3344
Y. Yamada et al. / Tetrahedron Letters 50 (2009) 3341–3344
Takayama, H. Chem. Pharm. Bull. 2008, 56, 870–872; (d) Kogure, N.; Someya, A.;
O
H
Urano, A.; Kitajima, M.; Takayama, H. J. Nat. Med. 2007, 61, 208–212; (e)
Kogure, N.; Ishii, N.; Kitajima, M.; Wongseripipatana, S.; Takayama, H. Org. Lett.
2006, 8, 3085–3088; (f) Kogure, N.; Nishiya, C.; Kitajima, M.; Takayama, H.
Tetrahedron Lett. 2005, 46, 5857–5861; (g) Kitajima, M.; Kogure, N.; Yamaguchi,
K.; Takayama, H.; Aimi, N. Org. Lett. 2003, 5, 2075–2078; (h) Kitajima, M.;
Urano, A.; Kogure, N.; Takayama, H.; Aimi, N. Chem. Pharm. Bull. 2003, 51,
1211–1214.
(i) Zn, AcOH
rt, 4 h
TMAD, n-Bu3P
H
O
Tr oc
NH
O
12
N
DMF
rt, 4 h, 81%
(ii) standing at
rt for 5 days
50%
OMe
15
10. The roots of Gelsemium elegans Benth. were collected in Phu Laung, Loei
Province, Thailand, and were identified by Dr. Sumphan Wongseripipatana. A
voucher specimen was deposited at the Faculty of Pharmaceutical Sciences,
Chulalongkorn University, Thailand. The roots of G. elegans (1353 g, dry weight)
were extracted with MeOH to give a MeOH extract (109.7 g). The MeOH extract
was dissolved in 20% MeOH/H2O and was extracted successively with n-
hexane, AcOEt, 5% MeOH/CHCl3, and n-BuOH. The 5% MeOH/CHCl3 extract
(6.33 g) was separated by SiO2 flash column chromatography with a CHCl3/
MeOH gradient to give seven fractions. The fraction eluted with 10% MeOH/
CHCl3 (164.5 mg) was purified by MPLC (3% MeOH/AcOEt and then 7% MeOH/
CHCl3) to give gelsevanillidine (1, 5.6 mg). Gelseoxazolidinine (2, 1.7 mg) was
obtained from the crude base (6.76 g) that was prepared from the roots of G.
elegans (600 g, dry weight) by a conventional method. The crude base was
separated by amino silica gel open column chromatography with a CHCl3/
MeOH gradient, and then with an n-hexane/CHCl3/MeOH gradient. The fraction
that was eluted with 70–100% CHCl3/n-hexane (552.5 mg) was purified by SiO2
flash column chromatography (CHCl3/MeOH gradient) and then by MPLC (5%
MeOH/AcOEt) to give gelseoxazolidinine.
R
O
O
H
14
H
Formalin
p-TsOH
20
20
H
O
H
O
21
21
N
N
H
N
O
N
Benzene
45 °C, 2.5 h
86%
OH
22
OMe
OMe
R=H: Gelselegine (16)
R=OAc: 14-Acetoxygelselegine (17)
14-Deacetoxy-
gelseoxazolidinine (3)
Scheme 2.
11. Gelsevanillidine (1): ½a D22
ꢀ
ꢁ 79:9 (c 0.24, MeOH); 1H and 13C NMR data, see Table
the modified Mitsunobu reaction [N,N,N0,N0-tetramethylazodicarb-
oxamide (TMAD), n-Bu3P, DMF] in 81% yield (Scheme 2). Removal
of the Nb-Troc group (Zn, AcOH) afforded a primary amine, which
was gradually cyclized at C-20 position to generate gelselegine
(16).17 Compound 16 was then treated with formalin in the pres-
ence of a catalytic amount of p-TsOH in benzene at 45 °C for
2.5 h to afford target molecule 318 in 86% yield. The 1H and 13C
NMR data and the CD spectral data of 3 resembled those of gels-
eoxazolidinine (2) well, except for the signals around C-14 position
bearing a b-acetoxy group. Thus, we propose that the structure of
gelseoxazolidinine is as shown in formula 2.
In conclusion, the novel structures of two gelsedine-related
oxindole alkaloids, gelsevanillidine (1) and gelseoxazolidinine (2),
isolated from G. elegans were elucidated by spectroscopic and
chemical methods. Gelsevanillidine is the first example of a mono-
terpenoid indole alkaloid with an additional vanillin residue, and
gelseoxazolidinine is a novel skeletal type alkaloid consisting of a
hexacyclic structure with an oxazolidine ring.
1; UV (MeOH) kmax nm (loge) 384 (3.57), 314 (4.05), 296 (sh, 4.01), 247 (sh,
4.02), 207 (4.46); IR (ATR)
m/z 461 (MH+); HRFABMS m/z 461.2075 (MH+, calcd for C27H29N2O5,
461.2076); CD (c 0.219 mmol/L, MeOH, 24 °C) (k nm) 0 (352), +2.81 (306),
m
max cmꢁ1 3263 (br), 2919, 1719, 1578, 1034; FABMS
D
e
0 (278), ꢁ8.15 (258), 0 (243), +3.64 (236), 0 (227), ꢁ23.34 (211).
12. Rankinidine used in this study was isolated from G. rankinii: Schun, Y.; Cordell,
G. A. J. Nat. Prod. 1986, 49, 806–808.
13. Takayama, H.; Tominaga, Y.; Kitajima, M.; Aimi, N.; Sakai, S. J. Org. Chem. 1994,
54, 4381–4385.
14. The possible mechanism for the oxidative cleavage of the enamine double
bond with excess m-CPBA is shown below.
O
H
O
H
O
Ar
HO
O
H
H
N
N
OH
O
Troc
Troc
7
Ar
HO
O
O
H
O
H
O
H
N
Acknowledgments
O
H
N
H
Troc
CHO
Troc
This work was supported by a Grant-in-Aid for Scientific Re-
search from the Japan Society for the Promotion of Science, the Re-
search Foundation for Pharmaceutical Sciences, and The Uehara
Memorial Foundation.
O
O
O
9
Ar
15. Du, X.; Dai, Y.; Zhang, C.; Lu, S.; Liu, Z. Acta Chim. Sin. 1982, 40, 1137–1141.
16. Gelseoxazolidinine (2): ½a D23
ꢀ
ꢁ 93:8 (c 0.07, MeOH); 1H and 13C NMR data, see
Table 2; UV (MeOH) kmax nm (loge) 284 (sh, 3.24), 256 (3.65), 209 (4.25); EIMS
References and notes
m/z (%) 428 (M+, 17), 398 (78), 367 (77), 121 (100); HREIMS m/z 428.1937 (M+,
calcd for C23H28N2O6, 428.1947); CD (c 0.369 mmol/L, MeOH, 24 °C)
0 (305), ꢁ4.46 (260), 0 (249), +7.81(236), 0 (222), ꢁ9.30 (212).
De (k nm)
1. Kitajima, M. J. Nat. Med. 2007, 61, 14–23.
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Diego, CA, 1997; Vol. 49,. Chapter 1, and references cited therein.
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1350.
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9. (a) Yamada, Y.; Kitajima, M.; Kogure, N.; Takayama, H. Tetrahedron 2008, 64,
7690–7694; (b) Kogure, N.; Kobayashi, H.; Ishii, N.; Kitajima, M.;
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(c) Kogure, N.; Ishii, N.; Kobayashi, H.; Kitajima, M.; Wongseripipatana, S.;
17. Lin, L.; Cordell, G. A.; Ni, C.; Clardy, J. Phytochemistry 1990, 29, 3013–3017.
18. 14-Deacetoxygelseoxazolidinine (3): 1H NMR (400 MHz, CDCl3) d 7.40 (1H, d,
J = 7.4 Hz, H-9), 7.27 (1H, ddd, J = 7.4, 7.4, 1.2 Hz, H-11), 7.09 (1H, ddd, J = 7.4,
7.4, 1.2 Hz, H-10), 6.92 (1H, d, J = 7.4 Hz, H-12), 4.57 (1H, d, J = 7.3 Hz, H-22),
4.38 (1H, d, J = 7.3 Hz, H-22), 4.21 (1H, dd, J = 12.0, 2.8 Hz, H-17), 4.20 (1H, br d,
J = 12.0 Hz, H-17), 4.01 (3H, s, Na–OMe), 3.59 (1H, d, J = 7.8 Hz, H-21), 3.57 (1H,
d, J = 6.4 Hz, H-3), 3.48 (br ddd, J = 9.2, 4.2, 3.1 Hz, H-5), 3.37 (1H, d, J = 7.8 Hz,
H-21), 2.75 (2H, overlapped, H-14, H-19), 2.62 (1H, br dddd, J = 9.2, 6.0, 2.8,
2.8 Hz, H-16), 2.38 (1H, br ddd, J = 11.2, 6.0, 2.5 Hz, H-15), 2.14 (1H, dd, J = 15.8,
3.1 Hz, H-6), 2.11 (1H, dd, J = 15.8, 4.2 Hz, H-6), 2.04 (1H, ddd, J = 15.5, 11.2,
6.4 Hz, H-14), 1.60 (1H, dq, J = 14.4, 7.5 Hz, H-19), 0.87 (3H, dd, J = 7.5, 7.5 Hz,
H3-18); 13C NMR (125 MHz, CDCl3) d 172.4 (C-2), 138.1 (C-13), 132.3 (C-8),
127.9 (C-11), 125.4 (C-9), 123.2 (C-10), 106.6 (C-12), 89.4 (C-22), 77.7 (C-20),
75.7 (C-21), 74.2 (C-3), 70.9 (C-5), 63.3 (Na–OMe, C-17), 55.9 (C-7), 38.4 (C-15),
37.6 (C-16), 37.5 (C-6), 26.7 (C-19), 23.0 (C-14), 9.2 (C-18); UV (MeOH) kmax nm
(log
HREIMS m/z 370.1892 (M+, calcd for C21H26N2O4, 370.1892); CD (c 0.351 mmol/
L, MeOH, 24 °C) (k nm) 0 (300), ꢁ1.46 (278), ꢁ5.73 (262), 0 (250), +11.08
(234), 0 (223), ꢁ19.82 (212).
e
) 257 (3.66), 208 (4.24); EIMS m/z (%) 370 (M+, 33), 340 (95), 309 (100);
D
e