,
1095, 1023, 920, 745, 701; MS (ESI) m/z: 592.3 [M þ NH4]þ, 597.3
[M þ Na]þ, 613.2 [M þ K]þ; Anal. Calcd for C30H22O12: C, 62.72; H,
3.86. Found: C, 62.55; H, 3.73%.
5.1.14. 2-(2-(4-isobutylphenyl)propanoyloxy)ethyl 4,5-dihydroxy-
9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (7a)
Compound 6a (0.55 g, 0.92 mmol) and triethylamine (3 mL,
21.35 mmol) were added to acetone (30 mL) and water (2 mL). The
solution was heated to 50 ꢀC for 6 h, the solvent was removed
under reduced pressure and the residue was poured into water,
the pH adjusted to 6 with 10% HCl. The water layer was extracted
by dichloromethane and the organic layer was separated, washed
with brine, dried over Na2SO4, and concentrated under reduced
pressure to give a crude product, which was purified by chroma-
tography (AcOEt/pet ¼ 1:3) on silica gel to afford 7a as an orange-
yellow solid (0.36 g, 76%). Mp: 85e87 ꢀC. 1H NMR (300 MHz,
5.1.11. 2-(2-(6-methoxynaphthalen-2-yl)propanoyloxy)ethyl 4,5-
diacetoxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (6e)
Preparation of 6e is followed the procedure for 6a described
above. Yield: 81%. Mp: 134e137 ꢀC. 1H NMR (300 MHz, CDCl3)
d:
1.56 (d, 3H, J ¼ 7.1, CHCH3), 2.46 (s, 6H, OCOCH3), 3.70 (s, 3H,
OCH3), 3.86e3.88 (m, 1H, CHCH3), 4.41e4.57 (m, 4H, CH2CH2),
6.84e6.86 (m, 2H, AreH), 7.46e7.55 (m, 5H, AreH), 7.73e7.80 (m,
2H, AreH), 8.22 (d, 1H, J ¼ 1.2, AreH), 8.42 (s, 1H, AreH); 13C
NMR (75 MHz, CDCl3)
d
: 18.0, 21.0, 21.1, 45.3, 55.1, 61.7, 63.4,
CDCl3)
d
: 0.83 (d, 6H, J ¼ 6.6, CH(CH3)2), 1.51 (d, 3H, J ¼ 7.2,
100.7, 105.5, 118.8, 125.6, 125.8, 125.9, 126.1, 127.1, 128.9, 129.2,
130.3, 130.4, 133.5, 134.3, 134.4, 134.8, 134.9, 135.2, 150.0, 150.2,
157.4, 163.5, 169.1, 169.3, 174.4; IR (cmꢁ1): 3445, 3087, 2939,
2360, 2343, 1772, 1728, 1678, 1457, 1373, 1333, 1276, 1207, 1096,
1028, 921, 863, 809, 743, 693; MS (ESI) m/z: 647.2 [M þ Na]þ;
Anal. Calcd for C35H28O11: C, 67.30; H, 4.52. Found: C, 67.65; H,
4.78%.
CHCH3), 1.72e1.81 (m, 1H, CH(CH3)2), 2.36 (d, 2H,
J
¼
7.1,
CH2CH(CH3)2), 3.71e3.78 (m, 1H, CHCH3), 4.42e4.56 (m, 4H,
CH2CH2), 7.03 (d, 2H, J ¼ 8.1, AreH), 7.19 (d, 2H, J ¼ 8.1, AreH), 7.34
(dd, 1H, J1 ¼ 1.2 Hz, J2 ¼ 8.4 Hz, AreH), 7.73e7.76 (m, 1H, AreH),
7.86 (s, 1H, AreH), 7.89 (dd, 1H, J1 ¼ 1.2 Hz, J2 ¼ 7.5 Hz, AreH),
8.37 (s, 1H, AreH), 11.96 (s, 1H, OH), 12.02 (s, 1H, OH); 13C NMR
(75 MHz, CDCl3) d: 18.3, 22.3, 30.1, 45.0, 62.0, 63.6, 115.8, 118.3,
120.3, 120.4, 124.9, 125.4, 127.1, 129.3, 133.5, 133.9, 137.3, 137.5,
137.8, 140.5, 162.4, 164.0, 174.4, 180.7, 192.8; IR (cmꢁ1): 3447, 2953,
2931, 2360, 1735, 1672, 1625, 1507, 8451, 1411, 1375, 1269, 1238,
1200, 1158, 1088, 1034, 994, 903, 872, 842, 745, 597; MS (ESI) m/z:
517.2 [M þ H]þ, 539.1 [M þ Na]þ; Anal. Calcd for C30H28O8: C,
69.76; H, 5.46. Found: C, 69.98; H, 5.22%.
5.1.12. 2-(2-(2-(2,6-dichlorophenylamino)phenyl)acetoxy)ethyl
4,5-diacetoxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate
(6f)
Diclofenac (4.3 g, 14.52 mmol), 5a (2.0 g, 4.85 mmol), DCC (3.0 g,
14.54 mmol) and DMAP were added into anhydrous dichloro-
methane (150 mL). After stirring for 1.5 h at room temperature,
water (20 mL) was added to stop the reaction. The precipitate was
filtered, the filtrate was washed with brine, dried over Na2SO4, and
concentrated under reduced pressure to give a crude product,
which was purified by chromatography (AcOEt/pet ¼ 1:2) on silica
gel to afford 6f as a pallid yellow solid (4.6 g, 46%). Mp: 149e151 ꢀC.
5.1.15. 2-(2-(2-(4-isobutylphenyl)propanoyloxy)ethoxy)ethyl 4,5-
dihydroxy-9,10-dioxo-9,10-dihydroanthracene-2-carboxylate (7b)
Preparation of 7b is followed the procedure for 7a described
above. Yield: 67%. Mp: 89e91 ꢀC. 1H NMR (300 MHz, CDCl3)
d
: 0.87
(d, 6H, J ¼ 6.7, CH(CH3)2), 1.48 (d, 3H, J ¼ 7.1, CHCH3), 1.82 (m, 1H,