Arch. Pharm. Chem. Life Sci. 2009, 342, 569–576
Antitumoractive Endoperoxides
573
(CH2), 28.0 (C15, CH2), 27.9 (C23, CH3), 25.6 (C12, CH2), 23.7 (C2,
CH2), 21.5 (CH2), 21.3 (Ac), 21.0 (CH2), 20.8 (C11, CH2), 19.0 (C29,
CH3), 18.1 (C6, CH2), 16.5 (C24, CH3), 16.5 (C26, CH3), 16.1 (C25,
CH3), 15.0 (C27, CH3) ppm; MS (ESI, MeOH) m/z: 633.2 [M + Na]+
(30%), 1243.2 [2 M + Na]+ (100%). Anal. calcd. for C39H62O5 (610.91):
C, 76.68; H, 10.23; found: C, 76.23; H, 9.97.
Anal. calcd. for C33H52O4 (512.76): C, 77.30; H, 10.22; found: C,
77.06; H, 10.12.
18-Glycyrrhetinic acid methyl ester 8
Following GP3 compound 8 (5.1 g, quant.) was obtained from
18b-glycyrrhetinic acid as a colorless solid; m.p.: 254–2588C (lit.
252–2548C [35]); [a]D = +141.28 (c = 4.8, CHCl3); Rf = 0.48 (silica gel,
hexane/ethyl acetate; 7:3); IR (KBr) m: 3614br, 2970s, 2955s,
2875m, 1726s, 1659s, 1466m, 1450m, 1364w, 1216m, 1189m,
3b-Acetylursolic acid methyl ester 6
Following GP2 and GP3 compound 6 (1.05 g, 94%) was obtained
from ursolic acid (1.00 g, 2.19 mmol) as a colorless solid; m.p.:
243–2468C (lit.: 243–2458C [33]); [a]D = +65.68 (c = 4.5; CHCl3); RF =
0.75 (silica gel, hexane/ethyl acetate, 8:2); IR (KBr) m: 2942s,
2868m, 1734s, 1458m, 1385m, 1371m, 1312w, 1244s, 1202m,
1187m, 1167w, 1150w, 1114w, 1073w, 1027m, 1006w cm– 1; 1H-
NMR (500 MHz, CDCl3) d: 5.23 (s, 1H, CH (12)), 4.48 (dd, J = 10.6,
5.5 Hz, 1H, CH (3)), 3.59 (s, 3H, OMe), 2.17 (d, J = 11.3 Hz, 1H, CH
(18)), 2.03 (s, 3H, Ac), 1.98 (ddd, J = 13.5, 13.4, 4.3 Hz, 1H, CHa (16)),
1.89 (dd, J = 8.7, 3.4 Hz, 2H, CH2 (11)), 1.85 (ddd, J = 13.6, 13.5, 4.3
Hz, 1H, CHa (15)), 1.69–1.55 (m, 6H, CH2 (22), CHa (1), CHb (16), CH2
(2)), 1.54–1.43 (m, 4H, CH (9), CHa (6), CHa (21), CHa (7)), 1.38-1.26
(m, 4H, CH (19), CHb (6), CHb (7), CHb (21)), 1.10–1.02 (m, 2H, CHb
(15), CHb (1)), 1.06 (s, 3H, CH3 (27)), 0.99–0.95 (m, 1H, CH (20)),
0.93 (s, 3H, CH3 (25)), 0.93 (d, J = 5.0 Hz, 3H, CH3 (30)), 0.87–0.83
(m, 1H, CH (5)), 0.86 (s, 3H, CH3 (23)), 0.85 (d, J = 5.4 Hz, 3H, CH3
(29)), 0.84 (s, 3H, CH3 (26)), 0.73 (s, 3H, CH3 (24)) ppm; 13C-NMR
(125 MHz, CDCl3) d: 178.0 (C28, C=O), 170.9 (Ac, C=O), 138.1 (C13,
C=CH), 125.4 (C12, HC=C), 80.9 (C3, HC-O), 55.3 (C5, CH), 52.8
(C18, CH), 51.4 (OMe, CH3), 48.0 (C17, Cquart.), 47.5 (C9, CH), 41.9
(C14, Cquart.), 39.5 (C8, Cquart.), 39.0 (C19, CH), 38.8 (C20, CH), 38.3
(C1, CH2), 37.6 (C4, Cquart.), 36.8 (C10, CH2), 36.6 (C22, Cquart.), 32.9
(C7, CH2), 30.6 (C21, CH2), 28.0 (C23, CH3), 28.0 (C15, CH2), 24.2
(C16, CH2), 23.5 (C27, CH3), 23.5 (C2, CH2), 23.3 (C11, CH2), 21.3
(Ac, CH3), 21.1 (C30, CH3), 18.2 (C6, CH2), 17.0 (C29, CH3), 17.0
(C24, CH3), 16.8 (C26, CH3), 15.5 (C25, CH3) ppm; MS (ESI, MeOH)
m/z: 513.2 [M + H]+ (40%), 535.5 [M + Na]+ (100%). Anal. calcd. for
C33H52O4 (512.76): C, 77.30; H, 10.22; found: C, 77.18; H, 10.16.
1
1136w, 1085w, 1040w, 992w cm–1; H-NMR (400 MHz, CDCl3) d:
5.65 (s, 1H, CH (12)), 3.67 (s, 3H, OCH3), 3.21 (dd, J = 10.8, 5.7 Hz,
1H, CH2 (3)), 2.78 (ddd, J = 13.3, 3.3, 3.3 Hz, 1H, CH2 (1)), 2.32 (s, 1H,
CH (9)), 2.06 (dd, J = 13.3, 3.8 Hz, 1H, CH (18)), 2.00 (m, 1H, CH2
(15)), 1.95 (m, 1H, CH2 (21)), 1.90 (dd, J = 13.8, 3.9 Hz, 1H, CH2 (19)),
1.83 (ddd, J = 14.3, 5.2, 5.2 Hz, 1H, CH2 (16)), 1.65 (m, 1H, CH2 (2)),
1.62 (m, 1H, CH2 (7)), 1.58 (m, 1H, CH2 (2)), 1.57 (m, 1H, CH2 (19)),
1.57 (m, 1H, CH2 (6)), 1.43 (m, 1H, CH2 (6)), 1.38 (m, 1H, CH2 (7)),
1.36 (m, 1H, CH2 (22)), 1.34 (s, 3H, CH3 (27)), 1.30 (m, 1H, CH2 (22)),
1.28 (m, 1H, CH2 (21)), 1.17 (m, 1H, CH2 (16)), 1.13 (s, 3H, CH3 (28)),
1.12 (s, 3H, CH3 (25)), 1.11 (s, 3H, CH3 (26)), 1.00 (m, 1H, CH2 (15)),
0.99 (s, 3H, CH3 (23)), 0.96 (m, 1H, CH2 (1)), 0.79 (s, 3H, CH3 (24)),
0.79 (s, 3H, CH3 (29)), 0.68 (m, 1H, CH (5)); 13C-NMR (125 MHz,
CDCl3) d: 200.0 (C11, C=O), 176.8 (C30, C=O), 169.0 (C13, Cquart.),
128.6 (C12), 78.8 (C3), 61.9 (C9), 55.1 (C5), 51.8 (OCH3), 48.5 (C18),
45.5 (C14, Cquart.), 44.1 (C20, Cquart.), 43.3 (C8, Cquart.), 41.2 (C19), 39.2
(C1), 39.2 (C4, Cquart.), 37.8 (C22), 37.2 (C10, Cquart.), 32.9 (C7), 31.9
(C17, Cquart.), 31.2 (C21), 28.6 (C29), 28.4 (C23), 28.2 (C28), 27.4
(C2), 26.6 (C16), 26.6 (C15), 23.5 (C27), 18.8 (C26), 17.6 (C6), 16.4
(C25), 15.6 (C24); MS (ESI, MeOH) m/z: 485.5 [M + H]+ (55%), 507.5
[M + Na]+ (12%), 539.1 [M + MeOH + Na]+ (100%). Anal. calcd. for
C31H48O4 (484.71): C, 76.82; H, 9.98; found: C, 76.55; H, 10.11.
Methyl 11-oxo-olean-2,12-dien-30-oate 9
Following GP6 compound 9 (1.51 g, quant.) was obtained from 8
(1.55 g, 3.20 mmol) as a colorless solid; m.p.: 182-1868C; [a]D
=
3b-Acetyloleanolic acid methyl ester 7
+204.68 (c = 3.42, CHCl3); Rf = 0.32 (silica gel, CHCl3/Et2O, 8:2); IR
(KBr) m: 3436m, 2957s, 2868m, 1723s, 1728s, 1655s, 1616m,
1465m, 1386m, 1360m, 1320m, 1279m, 1260m, 1218m, 1156m,
1089m, 1048w, 1029w cm– 1; 1H-NMR (400 MHz, CDCl3) d: 5.66 (s,
1H, CH (12)), 5.40 (ddd, J = 10.0, 5.8, 1.7 Hz, 1H, CH (2)), 5.34 (dd, J
= 10.0, 2.1 Hz, 1H, CH (3)), 3.67 (s, 3H, OCH3), 3.02 (dd, J = 17.4, 5.8
Hz, 1H, CH (1)), 2.39 (s, 1H, CH (9)), 2.07 (dd, J = 13.7, 4.2 Hz, 1H,
CH (18)), 2.00 (ddd, J = 13.7, 13.7, 5.0 Hz, 1H, CH2 (15)), 1.96 (m,
1H, CH2 (21)), 1.90 (m, 1H, CH2 (19)), 1.85 (ddd, J = 13.7, 13.7, 5.0
Hz, 1H, CH2 (16)), 1.68 (m, 1H, CH2 (7)), 1.64 (m, 1H, CH2 (1)), 1.60
(m, 1H, CH2 (19)), 1.53 (m, 1H, CH2 (6)), 1.46 (m, 1H, CH2 (6)), 1.40
(m, 1H, CH2 (7)), 1.37 (m, 1H, CH2 (22)), 1.34 (s, 3H, CH3 (27)), 1.32-
1.27 (m, 2H, CH2 (21), CH2 (22)), 1.22 (m, 1H, CH2 (16)), 1.14 (s, 3H,
CH3 (25)), 1.13 (s, 3H, CH3 (26)), 1.12 (s, 3H, CH3 (28)), 1.08 (m, 1H,
CH (5)), 0.99 (m, 1H, CH2 (15)), 0.94 (s, 3H, CH3 (23)), 0.89 (s, 3H,
CH3 (24)), 0.80 (s, 3H, CH3 (29));13C-NMR (125 MHz, CDCl3) d: 200.1
(C11, C=O), 176.9 (C30, C=O), 169.4 (C13, Cquart.), 137.0 (C3), 128.6
(C12), 121.9 (C2), 60.5 (C9), 51.8 (C5), 51.7 (OCH3), 48.4 (C18,
Cquart.), 45.3 (C14, Cquart.), 44.0 (C20, Cquart.), 43.2 (C8, Cquart.), 41.5
(C1), 41.2 (C19), 37.8 (C22), 36.2 (C4, Cquart.), 34.3 (C10, Cquart.), 31.9
(C7), 31.9 (C23), 31.8 (C17, Cquart.), 31.1 (C21), 28.5 (C29), 28.3
(C28), 26.5 (C16), 26.5 (C15), 23.3 (C27), 23.0 (C24), 18.7 (C6), 18.3
(C26), 16.1 (C25); MS (ESI, MeOH) m/z: 467.6 [M + H]+ (48%), 489.4
[M + Na]+ (8%), 521.0 [M + Na + MeOH]+ (100%). Anal. calcd. for
C31H46O5 (498.69): C, 79.78; H, 9.93; found: C, 79.68; H, 9.86.
Following GP2 and GP3 compound 7 (1.06 g, 96%) was obtained
from oleanolic acid (1.00 g, 2.19 mmol) as a colorless solid; m.p.:
219-2218C (lit.: 223–2258C [34]); [a]D = +69.38 (c = 3.8; CHCl3); RF =
0.75 (silica gel, hexane/ethyl acetate, 8:2); IR (KBr) m: 2939s,
1730s, 1471m, 1386m, 1364m, 1267m, 1240s, 1176w, 1163w,
1123w, 1096w, 1022m, 983w cm– 1; 1H-NMR (500 MHz, CDCl3) d:
5.26 (s, 1H, CH (12)), 4.47 (ddd, J = 8.4, 7.7, 1.7 Hz, 1H, CH (3)), 3.60
(s, 3H, OMe), 2.82 (d, J = 13.7 Hz, 1H, CH (18)), 2.02 (s, 3H, Ac), 1.95
(ddd, J = 14.6, 14.5, 3.4 Hz, 1H, CHa (16)), 1.88–1.84 (m, 2H, CH2
(11)), 1.69–1.23 (m, 14H, CH (9), CHa (1), CHa (19), CH2 (6), CH2 (7),
CHa (15), CHa (21), CH2 (22), CHb (16), CH2 (2)), 1.20-1.10 (m, 2H,
CHb (19), CHb (21)), 1.11 (s, 3H, CH3 (27)), 1.06-1.00 (m, 2H, CHb (15),
CHb (1)), 0.91 (s, 3H, CH3 (25)), 0.91 (s, 3H, CH3 (30)), 0.88 (s, 3H, CH3
(29)), 0.86–0.79 (m, 1H, CH (5)), 0.85 (s, 3H, CH3 (23)), 0.83 (s, 3H,
CH3 (26)), 0.71 (s, 3H, CH3 (24)) ppm; 13C-NMR (125 MHz, CDCl3) d:
178.2 (C28, C=O), 170.9 (Ac, C=O), 143.8 (C13, C=CH), 122.2 (C12,
HC=C), 80.9 (C3, HC-O), 55.3 (C5, CH), 51.5 (OMe, CH3), 47.5 (C9,
CH), 46.7 (C17, Cquart.), 45.8 (C19, CH2), 41.6 (C14, Cquart.), 41.3 (C18,
CH), 39.3 (C8, Cquart.), 38.1 (C1, CH2), 37.7 (C4, Cquart.), 36.9 (C10,
C
quart.), 33.7 (C21, CH2), 33.1 (C29, CH3), 32.5 (C7, CH2), 32.3 (C22,
CH2), 30.6 (C20, Cquart.), 28.0 (C23, CH3), 27.6 (C15, CH2), 25.9 (C27,
CH3), 23.6 (C30, CH3), 23.3 (C11, CH2), 23.3 (C2, CH2), 23.0 (C16,
CH2), 21.3 (Ac, CH3), 18.2 (C6, CH2), 16.8 (C24, CH3), 16.6 (C26, CH3),
15.3 (C25, CH3) ppm; MS (ESI, MeOH) m/z: 535.5 [M + Na]+ (100%).
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