5244
R. Tanaka et al. / Bioorg. Med. Chem. 17 (2009) 5238–5246
J = 2.1 Hz, H-21), 5.82 (1H, s, H-4), 6.49 (1H, d, J = 15.8 Hz, H-6),
6.54 (1H, d, J = 15.7 Hz, H-2), 6.94 (1H, d, J = 8.2 Hz, H-500), 7.05
(1H, d, J = 1.8 Hz, H-200), 7.11 (1H, d, J = 7.6 Hz, H-50), 7.12 (1H, s,
H-20), 7.13 (1H, dd, J = 8.2, 1.8 Hz, H-600), 7.16 (1H, d, J = 7.6 Hz, H-
60), 7.59 (1H, d, J = 15.7 Hz, H-1), 7.61 (1H, d, J = 15.8 Hz, H-7);
13C NMR d 41.6 (O@C–CH2–C@O), 80.4 (C-21), 101.5 (C-4), 109.6
(C-200), 111.6 (C-20), 114.9 (C-500), 120.8 (C-60), 121.7 (C-6), 123.0
(C-50 and C-600), 124.4 (C-2), 127.5 (C-100), 134.4 (C-10), 139.2 (C-
1), 140.7 (C-40), 141.2 (C-7), 146.8 (C-300), 148.0 (C-400), 151.2 (C-
30), 164.5 and 165.5 (O@C–CH2–C@O), 181.6 (C-3), 184.6 (C-5).
HRMS (FAB) calcd for C55H72O10Na [M+Na]+, 915.5023; found,
chromatography (hexane/EtOAc = 4:1–2:1) to afford compound 11
(12.1 mg, 17%) and compound 13 (27.0 mg, 40%). Compound 11,
mp 168–171 °C; [a]
D + 8.1 (c 0.096); 1H NMR d 2.79 and 2.95 (each
2H, t, J = 7.1 Hz, –O–CO–CH2–CH2–CO–O–), 4.50 (2H, s, H-7), 4.71
(1H, t, J = 2.4 Hz, H-21), 6.56 (1H, s, H-3), 7.89 (1H, s, H-6). 13C
NMR d 28.8 and 29.3 (O@C–CH2–CH2–C@O), 60.7 (C-7), 79.1 (C-
21), 113.2 (C-3), 141.0 (C-5), 147.9 (C-6), 167.8 (C-2), 169.7 and
171.5 (O@C–CH2–CH2–C@O), 172.8 (C-4). HRMS (FAB) calcd for
C41H60O8Na [M+Na]+ m/z 703.4186; found, 703.4184. Compound
13, mp 130–133 °C; [a]
+71.1 (c 0.092); 1H NMR d 2.68 (4H, td,
D
J = 4.4, 1.4 Hz, O–CO–CH2–CH2–CO–O–), 2.72 (4H, td, J = 4.8,
1.4 Hz, –O–CO–CH2–CH2–CO–O–), 4.70 and 4.71 (each 1H, t,
J = 2.8 Hz, H-21, H-210), 4.96 (2H, s, H-7), 6.51 (1H, s, H-3), 7.85
(1H, s, H-6). 13C NMR d 29.3 and 29.4 (O@C–CH2–CH2–C@O), 61.5
(C-7), 78.9 and 79.1 (C-21 and C-210), 111.3 (C-3), 138.1 (C-6),
145.8 (C-5), 162.6 (C-2), 171.4, 171.7 and 176.4 (O@C–CH2–CH2–
C@O), 173.9 (C-4). HRMS (FAB) calcd for C76H114O12Na [M+Na]+,
1241.8208; found, 1241.8215.
915.5030. Compound 9: mp 173–176 °C; [a]
+ 0.3 (c 0.081); 1H
D
NMR d 3.69 (4H, d, J = 1.6 Hz, O@C–CH2–C@O), 3.88 (6H, s, C-30
and C-300 OMe), 4.80 (2H, t, J = 2.1 Hz, H-21 and H-210), 5.85 (1H,
s, H-4), 6.56 (2H, d, J = 15.8 Hz, H-2 and H-6), 7.11 (2H, d,
J = 7.1 Hz, H-50 and H-500), 7.12 (2H, s, H-20 and H-200), 7.16 (2H, d,
J = 7.1 Hz, H-60 and H-600), 7.62 (2H, d, J = 15.8 Hz, H-1 and H-7));
13C NMR d 41.6 (O@C-CH2-C@O), 80.4 (C-21, C-210), 101.9 (C-4),
111.6 (C-20, C-200), 120.9 (C-60, C-600), 123.1 (C-50, C-500), 124.4 (C-
2, C-6), 134.2 (C-10, C-100), 139.9 (C-1, C-7), 140.9 (C-40, C-400),
151.2 (C-30, C-300), 164.5 (O@C–CH2–C@O), 165.5 (O@C–CH2–
C@O), 183.0 (C-3, C-5). HRMS (FAB) calcd for C89H124O14Na
[M+Na]+, 1439.8889; found, 1439.8882.
3.2.14. Compounds 12 and 14
Compounds 12 (30%) and 14 (19%) were synthesized from com-
pound 2 succinic acid similarly to compounds 11 and 13. Com-
pound 12, mp 138–140 °C; [
a
]
D
+ 4.3 (c 0.10); 1H NMR d 2.79
and 2.95 (each 2H, t, J = 6.8 Hz, O@C–CH2–CH2–C@O), 4.50 (2H, s,
H-7), 4.71 (1H, t, J = 2.1 Hz, H-21), 6.57 (1H, s, H-3), 7.89 (1H, s,
H-6). 13C NMR d 28.8 and 29.3 (O@C–CH2–CH2–C@O), 60.8 (C-7),
79.0 (C-21), 113.2 (C-3), 141.0 (C-5), 147.9 (C-6), 167.7 (C-2),
169.7 and 171.5 (O@C–CH2–CH2–C@O), 172.8 (C-4); HRMS (FAB)
calcd for C41H60O8Na [M+Na]+ m/z 703.4186; found, 703.4192.
3.2.12. Compounds 8 and 10
Compounds 8 (137.0 mg, 49%) and 10 (52.1 mg, 20%) were ob-
tained from compound 2 malonic acid (200 mg, 0.37 mmol). The
reaction method employed was similar to that of compounds 7
and 8. Compound 8, mp 150–153 °C; [a]
+6.8 (c 0.138); 1H NMR
D
d 3.69 (2H, d, J = 1.6 Hz, O@C–CH2–C@O), 3.87 (3H, s, C-30 OMe),
3.95 (3H, s, C-300 OMe), 4.80 (1H, t, J = 2.3 Hz, H-21), 5.82 (1H, s,
H-4), 6.49 (1H, d, J = 15.8 Hz, H-6), 6.54 (1H, d, J = 15.8 Hz, H-2),
6.93 (1H, d, J = 8.3 Hz, H-500), 7.06 (1H, d, J = 1.8 Hz, H-200), 7.10
(1H, d, J = 7.0 Hz, H-50), 7.11 (1H, s, H-20), 7.12 (1H, dd, J = 8.3,
1.8 Hz, H-600), 7.16 (1H, d, J = 7.0 Hz, H-60), 7.59 (1H, d, J = 15.8 Hz,
H-1), 7.61 (1H, d, J = 15.8 Hz, H-7); 13C NMR d 41.6 (O@C–CH2–
C@O), 80.4 (C-21), 101.6 (C-4), 109.6 (C-200), 111.7 (C-20), 114.8
(C-500), 120.7 (C-60), 121.7 (C-6), 123.0 (C-600), 123.1 (C-50), 124.4
(C-2), 127.5 (C-100), 134.4 (C-10), 139.2 (C-1), 140.7 (C-40), 141.2
(C-7), 146.8 (C-300), 148.0 (C-400), 151.2 (C-30), 164.5 and 165.5
(O@C–CH2–C@O), 181.5 (C-3), 184.6 (C-5). HRMS (FAB) calcd for
C55H72O10Na [M+Na]+, 915.5023; found, 915.5031. Compound 10,
Compound 14, mp 124–126 °C; [
a
]
D
ꢁ41.2 (c 0.116); 1H NMR d
2.69 (4H, td, J = 4.1, 1.1 Hz, O@C–CH2–CH2–C@O), 2.73 (4H, td,
J = 4.3, 1.6 Hz, O@C–CH2–CH2–C@O), 4.70 and 4.71 (each 1H, t,
J = 1.9 Hz, H-21, H-210), 4.95 (2H, s, H-7), 6.51 (1H, s, H-3), 7.85
(1H, s, H-6). 13C NMR d 29.2 and 29.4 (O@C–CH2–CH2–C@O), 61.5
(C-7), 78.9 and 79.1 (C-21 and C-210), 111.3 (C-3), 138.1 (C-6),
145.9 (C-5), 162.6 (C-2), 171.4, 171.7 and 176.2 (O@C–CH2–CH2–
C@O), 173.9 (C-4). HRMS (FAB) calcd for C76H114O12Na [M+Na]+,
1241.8208; found, 1241.8203.
3.2.15. Compound 15
To a solution of compound 1 succinic acid (40.6 mg, 0.07 mmol)
in DMF (2 mL) were added quercetin (23.3 mg, 0.08 mmol),
WSCꢂHCl (19.7 mg, 0.09 mmol), and HOBt (10.7 mg, 0.07 mmol)
and the mixture was stirred at 60 °C for 1 h under nitrogen atmo-
sphere. To the reaction mixture was added water and the whole
was extracted with EtOAc. The organic layer was washed with
brine, dried over magnesium sulfate, and concentrated in vacuo.
The residue was purified with silica gel column chromatography
(hexane/EtOAc = 4:1–1:1) to give compound 15 (40.5 mg, 86%),
mp 159–162 °C; [
a]
+ 4.1 (c 0.139); 1H NMR d 3.69 (4H, d,
D
J = 1.1 Hz, O@C–CH2–C@O), 3.88 (6H, s, C-30 and C-300 OMe), 4.80
(2H, t, J = 2.1 Hz, H-21 and H-210), 5.84 (1H, s, H-4), 6.56 (2H, d,
J = 15.8 Hz, H-2 and H-6), 7.11 (2H, d, J = 8.3 Hz, H-50 and H-500),
7.13 (2H, d, J = 1.8 Hz, H-20 and H-200), 7.17 (2H, dd, J = 8.3, 1.8 Hz,
H-60 and H-600), 7.61 (2H, d, J = 15.8 Hz, H-1 and H-7); 13C NMR d
41.6 (O@C–CH2–C@O), 80.4 (C-21, C-210), 101.9 (C-4), 111.7 (C-20,
C-200), 120.9 (C-60, C-600), 123.0 (C-50, C-500), 124.4 (C-2, C-6), 134.2
(C-10, C-100), 139.8 (C-1, C-7), 140.9 (C-40, C-400), 151.2 (C-30, C-300),
164.5 (O@C–CH2–C@O), 165.5 (O@C–CH2–C@O), 183.0 (C-3, C-5).
HRMS (FAB) calcd for C89H124O14Na [M+Na]+, 1439.8889; found,
1439.8895.
mp 187–190 °C; [a]
+ 52.3 (c 0.065); 1H NMR d 2.92 and 2.96
D
(each 2H, m, O@C–CH2–CH2–C@O), 4.80 (1H, t, J = 2.1 Hz, H-21),
6.19 (1H, d, J = 1.9 Hz, H-6), 6.27 (1H, d, J = 1.9 Hz, H-8), 7.12 (1H,
d, J = 8.3 Hz, H-50), 7.92 (1H, d, J = 2.1 Hz, H-20), 7.94 (1H, dd,
J = 8.3, 2.1 Hz, H-60); 13C NMR d 29.7 and 30.2 (O@C–CH2–CH2–
C@O), 80.8 (C-21), 94.1 (C-8), 98.9 (C-6), 103.4 (C-4a), 117.8
(C-50), 122.4 (C-20), 123.1 (C-10), 127.0 (C-60), 135.5 (C-3), 137.4
(C-30), 144.2 (C-2), 150.1 (C-40), 156.5 (C-8a), 160.9 (C-5),
162.7 (C-7), 171.7 and 174.0 (O@C–CH2–CH2–C@O), 174.8 (C-4);
HRMS (FAB) calcd for C50H65O11 [M+1]+, 841.4527; found, 841.4529.
3.2.13. Compounds 11 and 13
To a solution of compound 1 succinic acid (60.6 mg, 0.11 mmol)
in dimethylformamide (DMF) (2 mL) were added kojic acid
(16.8 mg, 0.12 mmol), 1-ethyl-3-(dimethylaminopropyl)carbodi-
imide hydrochloride (WSCꢂHCl, 24.8 mg, 0.13 mmol), and 1-
hydroxybenzotriazole (HOBt) (16.5 mg, 2 mmol) and the mixture
was stirred at 60 °C for 1 h under nitrogen atmosphere. To the reac-
tion mixture was added satd-sodium hydrogen carbonate aqueous
and the whole was extracted with EtOAc. The organic layer was
washed with brine, dried over magnesium sulfate, and concen-
trated in vacuo. The residue was purified by silica gel column
3.2.16. Compound 16
Compound 16 (50%) was synthesized from compound 2 succinic
acid similarly to compound 15. Mp 207–210 °C; [
a
]
ꢁ22.2 (c
D
0.115); 1H NMR d 2.92 and 2.95 (each 2H, m, O@C–CH2–CH2–
C@O), 4.80 (1H, t, J = 2.3 Hz, H-21), 6.20 (1H, br s, H-6), 6.29 (1H,
br s, H-8), 7.13 (1H, d, J = 8.8 Hz, H-50), 7.92 (1H, d, J = 1.8 Hz,