F. Li et al. / Tetrahedron Letters 50 (2009) 2367–2369
2369
ent functionalities with an aim to investigate their interactions
with different guest molecules.
Acknowledgments
This work was financially supported by the ‘Hundred talents’
program of the Chinese Academy of Sciences and the National Nat-
ural Science Foundation of China (2072127). We also thank Profes-
sor Q.-Y. Zheng at ICCAS for his helpful suggestion on the crystal
structure analysis.
Supplementary data
Supplementary data associated (synthetic procedures of com-
1
13
pound 1–7 and relevant H and C NMR spectra, variable temper-
1
ature and concentration H NMR spectra of 1a and 1b, and
Figure 4. Crystal structures of macrocycle 1a (a) top view, (b) side view, (c)
stacking view. (side chains and hydrogen atoms irrelevant to hydrogen bonds in (b)
and (c) were all removed for clarity).
References and notes
1. For reviews, see: (a) Zhang, W.; Moore, J. S. Angew. Chem., Int. Ed. 2006, 45,
4
7
416–4439; (b) Li, Z.-T.; Hou, J.-L.; Li, C.; Yi, H.-P. Chem. Asian. J. 2006, 1, 766–
88; (c) Li, Z.-T.; Hou, J.-L.; Li, C. Acc. Chem. Res. 2008, 41, 1343–1353; (d) Gong,
of 0.26, 0.21, 0.16, and 0.09 ppm, respectively, while for 1b
(Fig. 3b), each signal changed in the same trend by upfield shifts
B. Acc. Chem. Res. 2008, 41, 1376–1386.
of 0.33, 0.25, 0.19, and 0.10 ppm, respectively. The chemical shift
changes were probably caused by the intermolecular aromatic
stacking interactions. It is noteworthy that the protons of macrocy-
clic peptide 1b shifted more than their counterparts in 1a, which
might be attributed to the stronger aromatic stacking interactions
aided by the capabilities of the longer side chains of 1b to inter-
twine, intermolecularly.
2. For examples, see: (a) Pan, G.-B.; Cheng, X.-H.; Höger, S.; Freyland, W. J. Am.
Chem. Soc. 2006, 128, 4218–4219; (b) Shu, L.; Mayor, M. Chem. Commun. 2006,
4134–4136; (c) Naddo, T.; Che, Y.; Zhang, W.; Balakrishnan, K.; Yang, X.; Yen,
M.; Zhao, J.; Moore, J. S.; Zang, L. J. Am. Chem. Soc. 2007, 129, 6978–6979.
3. Sanford, A. R.; Yuan, L.; Feng, W.; Yamato, K.; Flowers, R. A.; Gong, B. Chem.
Commun. 2005, 4720–4722.
4
5
.
.
Zhu, Y.-Y.; Li, C.; Li, G.-Y.; Jiang, X.-K.; Li, Z.-T. J. Org. Chem. 2008, 73, 1745–1751.
Helsel, A. J.; Brown, A. L.; Yamato, K.; Feng, W.; Yuan, L.; Clements, A. J.;
Harding, S. V.; Szabo, G.; Shao, Z.; Gong, B. J. Am. Chem. Soc. 2008, 130, 15784–
15785.
The crystals suitable for X-ray diffraction analysis were grown
by slow evaporation of solvent from chloroform–methanol–tolu-
6.
(a) Masu, H.; Okamoto, T.; Kato, T.; Katagiri, K.; Tominaga, M.; Goda, H.;
Takayanagi, H.; Azumaya, I. Tetrahedron Lett. 2006, 47, 803–807; (b) Kang, S.
W.; Gothard, C. M.; Maitra, S.; Atiatul, W.; Nowick, J. S. J. Am. Chem. Soc. 2007,
1
3
ene solution. The solid state structure is presented in Figure 4.
Macrocycle 1a consisted of an almost flat disc in the crystal struc-
ture. As expected, the four amide protons were all involved in
intramolecular three-center hydrogen bonding. The disordered
methoxyl groups pointed to either surfaces of the disc while all
the amide oxygen atoms pointed outwards from the circumfer-
ence. The four quinoline rings were not all coplanar in general.
Two quinoline rings in each independent crystallographic unit
were held in the same plane via the hydrogen bonding [N4ÁÁÁN1
1
29, 1486–1487; (c) Campbell, P.; Plante, J.; Carruthesrs, C.; Hardie, M. J.; Prior,
T. J.; Wilson, A. J. Chem. Commun. 2007, 2240–2242.
Bong, D. T.; Clark, T. D.; Granja, J. R.; Ghadiri, M. R. Angew. Chem., Int. Ed. 2001,
40, 988–1011.
7
8
.
.
(a) Jiang, H.; Léger, J. M.; Guionneau, P.; Huc, I. Org. Lett. 2004, 6, 2985–2988;
(
b) Shirude, P. S.; Gillies, E. R.; Ladame, S.; Godde, F.; Shin-ya, K.; Huc, I.;
Balasubramanian, S. J. Am. Chem. Soc. 2007, 129, 11890–11891.
Gan, Q.; Bao, C.; Kauffmann, B.; Gréard, A.; Xiang, J.; Liu, S.; Huc, I.; Jiang, H.
Angew. Chem., Int. Ed. 2008, 47, 1715–1718.
9.
1
0. Heindel, N. D.; Bechara, I. S.; Lemke, T. F.; Fish, V. B. J. Org. Chem. 1967, 32,
155–4157.
4
2
.592(2) Å, N4ÁÁÁO6 2.647(3) Å], and associated with the other
1
1. Regarding dichlorotriphenylphopshorane as an amide coupling reagent, its
possible mechanism see: Azumaya, I.; Okamoto, T.; Imabeppu, F.; Takayanagi,
H. Tetrahedron 2003, 59, 2325–2331.
pair, which are tilted out of plane, by similar intramolecular
interaction [N2ÁÁÁN3 2.572(9) Å, N2ÁÁÁO3 2.651(6) Å, dihedral angle
12. General synthetic procedure for the macrocycles: To a stirred solution of
1
6.2°] to create the dish-like conformation. Unexpectedly, along a
compound 2a or 2b (1.0 mmol) in dry THF (30 mL), under an atmosphere of
argon was added dichlorotriphenylphosphorane (1.33 g, 4.0 mmol) and the
solution was heated to reflux for 8–14 h. The solvent was evaporated under
reduced pressure and the residue was further purified by silica gel column
chromatography to yield the macrocycles 1a or 1b. 1a: white powder, mp
axis, two macrocyclic dishes initially assembled together to form
a dimeric unit by stable face-to-face aromatic stacking inter-
actions with slight slippage, centroid distances of 3.722(2) and
.654(2) Å. Furthermore, partial face-to-face interactions
centroid distances of 3.584(2) Å) of the dimers prevented the col-
p–p
1
4
1
3
p
–p
>300 °C. H NMR (400 MHz, 4 mM, CDCl ): 11.63 (s, 4H), 8.10 (d, J = 8.9 Hz, 4H),
3
7
2
1
.64 (d, J = 8.9 Hz, 4H), 7.55 (s, 4H), 4.36 (s, 12H), 4.30 (d, J = 6.2 Hz, 8H), 2.52–
.46 (m, 4H), 1.38 (d, J = 6.6 Hz, 24H). 13C NMR (100 MHz, 20 mM, CDCl
):
63.9, 161.2, 150.0, 141.5, 140.0, 131.6, 118.8, 117.7, 117.3, 97.1, 75.4, 63.1,
(
3
umn-pattern stacking observed in other macrocycles, but in
agreement with the reported macrocycles containing methoxyl
+
28.7, 19+ .6. MALDI-TOF MS: m/z calcd for [M+H] 1089.5, found 1089.8;
4
1
[
M+Na] 1111.5, found 1111.7. 1b: pale yellow powder, mp = 198–200 °C.
H
groups.
NMR (600 MHz, 10 mM, CDCl ): d 11.69 (s, 4H), 8.18 (d, J = 8.4 Hz, 4H), 7.65 (d,
3
In conclusion, two novel shape-persistent macrocyclic pep-
J = 8.4 Hz 4H), 7.50 (s, 4H), 4.50 (s, 8H), 4.39 (s, 12H), 2.14–2.17 (m, 8H), 1.77–
tides were synthesized directly from
e-aminoquinoline-carbox-
1.80 (m, 8H), 1.58–1.60 (m, 8H), 1.36 (br m, 56H), 0.88–0.91 (t, 12H). 13C NMR
ylic acid in one step with moderate yields. In this process,
hydrogen bonding interactions were rationalized to play an
important role of assisting the oligoamide intermediates to fold
and facilitated cyclization. We believe that our synthetic method
of preparing the cyclic peptides could provide an expedient
route in the development of such macrocycles. Currently, we
are exploring Aqc-based macrocyclic peptides possessing differ-
3
(100 MHz, 10 mM, CDCl ): d 164.0, 161.3, 150.1, 141.9, 140.2, 131.9, 119.0,
1
1
1
17.9, 117.7, 97.1, 69.4, 63.1, 32.1, 31.0, 30.0, 29.9, 29.8, 29.6, 29.5, 26.5, 22.9,
4.3. MALDI-TOF MS: m/z calcd for [M+H] 1537.0, found 1537.8; [M+Na]+
+
559.0, found 1559.8.
13. Crystal data of 1a:
a = 25.347(5), b = 28.709(6),
Dc = 1.203 Mg/m , T = 113 K, crystal size 0.20 Â 0.20 Â 0.20 mm , R = 0.1309,
C H65Cl N O , M = 1208.56, orthorhombic, Fddd,
61 3 8 12
3
c = 36.676(7) Å,
(I)], GOF on F2 = 1.482,
14. Janiak, C. J. Chem. Soc., Dalton Trans. 2000, 3885–3896.
V = 26689(9) Å ,
Z = 16,
3
3
À1
wR
2
= 0.3641 [I>2
r
l = 0.199 mm , CCDC-715184.