Journal of the American Chemical Society
Article
(4) Ueoka, R.; Ise, Y.; Ohtsuka, S.; Okada, S.; Yamori, T.; Matsunaga,
S. J. Am. Chem. Soc. 2010, 132, 17692.
CONCLUSIONS
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In summary, the total syntheses of the two possible C4-isomers of
1a and 1b were achieved. The key reactions in the present synthesis
include application of the Cu-mediated cross-coupling reactions for
E/Z-selective syntheses of the three dehydroisoleucine derivatives
37, 39, and 41 as well as convergent synthesis of tetrapeptides 6
with the dehydrovaline residue and isomerization-free condensa-
tions of 4, 3, and 5 upon elongation to the targeted compounds.
The syntheses of stereochemically pure 1a and 1b enabled us to
determine the complete stereochemical structure of natural 1 to
be 1a with the C4S-stereochemisty. Our versatile strategy should
be useful for synthesizing various analogues to obtain insights into
the structural and biological roles of dehydro amino acids. Future
studies will include more detailed investigations on the structure−
activity relationships and elucidation of the molecular mode of
action of yaku’amides.
(5) Examples of the natural products that contain dehydrovaline
residue or E-dehydroisoleucine residue. Antrimycin: (a) Shimada, N.;
Morimoto, K.; Naganawa, H.; Takita, T.; Hamada, M.; Maeda, K.;
Takeuchi, T.; Umezawa, H. J. Antibiot. 1981, 34, 1613. Cittariomycin:
(b) Shiroza, T.; Ebisawa, N.; Furihata, K.; Endo, T.; Seto, H.; Otake,
N. Agric. Biol. Chem. 1982, 46, 865. Phomopsins A and B
(c) Culvenor, C. C. J.; Cockrum, P. A.; Edgar, J. A.; Frahn, J. L.;
Gorst-Allman, C. P.; Jones, A. J.; Marasas, W. F. O.; Murray, K. E.;
Smith, L. W.; Steyn, P. S.; Vleggaar, R.; Wessels, P. L. J. Chem. Soc.,
Chem. Commun. 1983, 1259. FR225659 and FR225656: (d) Zenkoh,
T.; Ohtsu, Y.; Yoshimura, S.; Shigematsu, N.; Takase, S.; Hino, M. J.
Antibiot. 2003, 56, 694.
(6) (a) Rajashankar, K. R.; Ramakumar, S.; Jain, R. M.; Chauhan, V.
S. J. Am. Chem. Soc. 1995, 117, 11773. (b) Thormann, M.; Hofmann,
H.-J. J. Mol. Struct (Theochem) 1998, 431, 79. (c) Siodłak, D.; Grondys,
J.; Lis, T.; Bujak, M.; Broda, M. A.; Rzeszotarska, B. J. Pept. Sci. 2010,
16, 496.
ASSOCIATED CONTENT
* Supporting Information
Characterization data for all new compounds and experimental
procedures. This material is available free of charge via the
(7) (a) Rich, D. H.; Bhatnager, P. K. J. Am. Chem. Soc. 1978, 100,
■
2212. (b) Ward, D. E.; Vaz
1999, 64, 1657.
́
quez, A.; Pedras, M. S. C. J. Org. Chem.
S
(8) (a) Yamori, T. Cancer Chemother. Pharmacol. 2003, 52, S74.
(b) Yaguchi, S.; Fukui, Y.; Koshimizu, I.; Yoshimi, H.; Matsuno, T.;
Gouda, H.; Hirono, S.; Yamazaki, K.; Yamori, T. J. Natl. Cancer Inst.
2006, 98, 545. (c) Yamori, T.; Matsunaga, A.; Sato, S.; Yamazaki, K.;
Komi, A.; Ishizu, K.; Mita, I.; Edatsugi, H.; Matsuba, Y.; Takezawa, K.;
Nakanishi, O.; Kohno, H.; Nakajima, Y.; Komatsu, H.; Andoh, T.;
Tsuruo, T. Cancer Res. 1999, 59, 4042.
AUTHOR INFORMATION
Corresponding Author
■
(9) We recently reported the total synthesis and biological evaluation
of polytheonamide B, a structurally related polypeptide, and its
synthetic analogues. Structure of polytheonamide: (a) Hamada, T.;
Matsunaga, S.; Yano, G.; Fusetani, N. J. Am. Chem. Soc. 2005, 127, 110.
The total synthesis of polytheonamide B: (b) Inoue, M.; Shinohara,
N.; Tanabe, S.; Takahashi, T.; Okura, K.; Itoh, H.; Mizoguchi, Y.; Iida,
M.; Lee, N.; Matsuoka, S. Nat. Chem. 2010, 2, 280. Structure−activity
relationship studies: (c) Matsuoka, S.; Shinohara, N.; Takahashi, T.;
Iida, M.; Inoue, M. Angew. Chem., Int. Ed. 2011, 50, 4879.
(d) Shinohara, N.; Itoh, H.; Matsuoka, S.; Inoue, M. ChemMedChem
2012, 7, 1770. (e) Itoh, H.; Matsuoka, S.; Kreir, M.; Inoue, M. J. Am.
Chem. Soc. 2012, 134, 14011.
(10) Although the biosynthesis of yaku’amides is not elucidated, Piel
and co-workers suggested a ribosomal origin of yaku’amides. They
proved that polytheonamide B is a posttranslationally modified
ribosomal peptide. Freeman, M. F.; Gurgui, C.; Helf, M. J.;
Morinaka, B. I.; Uria, A. R.; Oldham, N. J.; Sahl, H.-G.; Matsunaga,
S.; Piel, J. Science 2012, 338, 387.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was financially supported by the Funding
Program for Next Generation World-Leading Researchers
(JSPS) to M.I. and a Grant-in-Aid for Young Scientists (B)
(JSPS) to T.K. We thank Prof. Shigeki Matsunaga and Ms. Emi
Takanashi (The University of Tokyo) for bioactivity evaluation.
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dx.doi.org/10.1021/ja401457h | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX