C2-SYMMETRIC CYCLOTETRAPEPTIDE
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Linear compound 7 has three amide protons: one is HꢀꢀN of
anthranilic moiety (Ha), and two are HꢀꢀN of leucyl moieties
(Hb). Both amide protons (Ha and Hb) of 7 downshifted in
DMSO-d6, which is a stronger hydrogen acceptor than
CDCl3. Although protons (Hb) of 1 downshifted similarly in
DMSO-d6, protons (Ha) of 1 did not downshift. This sug-
gests that the concave hydrogen-bonding network of 1 pre-
vents DMSO from binding to Ha.
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To obtain additional information about the characteristics
of the hydrogen-bonding network, we carried out an HꢀꢀD
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1
exchange experiment of 1 in H NMR. If this proton is cap-
tured by the strong hydrogen bond, a slow HꢀꢀD exchange
will be observed in deuterium MeOH. However, the HꢀꢀD
exchange of 1 occurred on the protons Ha and proton Hb
within 2 min. Furthermore, titration of MeOH-d4 into a
CDCl3 solution of 1 showed that the HꢀꢀD exchange of both
Ha and Hb proceeded at the same time. Judging from these
results, the hydrogen bond in the concave network of 1 was
weaker than it looked, even though the hydrogen was cap-
tured by both three-centered hydrogen bonds and bifurcated
hydrogen bonds.
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thranilic acid and leucine. The C2-bowl structure was con-
firmed by single-crystal X-ray analysis and kept in a solution
state. The cyclic compound had a concave hydrogen-bonding
network composed of three-centered hydrogen bonds and bi-
furcated hydrogen bonds. However, the hydrogen atoms
were weakly captured, and a rapid HꢀꢀD exchange with d4-
methanol was observed. This tetrapeptide and the related
analog would be added to the group of C2-bowl-shaped build-
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Chirality DOI 10.1002/chir