ORGANIC
LETTERS
2002
Vol. 4, No. 2
249-251
Total Synthesis of Spirotryprostatin B
via Asymmetric Nitroolefination
Trusar D. Bagul, Gingipalli Lakshmaiah, Takeo Kawabata, and Kaoru Fuji*
Institute for Chemical Research, Kyoto UniVersity, Uji, Kyoto 611-0011, Japan
Received November 4, 2001
ABSTRACT
A total synthesis of spirotryprostatin B was accomplished via asymmetric nitroolefination as a key step.
The asymmetric construction of molecules with quaternary
carbon stereocenters is a challenging and dynamic area,1 and
this is particularly true for the unabated isolation and
structural elucidation of various complex natural products
with these stereocenters. We have studied this subject2 and
have reported a protocol for creating quaternary asymmetric
carbon centers via the asymmetric nitroolefination.2a,b This
protocol has been applied2c-h to the synthesis of various
natural products with quaternary stereocenters: for example,
(-)-esermethole,2f (-)-pseudophrynaminol,2e,f (-)-horsifiline,2g
etc. We report here the total synthesis of spirotryprostatin B
(1), a potent antimitotic agent that was isolated from the
fermentation broth of Aspergillus fumigatus and has been
shown to inhibit progression of the mammalian cell cycle
in the G2/M phase at micromolar concentrations.3 The
synthetically intriguing structural features of 1 are the C-3
quaternary stereocenter of the spirooxindole, the spiro-
pyrrolidine with a diketopiperazine ring system and the
endocyclic conjugated C(8)-C(9) double bond along with
the pendent prenyl moiety. Recently, several successful
approaches have been reported for the total synthesis of 1
using the oxidative rearrangement of â-carbolines,4 1,3-
dipolar cycloaddition of azomethine ylides,5 and Pd-catalyzed
Heck insertion into a conjugated triene followed by an
intramolecular nucleophilic attack by amido nitrogen to the
resultant η3-allyl-Pd intermediate.6
Our strategy for the synthesis of 1 involves the enantio-
selective installation of a C-3 quaternary stereocenter at the
(1) (a) Fuji, K.; Chem. ReV. 1993, 93, 2037. (b) Corey, E. J.; Guzman-
Parez, A. Angew. Chem., Int. Ed. 1998, 37, 388. (c) Martin, S. F.
Tetrahedron 1980, 36, 419-460.
(3) (a) Cui, C.-B.; Kakeya, H.; Okada, G.; Onose, R.; Ubukata, M.;
Takahashi, I.; Isono, K.; Osada, H. J. Antibiot. 1995, 48, 1382-1384. (b)
Cui, C.-B.; Kakeya, H.; Osada, H. Tetrahedron 996, 52, 12651-12666.
(d) Cui, C.-B.; Kakeya, H.; Osada, H. Tetrahedron 1997, 53, 59-72. (e)
Cui, C.-B.; Kakeya, H.; Osada, H. J. Antibiot. 1996, 49, 832-833. (f) Cui,
C.-B.; Kakeya, H.; Osada, H. J. Antibiot. 1996, 49, 534-540.
(4) (a) Edmondson, S.; Danishefsky, S. J. Angew. Chem., Int. Ed. 1998,
37, 1138-1140. (b) Edmondson, S.; Danishefsky, S. J.; Sepp-Lorenzino,
L.; Rosen, N. J. Am. Chem. Soc. 1998, 121, 2147-2155. (c) Nussbaum, F.
V.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2000, 112, 2175-2178. (d)
Wang, H.; Ganesan, A. J. Org. Chem. 2000, 65, 4685-4693.
(2) (a) Fuji, K.; Node, M.; Nagasawa, H.; Naniwa, Y.; Terada, S. J. Am.
Chem. Soc. 1986, 108, 3855. (b) Fuji, K.; Node, M.; Nagasawa, H.; Naniwa,
Y.; Taga, T.; Machida, K.; Snatzke, G. J. Am. Chem. Soc. 1989, 111, 7921.
(c) Node, M.; Nagasawa, H.; Fuji, K. J. Am. Chem. Soc. 1987, 109, 7901.
(d) Node, M.; Nagasawa, H.; Fuji, K. J. Org. Chem. 1990, 55, 517. (e)
Fuji, K.; Kawabata, T.; Ohmori, T.; Node, M. Synlett 1995, 367. (f) Fuji,
K.; Kawabata, T.; Ohmori, T.; Shang, M.; Node, M. Heterocycles 1998,
47, 951. (g) Lakshmaiah, G.; Kawabata, T.; Shang, M.; Fuji, K. J. Org.
Chem. 1999, 64, 1699-1704.
10.1021/ol016999s CCC: $22.00 © 2002 American Chemical Society
Published on Web 12/27/2001