C O M M U N I C A T I O N S
reductive 1,2-elimination for the stereoselective construction of the
C4,13-Z-olefin. Further studies on the total synthesis of chro-
mophore 2 and its various synthetic analogues from 1 are currently
underway in our laboratory.
Acknowledgment. This work was supported financially by
SORST, Japan Science and Technology Agency (JST). A fellowship
to K.K. from the Japan Society for the Promotion of Science (JSPS)
is gratefully acknowledged.
Note Added after ASAP Publication. After this paper was
published ASAP October 23, 2007, the structures of several
compounds were modified in Figure 1 and Scheme 1. The
corrected version was published ASAP October 25, 2007.
Supporting Information Available: General methods and spec-
troscopic and analytical data for selected compounds (PDF). This
Figure 2. NOE and ROE data of the synthetic intermediates (24, 33,
and 34).
References
(1) (a) Zein, N.; Solomon, W.; Colson, K. L.; Schroeder, D. R. Biochemistry
1995, 34, 11591. (b) Schroeder, D. R.; Colson, K. L.; Klohr, S. E.; Zein,
N.; Langley, D. R.; Lee, M. S.; Matson, J. A.; Doyle, T. W. J. Am. Chem.
Soc. 1994, 116, 9351. (c) Hanada, M.; Ohkuma, H.; Yonemoto, T.; Tomita,
K.; Ohbayashi, M.; Kamei, H.; Miyaki, T.; Konishi, M.; Kawaguchi, H.;
Forenza, S. J. Antibiot. 1991, 44, 403.
Scheme 2. Mechanistic Rationale for Formation of 33 and 34
from 32
(2) For a review on chromoprotein antibiotics and other enediyne natural
products, see: Xi, Z.; Goldberg, I. H. In ComprehensiVe Natural Products
Chemistry; Barton, D. H. R., Nakanishi, K., Eds.; Elsevier: Amsterdam,
1999; Vol 7, p 553.
(3) For synthetic studies of the maduropeptin chromophore from this
laboratory, see: (a) Kato, N.; Shimamura, S.; Kikai, Y.; Hirama, M. Synlett
2004, 2107. (b) Kato, N.; Shimamura, S.; Khan, S.; Takeda, F.; Kikai,
Y.; Hirama, M. Tetrahedron 2004, 60, 3161. (c) Khan, S.; Kato, N.;
Hirama, M. Synlett 2000, 1494.
(4) For synthetic studies of the maduropeptin chromophore from other
laboratories, see: (a) Dai, W.-M.; Fong, K. C.; Lau, C. W.; Zhou, L.;
Hamaguchi, W.; Nishimoto, S. J. Org. Chem. 1999, 64, 682. (b) Roger,
C.; Grierson, D. S. Tetrahedron Lett. 1998, 39, 27. (c) Suffert, J.;
Toussaint, D. Tetrahedron Lett. 1997, 38, 5507. (d) Nicolaou, K. C.; Koide,
K.; Xu, J.; Izraelewicz, M. H. Tetrahedron Lett. 1997, 38, 3671. (e)
Nicolaou, K. C.; Koide, K. Tetrahedron Lett. 1997, 38, 3667. (f) Magnus,
P.; Carter, R.; Davies, M.; Elliott, J.; Pitterna, T. Tetrahedron 1996, 52,
6283.
(5) Total synthesis of the proposed structure of kedarcidin, a closely related
enediyne chromophore, was reported. Ren, F.; Hogan, P. C.; Anderson,
A. J.; Myers, A. G. J. Am. Chem. Soc. 2007, 129, 5381.
(6) Inoue, M.; Ohashi, I.; Kawaguchi, T.; Hirama, M. Submitted for
publication.
(7) Ruck, R. T.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 2882.
(8) Kawata, S.; Hirama, M. Tetrahedron Lett. 1998, 39, 8707.
(9) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
(10) Sonogashira, K. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: London, 1990; Vol 3, p 521.
(11) Masamune, S.; Ellingboe, J. W.; Choy, W. J. Am. Chem. Soc. 1982, 104,
5526.
(12) (a) Inoue, M.; Kikuchi, T.; Hirama, M. Tetrahedron Lett. 2004, 45, 6439.
(b) Iida, K.; Hirama, M. J. Am. Chem. Soc. 1994, 116, 10310.
(13) A reagent mixture of LiN(TMS)2 and CeCl3 proved to be less effective
for cyclization of 22 (approximately 30% yield of 23).
(14) Lal, B.; Pramanik, B. N.; Manhas, M. S.; Bose, A. K. Tetrahedron Lett.
1977, 18, 1977.
(15) For related reactions, see: (a) Kurosawa, W.; Kan, T.; Fukuyama, T. J.
Am. Chem. Soc. 2003, 125, 8112. (b) Achatz, O.; Grandl, A.; Wanner, K.
T. Eur. J. Org. Chem. 1999, 1967.
(16) The importance of the macrolactam structure for the Z-selectivity was
suggested by separate experiments. For instance, when a similar substrate
without the 15-membered macrocyclic structure was treated with SmI2,
sole formation of the C4,13-E-olefin was observed. See also ref 3a.
(17) 33:34 ) 2.5:1 (C6D6), 2.1:1 (CDCl3), 1:1.6 (CD3OD), 1:4.1 (DMSO-d6).
(18) The facile atropisomerism of kedarcidin synthetic intermediates has been
observed: Myers, A. G.; Hurd, A. R.; Hogan, P. C. J. Am. Chem. Soc.
2002, 124, 4583. See also ref 5.
It is noteworthy that the ratio of atropisomers 33 and 34 highly
depends on polarity of the solvent,17 and that the chromatographi-
cally separated isomers equilibrated at room temperature to provide
the same mixture of isomers after several hours.18 Most intriguing
is the fact that the acid-promoted global deprotection of the mixture
of 33 and 34 gave rise to aglycon 1 as the sole atropisomer that
corresponds to the natural chromophore 2. The above results
indicate that the rotational barrier of the 2,6-substituted benzene
was unexpectedly low in comparison to the closely related C-1027
chromophore,6,19 and that the energy difference of the deprotected
atropisomers was larger than that of their protected counterparts.
In summary, the total synthesis of the aglycon of the maduropep-
tin chromophore was accomplished for the first time. The key
features of this synthesis are (1) the efficient convergent union of
the three fragments (4, 5, and 6), (2) the cerium amide promoted
nine-membered diyne ring formation, (3) the one-pot macrolactam
formation from the azide-PFP ester, and (4) the SmI2-mediated
(19) Inoue, M.; Sasaki, T.; Hatano, S.; Hirama, M. Angew. Chem., Int. Ed.
2004, 6, 3833.
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