E. J. Banner et al. / Tetrahedron Letters 45 (2004) 4411–4414
4413
CO2CH3
CO2CH3
H3CO2C
b
CO2CH3
COCH(CH3)2
N
N
CO2CH3
N
CO2CH3
endo-boat
O
O
13
15
a
12
CO2CH3
H
CO2CH3
H
H3CO2C
b
CO2CH3
N
N
H
CO2CH3
N
H
CO2CH3
(H3C)2HCOC
exo-chair
O
O
14
16
Scheme 2. Reagents and conditions: (a) BSA, toluene, reflux, 7 d. (b) H2, 10% Pd/C, CH3OH.
13, and 14, over 10% palladium on carbon in methanol
for 7 h provided the decahydroquinolines, 15, and 16,
References and notes
1. Daly, J. W.; Tokuyama, T.; Habermehl, G.; Karle, I. L.;
Witkop, B. Justus Liebigs Ann. Chem. 1969, 729, 198.
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The Alkaloids; Cordell, G. A., Ed.; Academic: New York,
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M.; Spande, T. F. In Alkaloids: Chemical and Biological
Perspectives; Pelletier, S. W., Ed.; Pergamon: New York,
1999; Vol. 13, pp 1–161.
respectively, each in 92% yield. The structures of deca-
hydroquinolines 15 and 16 were both unequivocally
confirmed by X-ray crystallography.19 The crystal
structures showed the two diastereomers to be enantio-
mericallypure with the four stereocenters of the major
product 15 corresponding to the stereochemistryof cis-
275B.
As predicted, the major diastereomer of the intramo-
lecular Diels–Alder cyclization was the (2R)-(2a, 4ab,
5b, 8ab) cis-fused octahydroquinoline 13. The transition
state of this reaction for related triene systems has been
well studied.7;17 Presumably, 13 is formed via an endo-
stabilized boat transition-state (Scheme 2) in which the
pseudo-equatorial orientation of the C2 carbomethoxy
group provides the desired asymmetric induction at the
newlydeveloping stereocenters at C4a, C5, and C8a.
The minor diastereomer 14 is believed to be formed via
an exo-chair transition-state. The equatorial orientation
of the C2 carbomethoxygroup in the transition state
then leads to the observed chiralityinduced at C4a, C5,
and C8a.
3. Daly, J. W. J. Nat. Prod. 1998, 61, 162.
4. Spande, T. F.; Jain, P.; Garraffo, H. M.; Pannell, L. K.;
Yeh, H. J. C.; Daly, J. W.; Fukumoto, S.; Imamura, K.;
Tokuyama, T.; Torres, J. A.; Snelling, R. R.; Jones, T. H.
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5. (a) Warnick, J. E.; Jessup, P. J.; Overman, L. E.;
Eldefrawi, M. E.; Nimit, Y.; Daly, J. W.; Albuquerque,
E. X. Mol. Pharmacol. 1982, 22, 565; (b) Daly, J. W.;
Nishizawa, Y.; Padgett, W. L.; Tokuyama, T.; McClos-
key, P. J.; Waykole, L.; Schultz, A. G.; Aronstam, R. S.
Neurochem. Res. 1991, 16, 1207; (c) Daly, J. W. Braz.
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P., Brioni, J. D., Eds.; Wiley-Liss, 1998; p 253–270.
7. (a) Oppolzer, W.; Flaskamp, E. Helv. Chim. Acta 1977, 60,
This synthesis provides a versatile approach for the
construction of the 2,5-difunctional decahydroquinoline
ring system. The overall approach can be easily modified
to access the different stereoisomers of the decahydro-
quinoline cis-275B series of frog and ant alkaloids.
Studies directed toward the total synthesis of these
natural products and evaluation of their biological
activityare ongoing and will be reported in due course.
€
204; (b) Oppolzer, W.; Frostl, W.; Weber, H. P. Helv.
Chim. Acta 1975, 58, 593.
8. (a) Inubushi, Y.; Ibuka, T. Heterocycles 1977, 8, 633; (b)
Overman, L. E.; Jessup, P. J. Tetrahedron Lett. 1977, 1253;
(c) Overman, L. E.; Jessup, P. J. J. Amer. Chem. Soc. 1978,
100, 5179; (d) Ibuka, T.; Mori, Y.; Inubushi, Y. Chem.
Pharm. Bull. (Japan) 1978, 26, 2442.
9. (a) Ibuka, T.; Mori, Y.; Inubushi, Y. Tetrahedron Lett.
1976, 3169; (b) Oppolzer, W.; Fehr, C.; Warneke, J. Helv.
Chim. Acta 1977, 60, 48.
10. Habermehl, G.; Andres, H.; Miyahara, K.; Witkop, B.;
Daly, J. W. Justus Liebigs Ann. Chem. 1976, 1577.
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45, 5229.
SupplementaryData: Experimental procedures, spectral
data and elemental analyses are available for com-
pounds 9–16. The supplementarydata is available
online with the paper in ScienceDirect.
12. Mehta, G.; Praveen, M. J. Org. Chem. 1995, 60, 279.
13. Weymann, M.; Schultz-Kukula, M.; Kunz, H. Tetrahe-
dron Lett. 1998, 39, 7835.
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Acknowledgements
The authors thank the National Institute on Drug
Abuse (DA12703, MLT; DA14155, EJB) for the finan-
cial support of this research.