9
58
N.-C. Kong et al. / Tetrahedron Letters 50 (2009) 957–959
As described in Scheme 2, Diels–Alder reaction between maleic
anhydride and cyclopentadiene in solution of petroleum ether/
EtOAc at room temperature gave endo-bicyclo[2.2.1]hept-5-ene-
A
B
B
7
OH
2
,3-dicarboxylic anhydride (2) with the yield of 55%. Quinidine-
mediated desymmetrization of meso-anhydride (2) with MeOH in
toluene/CCl
at ꢀ55 °C for 60 h resulted in (+)-(1R,2S,5R,6S)-mono-
ester (3) with 92% yield and 97% ee.
in pyridine at 70 °C for 12 h gave (+)-(3S,4S)-iodo-lactone (4) in
3
O
4
6
–8
Treatment of 3 with iodine
O
9
9
,10
8
1
8% yield.
4 was then reduced by DIBAH in THF at ꢀ78 °C for
1
1
H- H COSY
h to produce corresponding (+)-(7S,9S)-iodo-cage (5) in 76%
HMBC
9
,11
yield.
Finally, hydrogenolysis of 5 with Bu SnH and AIBN in tol-
3
Figure 1. Selected 2D NMRcorrelations (A) and single-crystal X-ray structure(B) of1.
uene at 50 °C for 1.5 h afforded (+)-daphniacetal A (1) as colorless
crystal with 68% yield. The physical, spectroscopic, and spectro-
1
13
D
metric data ( H NMR, C NMR, [
a] , and HRMS) of the synthetic
material were well in consistence with those of the natural prod-
uct. Therefore, absolute configuration of the isolated 1 was deter-
mined as 1R,2S,3S,5R,6S,7S,9S.
and 101.0) were attributable to acetal or hemi-acetal groups. With
consideration of four degrees of unsaturation, it was assumed for
the presence of quateracyclic system in 1.
1
2
Compound 1 showed no antioxidant effects against H
2 2
O -in-
Comprehensive analysis of two-dimensional NMR data, includ-
duced impairment in PC12 cells.
1
1
ing the results of H– H COSY, HMQC, and HMBC experiments,
shown in Figure 1, enabled to establish planar structure of 1 as
an 8,11-dioxatetracyclo [4.3.1.2 1.
,5
4,7 1,6
0
]undecane with hydroxyl
Acknowledgments
group at C-7. The relative configuration of 1 was determined by
This research work was financially supported by the Natural
Science Foundation of PR China (project No. 20672120). Authors
were grateful to Professor Xun Gong, Kunming Institute of Botany,
Chinese Academy of Sciences (CAS), for the collection and identifi-
cation of the plant material.
NOESY experiments, and was confirmed by X-ray crystallographic
5
analysis (Fig. 1).
To further determine the absolute configuration of 1, asymmet-
ric total synthesis of 1 was applied. A retrosynthetic analysis
(Scheme 1) of the target molecule 1, involving the intermediate
3, led to the identification of maleic anhydride and cyclopentadi-
ene as the starting point for our synthesis. Additionally, cinchona
alkaloid-mediated opening of prochiral cyclic anhydride 2 in the
presence of methanol served as an effective stereo- and regioselec-
Supplementary data
6
tive operation.
References and notes
1.
(a) Suri, S. C. J. Org. Chem. 1993, 58, 4153–4154; (b) Coxon, J. M.; Fong, S. T.;
McDonald, D. Q. Tetrahedron Lett. 1991, 32, 7115–7118; (c) Marchand, A. P.;
Reddy, G. M.; Watson, W. H.; Kashyap, R. Tetrahedron 1990, 46, 3409–3418; (d)
Mehta, G.; Reddy, A. V. J. Org. Chem. 1987, 52, 460–462; (e) Mehta, G.; Rao, H. S.
P.; Reddy, K. R. J. Chem. Soc., Chem. Commun. 1987, 78–80; (f) Marchand, A. P.;
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1622–1625; (g) Mehta, G.; Rao, H. S. P. J. Chem. Soc., Chem. Commun. 1986, 472–
I
OH
COOMe
O
COOMe
COOH
O
O
O
5
3
473; (h) Fessner, W. D.; Prinzbach, H. Tetrahedron 1986, 42, 1797–1802; (i)
O
Mehta, G.; Nair, M. S. J. Am. Chem. Soc. 1985, 107, 7519–7524; (j) Singh, P. J. Org.
Chem. 1979, 44, 843–846; (k) Barborak, J. C.; Smith, E. C. J. Org. Chem. 1976, 41,
1433–1437; (l) Marchand, A. P.; Chou, T. C. Tetrahedron 1975, 31, 2655–2658;
O
O
+
O
(
m) Sasaki, T.; Eguchi, S.; Kiriyama, T.; Hiroaki, O. Tetrahedron 1974, 30, 2707–
O
2
O
2712; (n) Prinzbach, H.; Klaus, M. Angew. Chem., Int. Ed. Engl. 1969, 8, 276–278.
(a) Li, C. S.; Di, Y. T.; Mu, S. Z.; He, H. P.; Zhang, Q.; Fang, X.; Zhang, Y.; Li, S. L.;
Lu, Y.; Gong, Y. Q.; Hao, X. J. J. Nat. Prod. 2008, 71, 1202–1206; (b) Mu, S. Z.;
Wang, J. S.; Yang, X. S.; He, H. P.; Li, C. S.; Di, Y. T.; Wang, Y.; Zhang, Y.; Fang, X.;
Huang, L. J.; Hao, X. J. J. Nat. Prod. 2008, 71, 564–569; (c) Di, Y. T.; Liu, L. L.; Li, C.
S.; Zhang, Y.; Zhang, Q.; Mu, S. Z.; Sun, Q. Y.; Yang, F. M.; Liu, H. Y.; Hao, X. J.
Helv. Chim. Acta 2008, 91, 838–843;; (d) Tan, C. J.; Di, Y. T.; Wang, Y. H.; Wang,
Y.; Mu, S. Z.; Gao, S.; Zhang, Y.; Kong, N. C.; He, H. P.; Zhang, J. X.; Fang, X.; Li, C.
S.; Lu, Y.; Hao, X. J. Tetrahedron Lett. 2008, 49, 3376–3379; (e) Zhang, Y.; He, H.
P.; Di, Y. T.; Mu, S. Z.; Wang, Y. H.; Wang, J. S.; Li, C. S.; Kong, N.; Gao, S.; Hao, X.
J. Tetrahedron Lett. 2007, 48, 9104–9107; (f) Li, C. S.; Di, Y. T.; He, H. P.; Gao, S.;
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T.; He, H. P.; Wang, Y. S.; Li, L. B.; Lu, Y.; Gong, J. B.; Fang, X.; Kong, N. C.; Li, S. L.;
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P.; Yang, X. W.; Wang, Y. H.; Di, Y. T.; Lu, Y.; Chang, Y.; Hao, X. J. J. Nat. Prod.
2
.
Scheme 1. Retrosynthetic analysis of daphniacetal A (1).
O
5
6
O
(
a)
(b)
+
O
2
COOMe
1
COOH
O
O
2
O
3
2006, 69, 1065–1069; (i) Di, Y. T.; He, H. P.; Liu, H. Y.; Du, Z. Z.; Tian, J. M.; Yang,
1
0
X. W.; Wang, Y. H.; Hao, X. J. Tetrahedron Lett. 2006, 47, 5329–5331; (j) Di, Y. T.;
He, H. P.; Lu, Y.; Yi, P.; Li, L.; Wu, L.; Hao, X. J. J. Nat. Prod. 2006, 69, 1074–1076;
(k) Li, L.; He, H. P.; Di, Y. T.; Tian, J. M.; Hao, X. J. Helv. Chim. Acta 2006, 89, 1457–
1462; (l) Li, L.; He, H. P.; Di, Y. T.; Gao, S.; Hao, X. J. Tetrahedron Lett. 2006, 47,
6259–6262; (m) Di, Y. T.; He, H. P.; Li, C. S.; Tian, J. M.; Mu, S. Z.; Li, S. L.; Gao, S.;
Hao, X. J. J. Nat. Prod. 2006, 69, 1745–1748.
I
I
5 6
(c)
4
(d)
7
OH (e)
4
1
7
OH
COOMe
O
3
3
2
O
1
9
O
8
9
O
O
1
O
4
5
1
3.
(a) Kong, N. C.; He, H. P.; Wang, Y. H.; Mu, S. Z.; Di, Y. T.; Hao, X. J. Nat. Prod.
2
007, 70, 1348–1351; (b) Kong, N. C.; He, H. P.; Wang, Y. H.; Gao, S.; Di, Y. T.;
Scheme 2. Asymmetric synthesis of (+)-daphniacetal A (1). Reagents and condi-
tions: (a) in petrolum ether–EtOAc, rt, 4h, 55%; (b) quinidine–MeOH, in toluene/
CCl4, ꢀ55 °C, 60 h, 92%, 97% ee; (c) I2, in pyridine, 70 °C, 12 h, 88%; (d) DIBAH, in n-
Hao, X. J. Helv. Chim. Acta 2007, 90, 972–976.
2
0
4. Daphniacetal A (1): Colorless needles (ether), ½
a
ꢁ
+90.8 (c, 0.20, MeOH), mp
D
13
KBr
max
ꢀ1
1
149–151 °C; IR
k
:
3441(br, OH) cm
;
H
(500 MHz) and
C NMR
C
6
H14, ꢀ78 °C, 1 h, 76%; (e) Bu
3
SnH/AIBN, in toluene, 50 °C, 1.5 h, 68%.
(125 MHz) data see Table 1; EI-MS (70 ev) m/z: 168 (M+, 3), 151(18),