1
lated ∆ -pyrrolinium salts with the tert-butyl 3-oxopent-4-
1
5c
enoate (Scheme 1).
Scheme 1. Various Approaches Towards Maritidine
Figure 1
alkaloids.
. Representative structures of 5,10b-ethanophenanthridine
essentially two approaches. While the majority of approaches
used spiro-fused dienone 4 to elaborate to 1b, few strategies
have also employed the Pictet-Spengler cyclization of
From the preceding discussion, it is apparent that these
strategies employed stepwise generation of vicinal quaternary
and tertiary stereocenters along with the use of a cyclic
precursor for C-ring formation. Moreover, the Pictet-Spengler
cyclization route has produced only the dihydromaritidine
whose oxidative conversion to 1b has remained unsuccessful
to date.
3
-aryl-substituted hydroindole derivatives 5 into dihydro-
maritidine 6. Spiro-fused 4 has been synthesized employing
7
-10,14
phenolic oxidative para-para coupling
and photo-
1
1
chemical cyclization of norbelladine derivatives. Other
routes to 4 involve intramolecular Heck coupling or the
cyclization of an intermediate iron carbonyl complex. The
synthesis of 5 involved key reactions such as regioselective
reduction of 1-methyl-3,3-disubstituted pyrrolidine-2,5-
1
2
13
Our continuing interest in exploring the application of
nonstabilized azomethine ylides generated by sequential
double desilylation of R,R′-bis(trimethylsilylmethyl)alkyl-
1
6
17
1
5a
amines in the total synthesis of alkaloids with complex
architectures and the need to develop a concise and versatile
strategy to synthesize these types of alkaloids led us to
envisage the synthesis of 1 through an intramolecular 1,3-
dipolar cycloaddition of a nonstabilized azomethine ylide
dione, intramolecular ene cyclization of an appropriately
constructed acylnitroso olefin, or condensation of 3-ary-
1
5b
(
6) Maritidine: (a) Tani, S.; Kobayashi, N.; Fujiwara, H.; Shingu, T.;
Kato, A. Chem. Pharm. Bull. 1981, 29, 3381. (b) Hung, S.; Ma, G.; Sung,
G. Huaxue Xuebao 1981, 39, 529. (c) Ghosal, S.; Ashutosh, R.; Razdan, S.
Phytochemistry 1985, 24, 635. (d) Ma, G.; Li, H. Y.; Lu, C.; Yang, X.;
Hong, S. Heterocycles 1986, 24, 2089. (e) Ghosal, S.; Singh, S.; Srivastava,
R. S. Phytochemistry 1986, 25, 1975. (f) Kihara, M.; Koike, T.; Imakura,
Y.; Kia, K.; Shingu, T.; Kobayashi, S. Chem. Pharm. Bull. 1987, 35, 1070.
(AMY) as shown retrosynthetically in Scheme 2. This
proposed strategy originated from our recently accomplished
formal synthesis of the fused polycyclic 5,11-methanomor-
1
8
phanthridine skeleton of (()-pancracine.
(
g) Bastida, J.; Llabres, J. M.; Viladomat, F.; Codina, C.; Rubiralta, M.;
Feliz, M. Planta Med. 1988, 54, 524. Oxomaritidine: (h) Herrera, M. R.;
Brun, R.; Villadoma, F.; Codina, C.; Bastida, J. Planta Med. 2001, 67, 191
Regio- as well as stereochemical issues, the two important
aspects of this cycloaddition strategy, were evaluated at the
planning stage of the synthesis itself. The origin of the 5,10b-
ethanophenanthridine regiochemistry during cycloaddition,
.
(
(
7) Schwartz, M. A.; Holton, R. A. J. Am. Chem. Soc. 1970, 92, 1090
.
8) (a) Kotani, E.; Takeuchi, N.; Tobinaga, S. J. Chem. Soc., Chem.
Commun. 1973, 550. (b) Kotani, E.; Takeuchi, N.; Tobinaga, S. Tetrahedron
Lett. 1973, 29, 2735
9) Kita, Y.; Takada, T.; Gyoten, M.; Tohma, H.; Zenk, M. H.; Eichhorn,
J. J. Org. Chem. 1996, 61, 5857
10) (a) Ley, S. V.; Schucht, O.; Thomas, A. W.; Murray, P. J. J. Chem.
.
18
in contrast to the 5,11-methanophenanthridine skeleton, was
speculated based on the change in the LUMO energy of the
dipolarophile due to its conjugation with the aromatic ring
and ester moiety present on the same carbon. Cycloaddition
reaction of 8 was visualized to generate the vicinal quaternary
(
.
(
Soc., Perkin Trans. 1 1999, 1251. (b) Baxendale, I. R.; Deeley, J.; Griffiths-
Jones, C. M.; Ley, S. V.; Saaby, S.; Tranmer, G. K. Chem. Commun. 2006,
2
566
.
(
11) (a) Kametani, T.; Kohno, T.; Shibuya, S.; Fukumoto, K. Chem.
Commun. 1971, 14, 774. (b) Kametani, T.; Kohno, T.; Shibuya, S.;
Fukumoto, K. Tetrahedron 1971, 27, 5441.
(16) (a) Pandey, G.; Lakshmaiah, G.; Kumaraswamy, G. J. Chem. Soc.
Chem. Commun. 1992, 1313. (b) Pandey, G.; Lakshmaiah, G. Tetrahedron
Lett. 1993, 34, 4861.
(
(
(
12) Bru, C.; Thal, C.; Guillou, C. Org. Lett. 2003, 5, 1845.
13) Roe, C.; Stephenson, G. R. Org. Lett. 2008, 10, 189–192.
14) (a) Yamada, S.; Tomioka, K.; Koga, K. Tetrahedron Lett. 1976, 1,
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1999, 40, 6065. (d) Pandey, G.; Sahoo, A. K.; Gadre, S. R.; Bagul, T. D.;
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Sahoo, A. K. J. Org. Chem. 1998, 63, 760. (f) Pandey, G.; Lakshmaiah,
G.; Ghatak, A. Tetrahedron Lett. 1993, 34, 7301.
5
7. (b) Yamada, S.; Tomioka, K.; Koga, K. Tetrahedron Lett. 1976, 1, 61.
(
(
6
c) Tomioka, K.; Koga, K.; Yamada, S. Chem. Pharm. Bull. 1977, 25, 2681.
d) Tomioka, K.; Shimizu, K.; Yamada, S.; Koga, K. Heterocycles 1977,
, 1752.
(
15) (a) Wijnberg, J. B. P. A.; Speckamp, W. N. Tetrahedron 1978, 34,
2
579. (b) Keck, G. E.; Webb, R. R. J. Org. Chem. 1982, 47, 1302. (c)
Michael, J. P.; Howard, A. S.; Katz, R. B.; Zwane, M. I. Tetrahedron Lett.
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1
992, 33, 6023.
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