84 Journal of Medicinal Chemistry, 2008, Vol. 51, No. 1
Yang et al.
14d, 1 equiv of AgCN powder (0.10 mmol) was needed. The
reaction mixture was stirred for 24 h at room temperature. After
workup, the resultant was partioned between water (2 mL) and
EtOAc. The crude product obtained from the organic phase was
purified by column chromatography over silica gel eluted with
petroleum/ethyl acetate/formic acid (3:1:0.1) to give 14a-14d,
respectively.
d, 16.2), 3.79 (18-NHCH2CH2OH, s), 3.70 (19-OMe, s), 3.55
(18-NHCH2CH2OH, s), 3.28 (H-3, br d, 3.9), 3.06 (H-5a, dd,
14.1, 6.1), 2.87 (H-6a, dd, 15.4, 6.1), 2.72 (H-9a, dd, 14.7, 8.5),
2.59 (H-9b, br d, 13.5), 2.13 (H-6b, m), 2.11 (OAc, s), 1.99
(H3-17, s), 1.85-1.68 (5H, m), 1.56 (H3-12, s). ESI-MS m/z:
476 [M + H]+, 951 [2M + H]+, 973 [2M + Na]+. IR: (cm-1
)
3407, 2951, 1740, 1711, 1649, 1535, 1444, 1279, 1244, 1207,
1167, 1072, 980.
1
Compound 14a. H NMR δH (in CDCl3): 7.26 (H-15, d,
1
Compound 15b. H NMR δH (in CDCl3): 7.21 (H-8, m),
11.5), 7.21 (H-8, m), 6.56 (H-14, dd, 15.0, 11.5), 5.92 (H-13,
d, 15.0), 3.72 (19-OMe, s), 3.32 (H-3, br d, 5.5), 3.09 (H-5a,
dd, 14.3, 6.5), 2.89 (H-6a, dd, 15.8, 6.5), 2.76 (H-9a, dd, 15.0,
8.8), 2.62 (H-9b, br d, 14.3), 2.41 (2H, q, 7.3), 2.13 (H-6b, br.t,
14.9), 1.96 (H3-17, s), 1.88-1.72 (5H, m), 1.60 (H3-12, s), 1.17
(3H, t, 7.7). ESI-MS m/z: 469 [M + Na]+, 915 [2M + Na]+.
IR: (cm-1) 3547, 3442, 2951, 1740, 1716, 1645, 1443, 1279,
1257, 1209, 1167, 1072, 993, 770.
6.98 (H-15, d, 11.5), 6.92 (NH, s), 6.51 (H-14, dd, 15.1, 11.5),
5.86 (H-13, d, 15.1), 4.11 (HO, 3H, br s), m), 3.72 (19-OMe,
s), 3.67 (18-NHC(CH2OH)3), 3.30 (H-3, br d, 3.6), 3.07 (H-5a,
dd, 14.6, 5.9), 2.89 (H-6a, dd, 15.3, 5.9), 2.74 (H-9a, dd, 15.3,
8.7), 2.61 (H-9b, m), 2.14 (H-6b, m), 2.13 (OAc, s), 1.99 (H3-
17, s), 1.86-1.71 (5H, m), 1.58 (H3-12, s). ESI-MS m/z: 536
[M + H]+, 1071 [2M + H]+, 1093 [2M + Na]+. IR: (cm-1
)
1
3400, 2926, 1740, 1713, 1630, 1518, 1444, 1371, 1279, 1244,
1209, 1167, 1072, 1051. HRESIMS m/z: 558.2300 [M + Na]+
(C27H37NaO10: calcd, 558.2315).
Compound 14b. H NMR δH (in CDCl3): 7.29 (H-15, d,
10.8), 7.21 (H-8, m), 6.55 (H-14, dd, 15.2, 10.8), 5.92 (H-13,
d, 15.2), 3.72 (19-OMe, s), 3.32 (H-3, br d, 5.0), 3.09 (H-5a,
dd, 13.4, 6.6), 2.88 (H-6a, dd, 16.4, 6.6), 2.76 (H-9a, dd, 15.0,
8.8), 2.61 (H-9b, br d, 14.3), 2.37 (2H, t, 7.6), 2.13 (H-6b, br.t,
14.9), 1.96 (H3-17, s), 1.86-1.28 (11H, m), 1.61 (H3-12, s),
0.89 (3H, t, 7.1). ESI-MS m/z: 511 [M + Na]+, 999 [2M +
Na]+. IR: (cm-1) 3460, 2955, 1736, 1710, 1686, 1641, 1439,
1275, 1232, 1159, 1076, 978, 750.
1
Compound 15c. H NMR δH (in CDCl3): 7.17 (H-8, m),
6.98 (H-15, d, 11.2), 6.48 (H-14, dd, 15.0, 11.2), 5.83 (H-13,
d, 15.0), 4.15 (18-NHCH2CO2H, m), 3.70 (19-OMe, s), 3.28
(H-3, br.s), 3.05 (H-5a, dd, 13.1, 5.9), 2.86 (H-6a, m), 2.71 (H-
9a, dd, 14.2, 8.6), 2.59 (H-9b, br d, 12.7), 2.11 (H-6b, m), 2.11
(OAc, s), 1.99-1.66 (5H, m), 1.56 (H3-17, s), 1.23 (H3-12, s).
ESI-MS m/z: 490 [M + H]+, 512 [M + Na]+, 979 [2M + H]+,
1001 [2M + Na]+. IR: (cm-1) 3415, 2951, 1740, 1709, 1659,
1525, 1443, 1371, 1279, 1244, 1207, 1167, 1072, 1018.
Compound 14c. 1H NMR δH (in CDCl3): 8.09 (2H, d, 7.6),
7.64 (1H, t, 8.0), 7.50 (2H, t, 8.0), 7.32 (H-15, d, 11.2), 7.24
(H-8, m), 6.61 (H-14, dd, 15.0, 11.2), 6.00 (H-13, d, 15.0), 3.72
(19-OMe, s), 2.88 (H-6a, dd, 14.8, 5.6), 2.67 (H-9a, dd, 14.4,
8.8), 2.58-2.50 (2H, m), 2.07 (H3-17, s), 2.21-1.69 (7H, m),
1.56 (H3-12, s). ESI-MS m/z: 517 [M + Na]+, 1011 [2M +
Na]+. IR: (cm-1) 3458, 2952, 1776, 1712, 1639, 1452, 1273,
1244, 1205, 1175, 1157, 1072, 1036, 1016, 999.
1
Compound 15d. H NMR δH (in CDCl3): 7.16 (H-8, m),
7.01 (H-15, d, 11.5), 6.48 (H-14, dd, 14.1, 11.5), 5.88 (H-13,
d, 14.1), 3.70 (19-OMe, s), 3.28 (H-3, br.s), 3.05 (H-5a, dd,
13.7, 5.9), 2.87 (H-6a, dd, 15.0, 5.8), 2.72 (H-9a, dd, 15.0, 9.0),
2.59 (H-9b, br d, 14.1), 2.13 (H-6b, m), 2.11 (OAc, s), 1.98
(H3-17, s), 1.89-1.68 (5H, m), 1.56 (H3-12, s). ESI-MS m/z:
489 [M + H]+, 977 [2M + H]+. IR: (cm-1) 3400, 2953, 1740,
1649, 1537, 1443, 1385, 1279, 1259, 1209, 1182, 1072, 1022,
953.
1
Compound 14d. H NMR δH (in CDCl3): 7.36-7.19 (6H,
m), 6.52 (H-14, dd, 15.2, 11.2), 5.87 (H-13, d, 15.2), 3.74 (19-
OMe, s), 3.64 (2H, br.s), 3.22 (br d, 3.2), 3.04 (H-5a, dd, 14.4,
6.2), 2.84 (H-6a, dd, 15.6, 6.2), 2.69 (H-9a, dd, 14.8, 8.8), 2.41
(H-9b, br d, 15.2), 2.04 (H-6b, m), 2.00 (H3-17, s), 1.87-1.64
(5H, m), 1.56 (H3-12, s). ESI-MS m/z: 565 [M + Na]+, 1107
[2M + Na]+. IR: (cm-1) 3435, 2951, 1738, 1708, 1643, 1493,
1439, 1279, 1257, 1209, 1165, 1092, 1016, 810.
Compound 15e. 1H NMR δH (in CDCl3): 7.54 (2H, d, 8.0),
7.32 (2H, t, 7.8), 7.18 (H-8, m), 7.11 (1H, t, 7.1), 7.02 (H-15,
d, 11.1), 6.53 (H-14, dd, 15.0, 11.1), 5.85 (H-13, d, 15.0), 3.70
(19-OMe, s), 3.29 (H-3, br d, 5.2), 3.06 (H-5a, dd, 14.0, 6.1),
2.88 (H-6a, dd, 15.5, 6.1), 2.74 (H-9a, dd, 15.1, 10.8), 2.60 (H-
9b, br d, 14.8), 2.14 (H-6b, m), 2.07 (OAc, s), 1.98 (H3-17, s),
1.85-1.70 (5H, m), 1.58 (H3-12, s). ESI-MS m/z: 508 [M +
H]+, 530 [M + Na]+, 1037 [2M + Na]+. IR: (cm-1) 3390,
2980, 1740, 1666, 1599, 1529, 1441, 1317, 1279, 1244, 1207,
1165, 1072, 1030.
General Procedure for Preparation of Compounds 11,
15a-15g. PAB (1; 0.10 mmol) was treated with 3 mL of SOCl2
at 40–50 °C for 20 min. After removal of the remaining SOCl2
under reduced pressure, the residue was dissolved into 1 mL of
anhydrous ethyl ether. The above solution of PAB chloride was
added to an anhydrous ethyl ether solution containing 5 equiv
of alcohol or amine, and the reaction was stirred at room
temperature for 1 h. After workup, the crude solid was purified
by silica gel column chromatography eluted with petroleum/
ethyl acetate/formic acid (3:1:0.1) or chloroform/methanol (10:
1) to give desired products 11 or 15a-15g, respectively.
Compound 11. 1H NMR δH (in CDCl3): 7.18 (H-8, m), 7.13
(H-15, d, 11.3), 6.51 (H-14, dd, 15.0, 11.3), 5.85 (H-13, d, 15.0),
4.17 (18-OCH2CH3, q, 7.0), 3.70 (19-OMe, s), 3.28 (H-3, br d,
5.4), 3.06 (H-5a, dd, 14.1, 6.2), 2.87 (H-6a, dd, 15.2, 6.2), 2.73
(H-9a, dd, 15.0, 8.8), 2.59 (H-9b, br d, 14.3), 2.13 (H-6b, m),
2.11 (OAc, s), 1.94 (H3-17, s), 1.85-1.69 (5H, m), 1.57 (H3-
12, s), 1.28 (18-OCH2CH3, t, 7.3). ESI-MS m/z: 483 [M + Na]+,
921 [2M + H]+, 943 [2M + Na]+. IR: (cm-1) 3454, 2953,
1741, 1708, 1643, 1444, 1369, 1277, 1232, 1207, 1165, 1099,
1072, 951.
Compound 15f. 1H NMR δH (in acetone-d6): 7.12-7.06 (3H,
m), 6.99 (1H, d, 11.0), 6.58-6.52 (2H, m), 6.12 (H-15, d, 15.1),
3.69 (19-OMe, s), 3.42 (1H, br.s), 3.32 (1H, br.s), 3.09 (H-5a,
dd, 14.2, 6.1), 2.82 (H-6a, dd, 15.5, 6.1), 2.70 (2H, d, 6.2), 2.31
(H-6b, m), 2.17 (OAc, s), 2.03 (H3-17, s), 1.96-1.67 (5H, m),
1.61 (H3-12, s). ESI-MS m/z: 524 [M + H]+, 546 [M + Na]+,
1069 [2M + Na]+. IR: (cm-1) 3390, 2953, 1740, 1716, 1647,
1603, 1539, 1508, 1444, 1317, 1279, 1232, 1209, 1165, 1165,
1072, 1030, 978.
1
Compound 15g. H NMR δH (in CDCl3): 7.26-6.87 (6H,
m), 6.58 (H-14, dd, 15.5, 11.1), 6.20 (H-13, d, 15.5), 3.69
(OCH3-19, s), 3.51 (H-3, br d, 5.1), 2.78-2.70 (4H, m), 2.13
(H-6b, m), 2.13 (OAc, s), 2.12 (H3-17, s), 1.45 (H3-12, s). ESI-
MS m/z: 523 [M + H]+. IR: (cm-1) 3425, 2951, 1740, 1713,
1647, 1524, 1497, 1454, 1317, 1242, 1196, 1082, 1032, 752.
1
Compound 15a. H NMR δH (in CDCl3): 7.18 (H-8, m),
Acknowledgment. Financial support of the National Natural
7.05 (H-15, d, 10.4), 6.49 (H-14, dd, 16.2, 10.4), 5.87 (H-13,
Science Foundation (Grant No. 30630072; 30572201; 30730103)