dimethylformamide). Then DCC (0.56 g, 2.7 mmol; 1,3-dicyclo-
hexylcarbodiimide) was added to the cooled mixture, which
was stirred for 2 days at room temperature. The residue was
then taken into ethyl acetate (50 ml) and the DCU (N,NЈ-
dicyclohexylurea) was filtered off. The organic layer was washed
with 2 M HCl (3 × 50 ml), 1 M sodium carbonate (3 × 50 ml)
and brine (2 × 50 ml), dried over anhydrous sodium sulfate and
evaporated in vacuo to yield a solid material. The crude peptide
was purified by silica-gel column chromatography using
CH3OH–CHCl3 as eluent (yield 65%). The pure peptide was
crystallized from CH3OH–H2O. Rf = 0.47 (CHCl3–CH3OH =
26
578
9.5 ml : 0.5 ml) in TLC. [α] = Ϫ44.96Њ (c = 0.10 g per 100 ml;
CH3OH). IR (KBr): 3327 (N–H), 1722 (ester CO), 1675 (amide
CO) cmϪ1 1H NMR (300 MHz, CDCl3): δ 1.43 (3H, d,
.
Fig. 1 Crystal structure of the model dipeptide Boc--Ala-m-ABA-
Ala-Cβ-H), 1.46 (9H, s, -C(CH3)3), 3.90 (3H, s, -OCH3), 4.37
(1H, m, Ala-Cα-H), 5.19 (1H, d, Ala-NH), 7.35, 7.74, 7.80, 8.08
(4 Ar-H), 8.82 (1H, s, m-ABA-NH).
OMe.
Conclusion
Crystal data†
The dipeptide shows remarkable properties of self-assembly
to form a distorted, parallel β-sheet structure through inter-
molecular hydrogen-bonding and π–π interactions. The present
model may increase our understanding of β-sheet polypeptides.
Importantly, the system may provide insights about the struc-
ture and function of peptides involved in the pathogenesis and
therapeutics of conformational diseases.
C16H22N2O5, M = 322.36, monoclinic, a = 5.092(2), b =
28.928(9), c = 5.702(2) Å, β = 90.02(2)Њ, V = 839.97(5) Å3,
T = 294 K, space group P21, Z = 2, µ = 0.10 mmϪ1, 3553
reflections measured, 1818 unique reflections, Rint = 0.024.
The experimental data were collected at room temperature
using a Nonius-Kappa CCD diffractometer with Mo-Kα
radiation (λ = 0.71069 Å) and the ꢀ-ω scan technique [Ϫ6 р
h р 6, Ϫ35 р k р 37, Ϫ6 р l р 7]. The structure was solved
by direct methods (SHELXS-97).12 The non-hydrogen atoms
were refined anisotropically using full-matrix least squares on
F 2 (SHELXL-97).12 The final R-value was 0.0335, wR2 =
0.0884, S = 1.011 using 263 parameters and 1 restraint with a
Flack parameter of 0.8(11). The weighting scheme, w =
Experimental
Synthesis
Methyl m-aminobenzoate. A mixture of absolute methanol
(20 ml) and m-aminobenzoic acid (10 mmol, 1.37 g) was cooled
in an ice–salt bath for 30 minutes. Then thionyl chloride (about
15 ml) was added dropwise with stirring. The reaction mixture
was slowly allowed to come to room temperature. After 15 h of
stirring of the clear reaction mixture, the excesses of methanol
and thionyl chloride were removed and the residue was treated
with ether. The solid methyl ester hydrochloride was then
filtered and washed with ether. This hydrochloride salt (1.03 g)
was dissolved in water (25 ml) and neutralized with Na2CO3.
Then methyl m-aminobenzoate was extracted with ethyl acetate
(2 × 25 ml) and isolated by removal of solvent. This liquid ester
(3 ml) was used for the synthesis of the dipeptide without
2
2
1/[σ2(Fo ) ϩ (0.0531 P)2 ϩ 0.06 P] where P = max (Fo , 0) ϩ
2Fc2)/3 gave satisfactory analysis of the variance. The absolute
configuration of the system could not be determined by X-ray
methods. Data collection: COLLECT;13 cell refinement:
DENZO-SMN;14 data reduction: DENZO-SMN; molecular
graphics: PLATON.15
Acknowledgements
PAM acknowledges the award of a Senior Research Fellowship
from the CSIR (New Delhi). SKK and AP are grateful to the
UGC, New Delhi and the University of Calcutta for providing
financial support.
further purification. IR (KBr): 1711 (CO) cmϪ1 1H NMR
.
(300 MHz, CDCl3): δ 3.73 (2H, s, -NH2), 3.78 (3H, s, -OCH3),
6.79, 7.14, 7.32, 7.37 (4 Ar-H).
Boc-L-Ala-m-ABA-OMe. The isolated methyl m-amino-
benzoate (3 ml) was added to an ice-cooled solution of
Boc--Ala-OH (0.51 g, 2.7 mmol) in 15 ml of DMF (N,N-
p2/b2/b203164g/ for crystallographic files in .cif or other electronic
format.
Fig. 2 A stereoview of the hydrogen-bonding pattern in the system.
J. Chem. Soc., Perkin Trans. 2, 2002, 1602–1604
1603