T. Ikeda et al. / Tetrahedron Letters 42 (2001) 2353–2356
2355
O
COOH
7α
8α
O
O
Diosgenin
c
7
a
b
HO
HO
HO
7β
9α
8β
c
c
13 : Diosgenin 14 : Cholesterol 15 : Glycyrrhetinic
Acid
10α
OH
O
OH
Cholesterol
O
O
O
6
OR
9
HO
HO
a
b
b
O
O
10β
12α
9β
HO
O
O
HO
c
OR
HO
HO
OH
HO
OH
HO
O
O
11α
a
d
HO
HO
11
OH
OH
Glycyrrhetinic Acid
30-methylester
R = 13
R = 14
R = 15
8α
10α
12α
8β
10β
12β
R = 13
R = 14
R = 15
12β
11β
d
Scheme 2. Reagents and conditions: (a) BF3·Et2O, CH2Cl2, rt; (b) ODS (90% MeOH); (c) 3% KOH/MeOH, reflux, 92–97%; (d)
3% LiOH/MeOH, reflux, 80–85%.
the same manner described above (entry 7) to afford an
a and b anomer mixture of chacotriosyl cholesterol 9
(55.8%, a:b=1:0.73) and chacotriosyl glycyrrehetic acid
11 (52.6%, a:b=1:0.56), respectively. The anomeric
mixtures of a- and b-chacotriosides were separated by
octadodecyl silica gel (ODS) column chromatography
using 90% MeOH to give a and b chacotriosides (7a,
7b, 9a, 9b, 11a, and 11b), respectively. Each glycoside
separated by ODS was deprotected in the usual manner
to give 8a, 8b, 10a, 10b, 12a, and 12b13 (Scheme 2).
2. (a) Encyclopedia of Contemporary Chinese Medical
Plants; Chi, S. Ed. (translation editor, Sugi, M.); Kogyo
Chosakai: Tokyo, 1980; pp. 79–87; (b) Chinese Drug
Dictionary; Koso New Medical College, Ed., Shanghai
Science and Technology Publishing Co.: Shanghai, 1978;
Vol. 1, pp. 630–631.
3. Nakamura, T.; Komori, C.; Lee, Y.-Y.; Hashimoto, F.;
Yahara, S.; Nohara, T.; Ejima, A. Biol. Pharm. Bull.
1996, 19, 564–566.
4. Ikeda, T.; Ando, J.; Miyazono, A.; Zhu, X.-H.; Tsuma-
gari, H.; Nohara, T.; Yokomizo, K.; Uyeda, M. Biol.
Pharm. Bull. 2000, 23, 364–365.
5. (a) Hsu, S.-H.; Tsai, T.-R.; Lin, C.-N.; Yen, M.-H.; Kuo,
K.-W. Biochem. Biophys. Res. Commun. 1996, 229, 1–5;
(b) Chang, L.-C.; Tsai, T.-R.; Wang, J.-J.; Lin, C.-N.;
Kuo, K.-W. Biochem. Biophys. Res. Commun. 1998, 242,
21–25.
The cytotoxicity of the obtained neosaponins (8a, 8b,
10a, 10b, 12a, and 12b) was tested with HCT116 and
PC-12 cell lines. Compound 8b showed cytotoxicity
{IC50: 2.66 mg/mL (HCT116); 1.99 mg/mL (PC-12)},
while the other neosaponins showed no cytotoxicity (>5
mg/mL).
6. (a) Ikeda, T.; Kajimoto, T.; Kinjo, J.; Nakayama, K.;
Nohara, T. Tetrahedron Lett. 1998, 39, 3513–3516; (b)
Ikeda, T.; Kinjo, J.; Kajimoto, T.; Nohara, T. Heterocy-
cles 2000, 52, 775–798.
In conclusion, facile preparation of an a-
L
-rhamnopy-
-glu-
ranosyl-(14)-[a- -rhamnopyranosyl-(12)]-a-
L
D
copyranosyl (chacotriosyl) trichloroacetimidate (6) has
been achieved (from the allyl glucoside to 6 by 4 steps
in 32% overall yield) in spite of the fact that the a
glycosides were more predominant than the b glyco-
sides in the oligoglycosylation. Since only the 8b
showed cytotoxicity, both the b stereochemistry of
chacotrioside and the steroidal aglycone moiety are
crucial for the cytotoxicity. To investigate futher struc-
ture-activity relationship, synthesis of more b-chacor-
tiosyl derivatives and bioassays are now in progress.
7. Compound 1 was readily prepared from 1,2,3,4,6-penta-
O-acetyl-D-glucose and allylalchohol in the presence of
BF3·Et2O. (a) Ogawa, T.; Beppu, K.; Nakabayashi, S.
Carbohydr. Res. 1981, 93, C6; (b) Ferrier, R. J.;
Furneaux, R. H. Methods Carbohydr. Chem. 1980, 8, 251.
8. (a) Jiang, L.; Chan, T.-H. J. Org. Chem. 1998, 63,
6035–6038; (b) Kurahashi, T.; Mizutani, T.; Yoshida, J.
J. Chem., Soc. Perkin Trans. 1 1999, 465–473.
9. (a) Schmidt, R. R. Advan. Carbohydr. Chem. Biochem.
1994, 50, 21–123; (b) Schmidt, R. R.; Michel, J. Angew.
Chem., Int. Ed. Engl. 1980, 39, 731–732.
Acknowledgements
10. Compound 6: [h]D25 +16.0° (c 0.43, CHCl3); lH (CDCl3,
500 MHz): 1.15 (3H, d, J=6.7 Hz, rha-6), 1.17 (3H, d,
J=6.1 Hz, rha-6), 1.21, 1.23 (18H, s, Piv), 1.97, 1.98,
2.04×2, 2.12×2 (18H, s, acetyl), 4.81 (1H, br s, rha-1),
4.91 (1H, d, J=1.8 Hz, rha-1), 5.65 (1H, dd, J=9.2, 9.8
Hz, glc-3), 6.42 (1H, d, J=3.7 Hz, glc-1a), 8.77 (1H, s,
-NH); FABMS (positive) m/z 1058 (M+Na)+.
This work was supported in part by a Grant-in-Aid for
Scientific Research (No. 11771387 to T.I.) from the
Ministry of Education, Science and Culture, Japan.
11. Nakayama, K.; Uoto, K.; Higashi, K.; Soga, T.;
Kusama, T. Chem. Pharm. Bull. 1992, 40, 1718–1720.
12. Schmidt, R. R.; Toepfer, A. Tetrahedron. Lett. 1991, 32,
3353–3356.
References
1. Studies in Plant Science, 6; Yang, C.-R.; Tanaka, O.,
Eds.; Advances in plant glycosides, chemistry and biol-
ogy. Elsevier: Amsterdam, 1999.
13. Selected spectroscopic data: 8a: [h]3D0−26.1° (c 0.11,
MeOH); lH (C5D5N): 0.70 (3H, d, J=5.5 Hz, H-27),