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K.-H. Lim et al. / Tetrahedron Letters 47 (2006) 5037–5039
5039
O_
OCOCF3
+
N
+
N
TFAA
3
2
N
N
H
H
6
+
N
+
N
N
+
N
N
N
H
H
1
7
NaOH
SiO2, Me2CO, NH3
H
N
N
N
R
N
N
H
+
N
H
H
5
8 R = CH2COCH3
Scheme 2.
The formation of valparicine 1 is via the alternative
cleavage of the N-oxide to the iminium ion 7. This imin-
ium ion is in equilibrium with valparicine 1 in protic
media and can be trapped by NaBH4.16 Indeed when
valparicine 1 was dissolved in MeOH and NaBH4 was
added, pericine 2 was the sole product isolated. The
iminium ion 7 could also be trapped as the 3-acetonyl
derivative 8, on exposure of 1 to SiO2 and acetone, in
the presence of a trace quantity of concentrated
ammonia.
References and notes
1. Lim, K. H.; Kam, T. S. Org. Lett. 2006, 8, 1733–1735.
2. Kam, T. S.; Subramaniam, G. Tetrahedron Lett. 2004, 45,
3521–3524.
3. Kam, T. S.; Choo, Y. M. Helv. Chim. Acta 2004, 87, 991–
998.
4. Kam, T. S.; Choo, Y. M. Tetrahedron Lett. 2003, 44,
1317–1319.
5. Kam, T. S.; Subramaniam, G.; Lim, T. M. Tetrahedron
Lett. 2001, 42, 5977–5980.
6. Kam, T. S.; Lim, T. M.; Choo, Y. M. Tetrahedron 1999,
55, 1457–1468.
7. Kam, T. S. In Alkaloids: Chemical and Biological Perspec-
tives; Pelletier, S. W., Ed.; Pergamon: Amsterdam, 1999;
Vol. 14, pp 285–435.
8. Kam, T. S.; Subramaniam, G.; Sim, K. M.; Yoganathan,
K.; Koyano, T.; Toyoshima, M.; Rho, M. C.; Hayashi,
M.; Komiyama, K. Bioorg. Med. Chem. Lett. 1998, 8,
2769–2772.
9. HREIMS found m/z 276.1624 (calcd for C19H20N2,
276.1626).
10. Arens, H.; Borbe, H. O.; Ulbrich, B.; Stockigt, J. Planta
Med. 1982, 46, 210–214.
11. Kobayashi, J.; Sekiguchi, M.; Shimamoto, S.; Shigemori,
H.; Ishiyama, H.; Ohsaki, A. J. Org. Chem. 2002, 67,
6449–6455.
12. Kutney, J. P.; Nelson, V. R.; Wigfield, D. C. J. Am. Chem.
Soc. 1969, 91, 4278–4279.
13. Kutney, J. P.; Nelson, V. R.; Wigfield, D. C. J. Am. Chem.
Soc. 1969, 91, 4279–4280.
The above partial synthesis of apparicine 5 via the Po-
tier–Polonovski reaction has shown that pericine 2 can
be considered as a viable intermediate in the biogenetic
pathway to apparicine, deriving from stemmadenine 3
following deformylation or decarboxylation, and pre-
ceding one-carbon extrusion (Scheme 2). Such an alter-
native would be consistent with both the Kutney (one-
carbon extrusion preceding decarboxylation unlikely)13
and Scott (one-carbon extrusion and deformylation/
decarboxylation steps not necessarily synchronous)15 re-
sults. In addition it has also been shown that the new in-
dole valparicine 1 is in all probability biogenetically
related to pericine 2. It is, however, somewhat puzzling
that apparicine 5 was not detected among the many
alkaloids obtained from this plant, although both 2
and 5 have been previously found in A. subincanum.11
14. Ahond, A.; Cave, A.; Kan-Fan, C.; Langlois, Y.; Potier,
P. J. Chem. Soc., Chem. Commun. 1970, 517.
15. Scott, A. I.; Yeh, C. L.; Greenslade, D. J. Chem. Soc.,
Chem. Commun. 1978, 947–948.
16. Kompis, M.; Hesse, M.; Schmid, H. Lloydia 1971, 34,
269–291.
Acknowledgements
We would like to thank the University of Malaya,
IRPA, and the Academy of Sciences, Malaysia, for
financial support under the SAGA grant.