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ChemComm
DOI: 10.1039/C5CC08324A
COMMUNICATION
Journal Name
the 1H and 13C NMR spectra of 1a and 1b with the spectroscopic
data recorded for natural scytonemin A clearly showed that the
3
4
T. K. Chakraborty, A. K. Hussain, S. P. Joshi, Chem Lett, 1992, 21
385
Y. Yoon, M. Chun, J. Joo, Y. Kim, C. Oh, K. Lee, Y. Lee, W. Ham, Arch.
Pharmacal Res. 2004, 27, 136.
,
2
(
9R)-isomer (1a) was identical in all aspects, whereas the (9S)-
isomer (1b) showed several significant differences, especially at
C-9 carbon of the Ahda moiety (also see Supplementary
Information). Finally, co-injection of 1a and 1b as well as the
authentic sample of the natural product on chiral HPLC revealed
that the (9R)-isomer (1a) and the natural product were
indistinguishable. Taken together, the excellent correlation of
the H and 13C spectra of the synthetic (9R)-isomer (1a) with
5
6
E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 13, 3769.
T. V. Kumar, G. V. Reddy, K. S. Babu, J. M. Rao, Tetrahedron:
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7
8
M. Yamaguchi, I. Hirao, Tetrahedron Lett. 1983, 24, 391.
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3041.
3,
9
1
W. C. Still, C. Gennari, Tetrahedron Lett. 1983, 24, 4405.
0 Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, K. B.
Sharpless, J. Am. Chem. Soc. 1987, 109, 5765.
1
those of the natural product and the similar optical rotations of 11 Both diols 16 and 17 were converted into the corresponding
acetonides and submitted to structural analysis. Please also see: K.
the natural material and synthetic (9R)-isomer (1a) enabled us
Pihlaja, E. Kleinpeter, Carbon-13 NMR Chemical Shifts in Structural
to assign the stereogenic center at C9 of the Ahda moiety of
and Stereochemical Analysis, 1994, Wiley-VCH, New York, pp. 55.
naturally occurring scytonemin A as (R)-configured.
12 a) M. Zhao, J. Li, E. Mano, Z. Song, D. M. Tschaen, E. J. J. Grabowski,
P. J. Reider J. Org. Chem. 1999, 64, 2564.; b) L. De Luca, G.
Giacomelli, S. Masala, A. Porcheddu, J. Org. Chem. 2003, 68, 4999.
1
3 F. Albericio, M. Cases, J. Alsina, S. A. Triolo, L. A. Carpino, S. A.
Kates, Tetrahedron Lett. 1997, 38, 4853.
Conclusions
1
1
1
4 C. Herdeis, H. P. Hubmann, Tetrahedron Asymmetry 1994,
5 A. Hamajima, M. Isobe, Angew. Chem. Int. Ed. 2009, 48, 2941.
6 Dipeptide was prepared via condensation of Cbz-protected
glycine with the methyl ester of the known -hydroxy leucine: L.
Williams, Z. D. Zhang, F. Shao, P. J. Carroll, M. M. Joullié,
Tetrahedron 1996, 52, 11673.
5, 351.
In summary, the first total synthesis of scytonemin A proceeded
in 28 steps and 0.57% overall yield (longest linear sequence
from the known and easily accessible methyl ester 8). The route
detailed herein is convergent and flexible, thereby allowing for
the synthesis of the C9 epimer that facilitated the stereochemical
5
β
1
7 Tripeptide 7 was prepared in three steps from the known bis-
assignment. Notable features of the synthesis include
a
protected homoserine. R. M. Williams, L. K. Maruyama, J. Org.
Chem. 1987, 52, 4044. For details, please see Supplementary
Information.
8 L. Wang, J. Liu, H. Zhang, Z. Xu, T. Ye, Synlett 2010, 17, 563.
9 M. Valencic, T. van der Does, T.; E. de Vroom, Tetrahedron Lett.
1998, 39, 1625.
regioselective epoxide-opening process, TEMPO-catalyzed
selective oxidation of 1,2-diol to the corresponding hydroxy acid,
DDQ-mediated deprotection of benzyl ether, TiCl -promoted
4
deprotection of both tert-butyl ester and Boc carbamate at a late
stage in the synthesis. These studies reinforce the vital role that
total synthesis continues to play in determining the actual
structures of promising natural products.
1
1
We thank Dr Gregory L. Helms of Washington State University
for providing an authentic sample of scytonemin A. Fong Shu
Fook Tong Foundation and Joyce M. Kuok Foundation; the
National Natural Science Foundation of China (21072007,
21272011, 21133002), Shenzhen Science and Technology
Development Fund (JCYJ20130329175740481,
JCYJ20140419131807793) and Shenzhen Peacock Plan partly
supported this work.
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