Organic Letters
Letter
(5) (a) Seebach, D.; Overhand, M.; Kuhnle, F. N. M.; Martinoni, B.;
Oberer, L.; Hommel, U.; Widmer, H. Helv. Chim. Acta 1996, 79, 913.
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stereochemically feasible. The observed switch from the C11/C9
mixed helix to the C11 continuous helix on going from the
tripeptides to the tetrapeptides may be attributed to the energy
penalty that needs to be paid for the Aib residues to adopt the PII
conformation,18 which is a requirement for C11/C9 helix
formation. In principle, at the tetrapeptide level two intra-
molecular hydrogen bonds will be formed in both types of
helices. The balance between these two helix types is then tilted
by the conformational preferences of the Aib residue, which are
determined by intraresidue nonbonded interactions. Hybrid
(αβ)n sequences containing chiral α-residues and achiral β
residues may provide an attractive model system for studying
transitions in peptide helices between structures with unidirec-
tional hydrogen bonds and mixed helices. Designed, model (ββ)n
peptides containing alternating chiral and achiral residues may be
useful in experimentally probing the distribution of C14 helices (1
→ 3, reverse hydrogen bond directionality), C12 helices (4 → 1,
conventional hydrogen bond directionality), and C12/C10
structures (mixed directionality). Notably the analogous C10/
C8 structures in all α-polypeptides may be difficult to realize
because of the requirement of a cis peptide bond to facilitate the
C8 hydrogen bond.23
(6) (a) Seebach, D.; Gademann, K.; Schreiber, J. V.; Matthews, J. L.;
Hintermann, T.; Jaun, B.; Oberer, L.; Hommel, U.; Widmer, H. Helv.
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H.-J. Biopolymers 1999, 50, 167. (b) Baldauf, C.; R. Gunther, R.;
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Hofmann, H.-J. Angew. Chem., Int. Ed. 2004, 43, 1594. (c) Baldauf, C.; R.
Gunther, R.; Hofmann, H.-J. Biopolymers 2005, 80, 675. (d) Schramm,
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P.; Sharma, G. V. M; Hofmann, H.-J. Biopolymers 2010, 94, 279.
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(b) Wu, Y.-D.; Wang, D.-P. J. Am. Chem. Soc. 1999, 121, 9352. (c) Wu,
Y.-D.; Han, W.; Wang, D.-P.; Gao, Y.; Zhao, Y.-L. Acc. Chem. Res. 2008,
41, 1418.
(9) Lin, Z.; Timmerscheidt, T. A.; van Gunsteren, W. F. J. Chem. Phys.
2012, 137, 064108.
The present study emphasizes the utility of the constrained β-
residue β2,2Ac6c in designing specific types of hydrogen-bonded
helical structures in (αβ)n hybrid sequences, by varying the
nature of the α residue.
(10) Gruner, S. A. W.; Truffault, V.; Voll, G.; Locardi, E.; Stockle, M.;
̈
Kessler, H. Chem.Eur. J. 2002, 8, 4365.
(11) (a) Sharma, G. V. M; Reddy, K. R.; Krishna, P. R.; Ravi Sankar, A.;
Narsimulu, K.; Kiran Kumar, S.; Jayaprakash, P.; Jagannadh, B.; Kunwar,
A. C. J. Am. Chem. Soc. 2003, 125, 13670. (b) Sharma, G. V. M; Reddy,
K. R.; Krishna, P. R.; Ravi Sankar, A.; Jayaprakash, P.; Jagannadh, B.;
Kunwar, A. C. Angew. Chem., Int. Ed. 2004, 43, 3961. (c) Sharma, G. V.
M; Manohar, V.; Dutta, S. K.; Subash, V.; Kunwar, A. C. J. Org. Chem.
2008, 73, 3689.
ASSOCIATED CONTENT
* Supporting Information
■
S
Details of synthetic procedure, X-ray diffraction data, structure
solution, and refinement procedures and supplementary tables.
This material is available free of charge via the Internet at http://
988391 (1), 988392 (2), 988393 (3), and 988394 (4), which
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge
(12) Sharma, G. V. M; Nagendar, P.; Jayaprakash, P.; Krishna, P. R.;
Ramakrishna, K. V. S.; Kunwar, A. C. Angew. Chem., Int. Ed. 2005, 44,
5878.
(13) Baldauf, C.; Gunther, R.; Hofmann, H.-J. Biopolymers 2006, 84,
̈
408.
(14) Man
Vass, E.; Fulop, F. Angew. Chem., Int. Ed. 2009, 48, 2171.
́
́ ́
dity, I. M.; Weber, E.; Martinek, T. A.; Olajos, G.; Toth, G. K.;
̈
̈
(15) (a) Tanaka, M.; Oba, M.; Ichiki, T.; Suemune, H. Chem. Pharm.
Bull. 2001, 49, 1178. (b) Saavedra, C.; Hernan
E. J. Org. Chem. 2009, 74, 4655. (c) Andre, C.; Legrand, B.; Deng, C.;
́
́
dez, R.; Boto, A.; Alvarez,
́
AUTHOR INFORMATION
Corresponding Author
■
Didierjean, C.; Pickaert, G.; Martinez, J.; Averlant-Petit, M. C.; Amblard,
M.; Calmes, M. Org. Lett. 2012, 14, 960. (d) Basuroy, K.; Karuppiah, V.;
Shamala, N.; Balaram, P. Helv. Chim. Acta 2012, 95, 2589.
(16) (a) Vasudev, P. G.; Chatterjee, S.; Ananda, K.; Shamala, N.;
Balaram, P. Angew. Chem., Int. Ed. 2008, 47, 6430. (b) Guo, L.; Zhang,
W.; Guzei, I. A.; Spencer, L. C.; Gellman, S. H. Org. Lett. 2012, 14, 2582.
(17) Lee, M.; Shim, J.; Kang, P.; Guzei, I. A.; Choi, S. H. Angew. Chem.,
Int. Ed. 2013, 52, 12564.
(18) Aravinda, S.; Shamala, N.; Balaram, P. Chem. Biodiversity 2008, 5,
1238.
(19) (a) Choi, S. H.; Guzei, I. A.; Gellman, S. H. J. Am. Chem. Soc. 2007,
129, 13780. (b) Choi, S. H.; Guzei, I. A.; Spencer, L. C.; Gellman, S. H. J.
Am. Chem. Soc. 2008, 130, 6544.
(20) Srinivasulu, G.; Kiran Kumar, S.; Sharma, G. V. M; Kunwar, A. C.
J. Org. Chem. 2006, 71, 8395.
(21) Hayen, A.; Schmitt, M. A.; Ngassa, F. N.; Thomasson, K. A.;
Gellman, S. H. Angew. Chem., Int. Ed. 2004, 43, 505.
(22) Basuroy, K.; Dinesh, B.; Shamala, N.; Balaram, P. Angew. Chem.,
Int. Ed. 2012, 51, 8736.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported under the DBT-IISc partnership
program. V.K. was supported by a UGC D. S. Kothari
postdoctoral fellowship. We thank Dr. S. Raghothama for the
13C NMR spectra.
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