260
M. Kitajima et al. / Tetrahedron Letters 49 (2008) 257–260
7. Chaudhuri, P. K.; Thakur, R. S. J. Nat. Prod. 1993, 56,
of gloriosamine D was deduced to be that shown as for-
mula 5. The CD spectra of gloriosamines C (4) and D
(5) were similar to those of colchicine (1) and colchiciline
(6), indicating that their absolute configurations were
the same as those of 1 and 6.
1174–1176.
´
8. Blade-Font, A. Afinidad 1979, 36, 329–331.
ˇ
9. Santavy´, F.; Reichstein, T. Helv. Chim. Acta 1950, 33,
1606–1627.
10. von Muller, G.; Font, A. B.; Bardoneschi, R. Liebigs Ann.
Chem. 1963, 662, 105–113.
In conclusion, we have isolated and identified four new
colchicinoids from the aerial parts of G. rothschildiana.
Among them, gloriosamines A (2) and B (3) are the first
examples of natural colchicinoids having a substituent at
the C-4 position. Our preliminary biological evaluation
of 4-substituted colchicines demonstrated that 4-methoxy-
colchicine has significant cytotoxic activity against
human lung carcinoma cells A549 with an IC50 of
1.40 lM (colchicine: IC50 4.91 lM). Biological activity
of new colchicinoids, gloriosamines A (2) and B (3),
which also have a methoxy function on the C-4 position,
will be published in due course.
11. Kouroupis, P.; Hansen, H.-J. Helv. Chim. Acta 1995, 78,
1247–1277.
12. Heaney, H.; Newbold, A. J. Tetrahedron Lett. 2001, 42,
6607–6609.
13. Compound 9, amorphous, UV (EtOH) kmax nm: 348, 238.
1H NMR (400 MHz, CDCl3): 7.32 (1H, s, H-8), 7.29 (1H,
d, J = 11.0 Hz, H-11), 6.78 (1H, d, J = 11.0 Hz, H-12),
6.03 and 5.90 (each 1H, d, J = 1.5 Hz, –OCH2O–), 5.86
(1H, br d, J = 7.3 Hz, NH), 4.70 (1H, ddd, J = 12.0, 6.8,
6.8 Hz, H-7), 4.08, 3.97, 3.77 (each 3H, s, 3-OCH3, 4-
OCH3, 10-OCH3), 3.10 (1H, dd, J = 13.5, 6.0 Hz, H-5b),
2.23 (1H, dddd, J = 12.4, 12.4, 6.2, 6.2 Hz, H-6b), 2.03
(1H, ddd, J = 13.6, 13.6, 6.8 Hz, H-5a), 2.01 (3H, s, N-
COCH3), 1.76 (1H, ddd, J = 12.4, 12.4, 6.4 Hz, H-6a). EI-
MS m/z (%): 413 (M+, 67), 311 (100). HR-FAB-MS
(NBA/PEG) m/z: 414.1567 (MH+, calcd for C22H24NO7
414.1553). CD (c 0.23 mmol/L, MeOH, 25 °C) De (k nm):
0 (381), ꢁ5.3 (346), ꢁ1.2 (285), ꢁ3.9 (264), 0 (251), +6.6
(239), 0 (226), ꢁ4.5 (217), 0 (210).
References and notes
1. Ravelli, R. B. G.; Giant, B.; Curmi, P. A.; Jourdain, I.;
Lachkar, S.; Sobel, A.; Knossow, M. Nature 2004, 428,
198–202.
2. Pelletier, P. J.; Caventou, J. B. Liebigs Ann. Chem. 1924,
439, 59–75.
25
14. Gloriosamine B (3), amorphous, ½aꢀD ꢁ60 (c 0.10, CHCl3).
UV (EtOH) kmax nm: 351, 235, 219. FAB-MS (NBA) m/z:
430 (MH+). HR-FAB-MS (NBA/PEG) m/z: 430.1493
(MH+, calcd for C22H24NO8 430.1502). CD (c 0.17 mmol/
L, MeOH, 22 °C) De (k nm): 0 (393), ꢁ3.2 (347), ꢁ2.1
(316), ꢁ4.0 (291), 0 (252), +4.5 (232), 0 (219), ꢁ0.4 (215), 0
(212).
3. Mimaki, Y.; Ishibashi, N.; Komatsu, M.; Sashida, Y.
Shoyakugaku Zasshi 1991, 45, 255–260.
4. The aerial parts (1944 g) of Gloriosa rothschildiana were
extracted with hot MeOH to give the extract (81.6 g).
After washing with n-hexane, the MeOH extract was
chromatographed on a DIAION HP20. The fraction that
was eluted with 80% MeOH/H2O was purified by a
combination of column chromatographies to afford four
new alkaloids, gloriosamine A (2, 3.0 mg), gloriosamine B
(3, 1.5 mg), gloriosamine C (4, 20.2 mg), and gloriosamine
D (5, 1.0 mg).
24
15. Gloriosamine C (4), amorphous, ½aꢀD ꢁ156 (c 0.09,
CHCl3). UV (EtOH) kmax nm: 355, 245. IR (CHCl3) mmax
cmꢁ1: 3395, 2961, 2927, 2855, 1723. FAB-MS (NBA) m/z:
432 (MH+). HR-FAB-MS (NBA/PEG) m/z: 432.1683
(MH+, calcd for C22H26NO8 432.1658). CD (c 0.24 mmol/
L, MeOH, 25 °C) De (k nm): 0 (396), ꢁ7.7 (353), ꢁ4.2
(318), ꢁ8.7 (289), ꢁ6.0 (262), 0 (247), +12.2 (234), 0 (225),
ꢁ6.3 (217), 0 (208).
25
ˇ
´
ˇ
´
16. Poteˇsˇilova, H.; Dolejs, L.; Sedmera, P.; Santavy, F.
5. Gloriosamine A (2), amorphous, ½aꢀD ꢁ35 (c 0.10,
Collect. Czech. Chem. Commun. 1977, 42, 1571–1580.
CHCl3). UV (EtOH) kmax nm: 351, 235, 218. FAB-MS
(NBA) m/z: 414 (MH+). HR-FAB-MS (NBA/PEG) m/z:
414.1564 (MH+, calcd for C22H24NO7 414.1553). CD (c
0.45 mmol/L, MeOH, 25 °C) De (k nm): 0 (396), ꢁ7.0
(346), ꢁ3.5 (294), ꢁ6.8 (262), 0 (251), +11.7 (237), +1.5
(216).
25
17. Gloriosamine D (5), amorphous, ½aꢀD ꢁ95 (c 0.06,
CHCl3). UV (EtOH) kmax nm: 353, 244, 233. FAB-MS
(NBA) m/z: 401. HR-FAB-MS (NBA/PEG) m/z:
402.1568 (MH+, calcd for C21H24NO7 402.1553). CD (c
0.32 mmol/L, MeOH, 22 °C) De (k nm): 0 (392), ꢁ4.2
(349), ꢁ2.2 (317), ꢁ5.0 (289), ꢁ3.6 (269), ꢁ3.7 (264), 0
(244), +5.7 (234), 0 (224), ꢁ3.3 (217), 0 (210).
6. Ro¨sner, M.; Hsu, F.-L.; Brossi, A. J. Org. Chem. 1981, 46,
3686–3688.