T. Zhou et al. / European Journal of Medicinal Chemistry 47 (2012) 86e96
95
[
a
]
ꢀ40.8ꢁ (c ¼ 0.0013, CH3Cl); HRMS for (Mþ þ Na): calcd m/z
1.06, 1.04, 1.00, 0.99 (each 3H, s, camphanoyl-CH3); [
a
]
ꢀ41.2ꢁ
D
D
755.2680, found: 755.2660.
(c ¼ 0.0052, CHCl3); HRMS for (Mþ þ Na): calcd m/z 743.2480, found:
743.2483.
6.1.7.8. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6,10-dimethoxy-1,2-
dihydropyrano[2,3-c]xanthen-7(1H)-one (15). 43% Yield (starting
6.1.7.14. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-trimethyl-6-methoxy-9-fluoro-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (21). 48% Yield (starting
from 10 mg of 35h); white solid; mp 177e178 ꢁC; 1H NMR
d 8.12
(1H, d, J ¼ 8.7 Hz, H-8), 6.84 (1H, dd, J ¼ 8.7, 2.4 Hz, H-9), 6.79 (1H, d,
J ¼ 4.5 Hz, H-1), 6.59 (1H, d, J ¼ 2.4 Hz, H-11), 6.26 (1H, s, H-5), 5.33
(1H, d, J ¼ 4.5 Hz, H-2), 3.92 (3H, s, OCH3-6), 3.77 (3H, s, OCH3-10),
2.40, 2.15, 1.95, 1.65 (each 2H, m, camphanoyl-CH2), 1.50, 1.42 (each
3H, s, CH3-3,3), 1.07, 1.06, 0.97, 0.93, 0.85, 0.81 (each 3H, s, cam-
from 45 mg of 35m); white solid; mp 204e205 ꢁC; 1H NMR
d 7.92
(1H, d, J ¼ 8.0 Hz, H-10), 7.28e7.36 (2H, m, H-9,11), 6.85 (1H, d,
J ¼ 4.4 Hz, H-1), 6.35 (1H, s, H-5), 5.40 (1H, d, J ¼ 4.4 Hz, H-2), 4.00
(3H, s, OCH3-6), 2.49, 2.19, 1.90, 1.68 (each 2H, m, camphanoyl-CH2),
1.56, 1.49 (each 3H, s, CH3-3,3), 1.14, 1.13, 1.04, 1.00, 0.90, 0.90 (each
phanoyl-CH3); [
calcd m/z 733.2860, found: 733.2874.
a
]
D ꢀ16.2ꢁ (c ¼ 0.0052, CH3Cl); HRMS for (Mþ þ 1):
3H, s, camphanoyl-CH3); [
a]
D ꢀ23.6ꢁ (c ¼ 0.0025, CHCl3); HRMS for
(Mþ þ Na): calcd m/z 743.2480, found: 743.2469.
6.1.7.9. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6,9-dimethoxy-1,2-
dihydropyrano[2,3-c]xanthen-7(1H)-one (16). 60% Yield (starting
from 20 mg of 35i); white solid; mp 168e170 ꢁC; ESIþ (m/z, %), 732
6.1.7.15. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-trimethyl-6-methoxy-8-fluoro-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (22). 80% Yield (starting
from 5 mg of 35n); white solid; mp 148e150 ꢁC; 1H NMR
d 7.44 (1H, t,
(Mþ, 100); 1H NMR
d
7.66 (1H, s, H-8), 7.21, 7.21 (each 1H, d,
J ¼ 8.7, 8.4 Hz, H-10), 7.01 (1H, d, J ¼ 8.4 Hz, H-11), 6.92 (1H, d,
J ¼ 8.7 Hz, H-9), 6.76 (1H, d, J ¼ 4.5 Hz, H-1), 6.26 (1H, s, H-5), 5.32 (1H,
d, J ¼ 4.5 Hz, H-2), 3.91 (3H, s, OCH3-6), 2.40, 2.12, 1.91, 1.67 (each 2H,
m, camphanoyl-CH2), 1.51, 1.42 (each 3H, s, CH3-3,3), 1.07, 1.05, 0.97,
J ¼ 9.2 Hz, H-10,11), 6.85 (1H, d, J ¼ 4.8 Hz, H-1), 6.32 (1H, s, H-5),
5.40 (1H, d, J ¼ 4.8 Hz, H-2), 4.00 (3H, s, OCH3-6), 3.88 (3H, s, OCH3-
9), 2.5, 2.20, 1.90, 1.70 (each 2H, m, camphanoyl-CH2), 1.57, 1.49
(each 3H, s, CH3-3,3), 1.14, 1.13, 1.03, 1.00, 0.90, 0.88 (each 3H, s,
0.93, 0.83, 0.83 (each 3H, s, camphanoyl-CH3); [
a
]D ꢀ17.1ꢁ (c ¼ 0.0035,
camphanoyl-CH3); [
a
]
D
ꢀ35.3ꢁ (c ¼ 0.0024, CHCl3); HRMS for
CHCl3), HRMS for (Mþ þ Na): calcd m/z 743.2480, found: 743.2476.
(Mþ þ 1): calcd m/z 733.2860, found: 733.2864.
6.1.7.16. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6-methoxy-10-bromo-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (23). 52% Yield (starting
6.1.7.10. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6,8-dimethoxy-1,2-
dihydropyrano[2,3-c]xanthen-7(1H)-one (17). 52% Yield (starting
from 35 mg of 35o); white solid; mp 159e160 ꢁC; 1H NMR
d 8.11 (1H,
from 10 mg of 35j); white solid; mp 155e156 ꢁC; 1H NMR
d
7.44 (1H,
d, J ¼ 8.4 Hz, H-8), 7.48 (1H, d, J ¼ 1.6 Hz, H-11), 7.44 (1H, dd,
J ¼ 8.4 Hz, H-9), 6.80 (1H, d, J ¼ 4.8 Hz, H-1), 6.32 (1H, s, H-5), 5.46
(1H, d, J ¼ 4.8 Hz, H-2), 3.97 (3H, s, OCH3-6), 2.45, 2.08, 1.90, 1.70 (each
2H, m, camphanoyl CH2),1.61,1.61 (each 3H, s, CH3-3,3), 1.46, 1.14, 1.12,
t, J ¼ 8.4, 8.4 Hz, H-10), 6.82 (1H, d, J ¼ 8.4 Hz, H-11), 6.80 (1H, d,
J ¼ 4.4 Hz, H-1), 6.75 (1H, d, J ¼ 8.4 Hz, H-9), 6.27 (1H, s, H-5), 5.36
(1H, d, J ¼ 4.4 Hz, H-2), 3.94, 3.93 (each 3H, s, OCH3-6.8), 2.50, 2.20,
1.90, 1.70 (each 2H, camphanoyl-CH2), 1.54, 1.46 (each 3H, s, CH3-
3,3), 1.13, 1.11, 1.03, 1.00, 0.88, 0.85 (each 3H, s, camphanoyl-CH3);
1.05, 1.04, 1.02 (each 3H, s, camphanoyl CH3); [
a]
D ꢀ25.3ꢁ (c ¼ 0.0035,
CHCl3); HRMS for (Mþ þ Na): calcd m/z 803.1679, found: 803.1691.
[
a
]
ꢀ131.7ꢁ (c ¼ 0.003, CHCl3); HRMS for (Mþ þ Na): calcd m/z
D
755.2680, found: 755.2671.
6.1.7.17. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-9-bromo-6-methoxy-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (24). 50% Yield (starting
6.1.7.11. 1R,2R-(ꢀ)-Dicamphanoyl-3,3,8-trimethyl-6,10-dimethoxy-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (18). 52% Yield (start-
from 10 mg of 35p); white solid; mp 159e160 ꢁC; 1H NMR
d 8.35 (1H,
d, J ¼ 2.8 Hz, H-8), 7.67 (1H, dd, J ¼ 8.8, 2.8 Hz, H-10), 7.20 (1H, d,
J ¼ 8.8 Hz, H-11), 6.81 (1H, d, J ¼ 4.4 Hz, H-1), 6.32 (1H, s, H-5), 5.47
(1H, d, J ¼ 4.4 Hz, H-2), 3.98 (3H, s, OCH3-6), 2.40, 2,10, 1.90, 1.60
(each 2H, m, camphanoyl-CH2), 1.56, 1.46 (each 3H, s, CH3-3,3), 1.14,
ing from 10 mg of 35q); white solid; mp 183e184 ꢁC; 1H NMR
d 6.85
(1H, d, J ¼ 4.8 Hz, H-1), 6.64 (1H, d, J ¼ 2.4 Hz, H-9), 6.53 (1H, d,
J ¼ 2.4 Hz, H-11), 6.30 (1H, s, H-5), 5.39 (1H, d, J ¼ 4.8 Hz, H-2), 3.99
(3H, s, OCH3-6), 3.81 (3H, s, OCH3-10), 2.84 (3H, s, CH3-8), 2.45, 2.20,
1.90, 1.70 (each 2H, m, camphanoyl CH2), 1.56, 1.48 (each 3H, s, CH3-
3,3), 1.13, 1.13, 1.04, 1.00, 0.91, 0.88 (each 2H, s, camphanoyl CH3);
1.12, 1.03, 1.02, 1.01, 0.77 (each 3H, s, camphanoyl-CH3); [
a]
D ꢀ13.0ꢁ
(c ¼ 0.004, CHCl3); HRMS for (Mþ þ Na): calcd m/z 803.1679, found:
803.1684.
[
a
]
ꢀ23.6ꢁ (c ¼ 0.0012, CHCl3); HRMS for (Mþ þ Na): calcd m/z
D
769.2836, found: 769.2835.
6.1.7.18. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6-methoxy-10-cyano-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (28). 80% Yield (starting
6.1.7.12. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6-methoxy-8-hydroxy-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (19). 30% Yield (starting
from 36 mg of 36); white solid; mp 164e165 ꢁC; 1H NMR
d 8.36 (1H,
d, J ¼ 8.0 Hz, H-8), 7.60 (1H, d, J ¼ 8.0 Hz, H-9), 7.55 (1H, s, H-11), 6.78
(1H, d, J ¼ 4.4 Hz, H-1), 6.35 (1H, s, H-5), 5.39 (1H, d, J ¼ 4.4 Hz, H-2),
3.99 (3H, s, OCH3-6), 2.50, 2.20, 1.90, 1.70 (each 2H, m, camphanoyl-
CH2), 1.56, 1.47 (each 3H, s, CH3-3,3), 1.12, 1.11, 1.05, 1.02, 0.98, 0.95
from 10 mg of 35k); white solid; mp 155e157 ꢁC; 1H NMR
d 12.94
(1H, s, OH-8), 7.43 (1H, t, J ¼ 8.0, 8.4 Hz, H-10), 6.78 (1H, d,
J ¼ 4.8 Hz, H-1), 6.74 (1H, d, J ¼ 8.0 Hz, H-9), 6.67 (1H, d, J ¼ 8.4 Hz,
H-11), 6.31 (1H, s, H-5), 5.36 (1H, d, J ¼ 4.8 Hz, H-2), 3.99 (3H, s,
OCH3-6), 2,45, 2.18, 1.90, 1.65 (each 2H, m, camphanoyl-CH2), 1.52,
1.45 (each 3H, s, CH3-3,3), 1.10, 1.09, 1.00, 0.96, 0.91, 0.88 (each 2H, s,
(each 3H, s, camphanoyl-CH3); [
a
]
ꢀ30.0ꢁ (c ¼ 0.0012, CHCl3);
D
HRMS for (Mþ þ Na): calcd m/z 750.2527, found: 750.2523.
camphanoyl-CH3); [
a
]
ꢀ62.5ꢁ (c ¼ 0.0018, CHCl3); HRMS for
6.1.7.19. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-dimethyl-6-methoxy-9-cyano-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (29). 65% Yield (starting
D
(Mþ þ Na): calcd m/z 741.2523, found: 741.2528.
from 30 mg of 37); white solid; mp 165e167 ꢁC; 1H NMR
d 8.59 (1H,
6.1.7.13. 1R,2R-(ꢀ)-Dicamphanoyl-3,3-trimethyl-6-methoxy-11-fluoro-
1,2-dihydropyrano[2,3-c]xanthen-7(1H)-one (20). 80% Yield (starting
s, H-8), 7.84 (1H, d, J ¼ 8.8 Hz, H-10), 7.37 (1H, d, J ¼ 8.8 Hz, H-11),
6.84 (1H, d, J ¼ 4.8 Hz, H-1), 6.39 (1H, s, H-5), 5.40 (1H, d, J ¼ 4.8 Hz,
H-2), 4.02 (3H, s, OCH3-6), 2.50, 2.10, 1.90, 1.70 (each 2H, m, cam-
phanoyl-CH2), 1.54, 1.50 (each 3H, s, CH3-3,3), 1.14, 1.12, 1.05,
from 45 mg of 35l); white solid; mp 183e184 ꢁC; 1H NMR
d 8.05 (1H,
d, J ¼ 8.0 Hz, H-8), 7.39 (1H, t, J ¼ 8.0, 8.4 Hz, H-9), 7.28 (1H, d,
J ¼ 8.4 Hz, H-10), 6.76 (1H, d, J ¼ 4.4 Hz, H-1), 6.36 (1H, s, H-5), 5.43
(1H, d, J ¼ 4.4 Hz, H-2), 4.01 (3H, s, OCH3-6), 2.51, 2.20, 1.92, 1.75 (each
2H, m, camphanoyl-CH2), 1.58, 1.48 (each 3H, s, CH3-3,3), 1.13, 1.13,
1.00, 0.93, 0.92 (each 3H, s, camphanoyl-CH3);
[a]
ꢀ51.0ꢁ
D
(c ¼ 0.0023, CH2Cl2); HRMS for (Mþ þ Na): calcd m/z 750.2527,
found: 750.2526.