G.-L. Liu et al. / European Journal of Medicinal Chemistry 54 (2012) 582e590
589
(2H, d, -CH2-), 4.95e4.99 (2H, m, H-300), 5.28e5.45 (2H, m, H-30),
5.89e5.96 (1H, m, H-20), 6.03e6.11 (1H, m, H-200), 6.29e6.31 (1H, d,
H-3), 7.07e7.09 (1H, d, H-6), 7.58e7.60 (1H, d, H-5), 7.99e8.00 (1H,
CH3Oe), 6.220 (1H, s, H-3), 6.97e6.99 (1H, d, H-8), 6.98e6.99 (1H,
d, H-6), 7.69e7.70 (1H, d, H-5); 13CNMR (DMSO): 18.62 (CH3e),
56.38 (CH3Oe), 101.17 (C-8), 111.58 (C-3), 112.59 (C-6), 113.57
(C-10), 126.94 (C-5), 153.94 (C-9), 155.24 (C-4), 160.64 (C-7), 162.84
(C-2).
13
d, H-4); CNMR (DMSO): 26.93 (C-100), 69.31 (C-10), 109.60 (C-6),
112.89 (C-3), 113.71 (C-8), 115.00 (C-10), 115.88 (C-30), 117.74 (C-300),
127.97 (C-5), 133.66 (C-200), 135.53 (C-20), 145.15 (C-4), 152.86 (C-9),
159.16 (C-7), 160.71 (C-2); 13CNMR(DMSO) DEPT 90ꢀ: 109.60 (C-6),
112.89 (C-3), 127.97 (C-5), 133.66 (C-200), 135.53 (C-20), 145.15 (C-4);
13CNMR(DMSO) DEPT 135ꢀ: 26.93 (C-100), 69.31 (C-10), 115.88 (C-30),
117.74 (C-300), 109.60 (C-6), 112.89 (C-3), 127.97 (C-5), 133.66 (C-200),
135.53 (C-20), 145.15 (C-4).
5.2.3.12. 7-(2-Allyloxy-2-methyl)-4-Methyl coumarin (15). MS (m/z,
%): 231.07. (Mþ þ H, 100). 1HNMR (DMSO): 1.79 (3H, s, eCH3), 2.41
(3H, d, eCH3), 4.61 (1H, dd, eCH2e), 5.00e5.09 (2H, d, CH2]), 6.22
(1H, d, H-3), 6.99 (1H, d, H-8), 7.00e7.01 (1H, d, H-6), 7.68e7.70 (1H,
d, H-5); 13CNMR (DMSO): 18.60 (CH3e), 19.60 (eCH3), 71.84
(eCH2e), 102.00 (C-8), 111.67 (CH2]), 113.08 (C-3), 113.25 (C-6),
5.2.3.6. 8-Allyl-7-(2-methyl-allyloxy) coumarin (7). MS (m/z, %):
256.03. (Mþ, 100). 1HNMR(DMSO): 1.79 (2H, s, eCH3), 3.49e3.51
(2H, d, H-100), 4.61 (2H, s, H-10), 4.95e4.97 (2H, m, H-300),
4.97e5.09 (2H, m, H-30), 5.89e5.95 (1H, m, H-200), 6.28e6.29 (1H, d,
H-3), 7.05e7.07 (1H, d, H-6), 7.57e7.58 (1H, d, H-5), 7.97e7.99 (1H,
113.70 (C-10), 126.93 (C-5), 140.72 (
(C-4), 160.60 (C-7), 161.77 (C-2).
), 153.88 (C-9), 155.13
C
5.2.3.13. 7-(2-Allyloxy-1,1-dimethyl)-4-methyl coumarin (16). MS
(m/z, %): 244.93 (Mþ þ H, 100). 1HNMR (DMSO): 1.74 (3H, s, H-10),
1.76 (3H, s, H-10), 2.52 (3H, d, eCH3), 4. 63e4.65 (2H, d, CH2]),
5.44e5.47 (1H, m, eCH]), 6.20 (1H, d, H-3), 6.94e6.96 (1H, m, H-
8), 6.96e6.98 (1H, m, H-6), 7.66e7.67 (1H, d, H- 5); 13CNMR
13
d, H-4); CNMR(DMSO): 19.62 (eCH3), 26.94 (C-100), 71.96 (C-10),
109.43 (C-6), 112.80 (C-3), 112.85 (C-30), 113.12 (C-8), 114.87 (C-10),
115.84 (C-300), 127.94 (C-5), 135.55 (C-8), 140.91 (
), 145.13
C
(C-4), 152.85 (C-9), 159.17 (C-7), 160.70 (C-2); 13CNMR (DMSO)
DEPT 90ꢀ: 109.43 (C-6), 112.80 (C-3), 127.94 (C-5), 135.55 (C-8),
145.13 (C-4); 13CNMR(DMSO) DEPT 135ꢀ: 26.94 (C-100), 71.96 (C-10),
112.85 (C-30), 115.84 (C-300); 19.62 (CH3e), 109.43 (C-6), 112.80
(C-3), 127.94 (C-5), 135.55 (C-8), 145.13 (C-4).
(DMSO): 18.53 (C-10), 18.59 (C-10), 25.89 (eCH3), 65.56 (
C
),
101.78 (C-8), 111.50 (C-3), 113.04 (C-6), 113.45 (CH2]), 119.65 (C-
10), 126.83 (C-5), 138.50 (]CHe), 153.88 (C-9), 155.17 (C-4), 160.63
(C-7), 162.01 (C-2).
5.2.3.7. 8-Allyl-7-(2-allyloxy-1,1-dimethyl) coumarin (8). MS (m/z,
%): 270.86. (Mþ, 100). 1HNMR (DMSO): 1.73 (3H, s, eCH3), 1.76 (3H,
s, eCH3), 3.45e3.46 (2H, d,H-100), 4.66e4.68 (2H, m,H-300),
4.93e4.97 (2H, m, H-30), 5.44e5.46 (1H, m, H-10), 5.87e5.92 (1H, m,
H-200), 6.27e6.29 (1H, d, H-3), 7.08e7.09 (1H, d, H-6), 7.57e7.58 (1H,
d, H-5), 7.97e7.99 (1H, d, H-4); 13CNMR(DMSO): 18.59 (C-100), 25.90
O
5.2.3.14. 7-Allyloxy-4-methyl coumarin (17). MS (m/z, %): 217.03.
(Mþ þ H, 100). 1HNMR (DMSO): 2.40 (3H, s, eCH3), 4.9e4.70 (2H, d,
eCH2e), 5.29e5.32 (1H, dd, CH2]), 5.43e5.46 (1H, dd, CH2]),
6.03e6.11 (1H, m, ]CHe), 6.22 (1H, s, H-3), 6.98e6.99 (1H, d, H-8),
7.00 (1H, s, H-6), 7.68e7.69 (1H, d, H-5); 13CNMR (DMSO): 18.60
(CH3e), 69.26 (eCH2e), 101.94 (C-8), 111.67 (C-3), 113.01 (C-6),
113.68 (CH2]), 118.54 (C-10), 126.94 (C-5), 133.46 (]CHe), 153.87
(C-9), 155.15 (C-4), 160.06 (C-7), 161.67 (C-2).
(eCH3), 26.89 (eCH3), 65.92 (
), 109.65 (C-6), 112.70
C
(C-30), 112.99 (C-300), 114.99 (C-8), 115.79 (C-3), 119.89 (C-10), 127.91
(C-5), 135.58 (C-200), 138.26 (C-20), 145.16 (C-4), 152.85 (C-9), 159.56
(C-7), 160.74 (C-2).
5.2.4. The procedure for osthol
Osthol was synthesized according to Olefin metathesis
procedure using Compound 9 and 3-chloro-3-methyl-1-butylene
together with Grubbs 2nd catalyst in CH2Cl2. The Grubbs 2nd
catalyst (50 mg) was added in 2-methyl-2-butylene (15 mL) and
CH2Cl2 (15 mL). Then the mixture was refluxed under the
atmosphere of nitrogen at 45 ꢀC for 30 min. Compound 9
(350 mg) dissolved in dichloromethane (50 mL) was added in
the mixture by dropping funnel at 40 ꢀC, the flow rate was
controlled in 2.5 mL/min. The reaction mixture was further
5.2.3.8. 8-Allyl-7-methyloxy coumarin (9). MS (m/z, %): 216.08. (Mþ,
100). 1HNMR (CDCl3): 3.59e3.61 (2H, d, eCH2e), 3.93 (3H, s, CH3e),
4.97e5.08 (1H, m, ]CH2), 5.93e5.99 (1H, m, ]CHe), 6.24e6.26
(1H, d, H-3), 6.85e6.87 (1H, d, H-6), 7.27e7.35 (1H, m, H-5),
7.63e7.65 (1H, s, H-4); 13CNMR (CDCl3): 160.35 (C-2), 152.93
(C-9), 143.70 (C-4), 135.08 (]CHe), 126.65 (C-5), 116.15 (C-10),
115.33 (C-3), 113.04 (CH2]), 112.94 (C-8), 107.36 (C-6), 56.10
(CH3e), 26.75(eCH2e).
refluxed for 1.5
h with continuous stirring until complete
5.2.3.9. 7-Methyloxy coumarin (10). MS (m/z, %): 177.05. (Mþ þ H,
100).1HNMR (CDCl3): 3.82 (1H, s, eOCH3), 6.30 (1H, d, H-3), 7.70 (1H,
d, H-4), 7.43 (1H, d, H-5), 6.88 (1H, m, H-6), 6.84 (1H, d, H-8); 13CNMR
(CDCl3): 55.8 (eOCH3),100.6 (C-8),111.0 (C-5),112.5 (C-4a),113.4 (C-
3), 129.8 (C-5), 143.5 (C-4), 158.9 (C-8a), 160.2 (C-7), 160.8 (C-2).
consumption of the starting material checked by TLC. Then the
mixture was cooled to room temperature and concentrated
under reduced pressure (The reaction mixture was cooled and
the excess of solvent was removed under reduced pressure to
obtain a solid residue). The residue was purified by silica gel
column chromatography using petroleum ether-ethyl acetate as
eluent to produce a white needle shaped crystallite (307 mg).
Yield 77.65%.
5.2.3.10. 7-(2-Methyl-2- allyloxy) coumarin (11). MS (m/z, %):
217.08. (Mþ þ H, 100). 1HNMR (DMSO): 1.78 (3H, s, ]CH2e), 4.59
(2H, s, eCH2e), 4.99 (2H, d, H-6), 5.08 (1H, d, CH2]), 6.29e6.31
(1H, d, H-3), 6.96e6.9 (1H, d, H-8), 76.99e7.01 (1H, d, H-6),
7.62e7.65 (1H, d, H-5), 7.99e8.01 (1H, d, H-5); 13CNMR (DMSO):
18.63 (]CHe), 70.89 (CH3e), 100.98 (C-8), 111.94 (]CH2), 112.05
(C-6), 112.31 (C-3), 112.39 (C-10), 128.97 (C-5), 139.71 (C-4), 143.79
5.2.4.1. Osthol. MS (m/z, %): 245.06. (Mþ þ H, 100). 1HNMR
(DMSO): 1.62 (3H, s, eCH3), 1.78 (3H, s, eCH3), 5.12e5.15 (1H, m, ]
CHe), 3.40e3.42 (2H, d, eCH2e), 3.90 (3H, s, eCH3), 6.27e6.29 (1H,
d, H-3)7.97e7.99 (1H, d, H-4), 7.56e7.58 (1H,d,H-5), 7.06e7.08 (1H,
d, H-6); 13CNMR (DMSO): 20.93 (eCH3), 24.97 (eCH3),
(
), 154.79 (C-9), 159.77 (C-7), 160.88 (C-2).
C
131.31(
), 115.59(]CHe), 17.21(eCH2e), 55.78 (CH3Oe),
C
159.79 (C-2), 112.16 (C-3), 144.21 (C-4), 126.65 (C-5), 107.50 (C-6),
159.18 (C-7), 111.77 (C-8), 151.62 (C-9), 120.69 (C-10).
5.2.3.11. 4-Methyl-7-methyloxy coumarin (14). MS (m/z, %): 191.07
(Mþ þ H, 100). 1HNMR (DMSO): 2.41 (3H, s, eCH3), 3.87 (3H, s,