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4
02; Angew. Chem. Int. Ed. 1998, 37, 388; R. Noyori, Asymmetric
Total Synthesis of Diazonamide A**
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2] For reviews of the palladium-catalyzed asymmetric allylic alkylation,
see B. M. Trost, D. L. Van Vranken, Chem. Rev. 1996, 96, 395; A.
Heumann, M. Reglier, Tetrahedron 1995, 51, 975; T. Hayashi in
Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH, New York,
K. C. Nicolaou,* Marco Bella, David Y.-K. Chen,
Xianhai Huang, Taotao Ling, and Scott A. Snyder
[
In 1991, Fenical and co-workers reported structure 1 for
1
993; M. Sawamura, Y. Ito, Chem. Rev. 1992, 92, 857; J. C. Fiaud, In
diazonamide A, a marine natural product which had been
Metal-Promoted Selectivity in Organic Synthesis (Eds.: M. Graziani,
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[1]
isolated from the colonial ascidian diazona angulata.
A
[
3] a) B. M. Trost, G. M. Schroeder, J. Am. Chem. Soc. 1999, 121, 6759;
b) B. M. Trost, R. Radinov, E. M. Grenzer, J. Am. Chem. Soc. 1997,
Me
Me
N
Me
Me
H
1
19, 7879.
H
N
N
[
4] S.-L. You, X.-L. Hou, L.-X. Dai, X.-Z. Zhu, Org. Lett. 2001, 3, 149, and
references therein; T. Hayashi, K. Kanehira, T. Hagihara, M. Kumada,
J. Org. Chem. 1988, 53, 113.
H2N
N
A
Cl
O
O
O
B
Cl
O
[
[
[
5] K. Ishihara, S. Nakamura, M. Kaneeda, H. Yamamoto, J. Am. Chem.
Soc. 1996, 118, 12854 ± 12855.
6] T. Ohwada, K. Okabe, T. Ohta, K. Shudo, Tetrahedron 1990, 46, 7539 ±
E
G
C
F
O
NH
D
HO OH
7
555.
1
: original structure of diazonamide A
7] W. Vaccaro, C. Amore, J. Berger, R. Burrier, J. Clader, H. Davis, M.
Domalski, T. Fevig, B. Salisbury, R. Sher, J. Med. Chem. 1996, 39,
1
704 ± 1719.
Me
[
[
8] Du Pont de Nemours and Co., FR 2283681 1976; DE 2539907 1976.
9] W. Nerinckx, M. Vandewalle, Tetrahedron: Asymmetry 1990, 1, 265.
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11] A. P. Degnan, A. I. Meyers, J. Org. Chem. 2000, 65, 3503, and
references therein.
Me
N
Me
HO
Me
H
1
H
[
[
37
N
N
N
A
29
Cl
O
O
O
B
2
6
Cl
30
O
[
12] C.-H. Lin, S. R. Haadsman-Svensson, A. Lahti, R. B. McCall, M. F.
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13] The compatibility of ketone enolates with palladium has also been
demonstrated in the palladium-catalyzed arylation of ketone enolates.
This method also provides an alternative catalytic asymmetric route to
quaternary centers bearing an aryl group, see T. Hamada, A. Chieffi, J.
Arhman, S. L. Buchwald, J. Am. Chem. Soc. 2002, 124, 1261; J. M. Fox,
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1
0
E
24
G
F
C
18
NH
H
O
16
N
H
D
2
: revised structure of diazonamide A
[
decade later, Harran and his group synthesized the proposed
structure 1 only to prove that it was in error, and advanced
structure 2 for diazonamide A instead.[ In the intervening
2]
time, numerous efforts directed at the total synthesis of 1 had
1
360; M. Kawatsura, J. F. Hartwig, J. Am. Chem. Soc. 1999, 121, 1473;
been reported;[
3±13]
no research activities related to the newly
proposed structure 2 have yet been disclosed. The appeal of
diazonamide A (2) stems both from its biological activity
cytotoxicity against several tumor cell lines with IC values
< 15 ngmL ) and its highly strained and unprecedented
J. Ahman, J. P. Wolfe, M. V. Troutman, M. Palucki, S. L. Buchwald, J.
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[
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(
50
ꢀ
1
1
987, 65, 21; T. Volpe, G. Revial, M. Pfau, J. d©Angelo, Tetrahedron
[
*] Prof. Dr. K. C. Nicolaou, Dr. M. Bella, Dr. D. Y.-K. Chen,
Dr. X. Huang, Dr. T. Ling, S. A. Snyder
Department of Chemistry and The Skaggs Institute for Chemical
Biology
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[
15] C. Chassaing, A. Haudrechy, Y. Langlois, Tetrahedron Lett. 2000, 41,
7
2
85; A. Haudrechy, C. Chassaing, C. Riche, Y. Langlois, Tetrahedron
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The Scripps Research Institute
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5
2
1
0550 North Torrey Pines Road, La Jolla, CA 92037 (USA)
Fax : (þ 1)858-784-2469
E-mail: kcn@scripps.edu
and
3, 113; see also D. L. Bai, X. C. Tang, X. C. He, Curr. Med. Chem.
000, 7, 355. For analogues, see P. Camps, E. GÛmez, D. MuÊoz-
Department of Chemistry and Biochemistry
University of California, San Diego
Torrero, M. ArnÛ, Tetrahedron: Asymmetry 2001, 12, 2909.
9
500 Gilman Drive, La Jolla, CA 92093 (USA)
[
**] We thank Dr. D. H. Huang and Dr. G. Siuzdak for NMR spectroscopic
and mass spectrometric assistance, respectively. We also wish to
acknowledge Mr. William R. Webb for his expertise in obtaining low-
resolution mass spectral data. We thank Dr. Paraskevi Giannakakou
and Aurora O©Brate of the Winship Cancer Institute, Emory
University School of Medicine, for the biological assays. Financial
support for this work was provided by The Skaggs Institute for
Chemical Biology, American BioScience, the National Institutes of
Health (USA), predoctoral fellowships from the National Science
Foundation and Pfizer (S.A.S.), and postdoctoral fellowships from The
Skaggs Institute for Research (M.B., X.H., and T.L.).
Angew. Chem. Int. Ed. 2002, 41, No. 18
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