Glycyrrhizic acid based self-assembled helical nanostructures as scaffolds for asymmetric Diels-Alder reaction

Article abstract of DOI:10.1016/j.cclet.2019.02.015

Glycyrrhizic acid (GA), as a traditional herbal, can self-assemble into helical nanofiber in the water. The formed helical nanostructures can be employed as scaffolds for asymmetric Diels-Alder reaction. Through co-assembling with a series of achiral copper-ligands, the chirality of GA helical nanostructures can be transferred to catalytic site, and resulted assemblies showed moderated enantioselectivity toward catalysis of Diels-Alder reaction.

Full text of DOI:10.1016/j.cclet.2019.02.015

G Model
CCLET 4817 No. of Pages 3
Chinese Chemical Letters xxx (2019) xxx–xxx
Contents lists available at ScienceDirect
Chinese Chemical Letters
journal homepage: www.elsevier.com/locate/cclet
Communication
Glycyrrhizic acid based self-assembled helical nanostructures as
scaffolds for asymmetric Diels-Alder reaction
a,b
b
b,
b
a,
Yimeng Sun , Yan Meng , Jian Jiang *, Hui Sun , Tiesheng Li *
a
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, China
National Centre for Nanoscience and Technology, Beijing 100190, China
b
A R T I C L E I N F O
A B S T R A C T
Article history:
Glycyrrhizic acid (GA), as a traditional herbal, can self-assemble into helical nanofiber in the water. The
formed helical nanostructures can be employed as scaffolds for asymmetric Diels-Alder reaction.
Through co-assembling with a series of achiral copper-ligands, the chirality of GA helical nanostructures
can be transferred to catalytic site, and resulted assemblies showed moderated enantioselectivity toward
catalysis of Diels-Alder reaction.
Received 28 December 2018
Received in revised form 1 February 2019
Accepted 20 February 2019
Available online xxx
©
2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
Published by Elsevier B.V. All rights reserved.
Keywords:
Glycyrrhizic acid
Helical nanofiber
Co-assembly
Asymmetric catalysis
Diels-Alder reaction
Helical architecture is one of the most interesting structures in
nature. In biological system, helical structure is ubiquitous, for
example double-helix DNA and α-helical protein [1–5], both
dominate diverse physiological active function in the organism.
Inspired by bio-system helix, various artificial helical architectures,
such as helical polymers, self-assembled helical nanostructures
and organic-inorganic hybrid helical nanomaterials, have been
fabricated successfully [6–8]. In recent years, increasing interest
has extended to apply natural and artificial helical structures in the
field of chiral recognition, chiral separation and circularly
polarized luminescence [9–22]. In particular, helical architectures
for asymmetric catalysis have attracted a lot of attentions, for
instance, double helix DNA, helical polymer and self-assembled
helical nanotubes have been utilized as chiral scaffolds for
asymmetric catalysis [23–34]. As a matter of fact, various natural
products have been found to form helical nanostructures via self-
assembly, however, little has been employed for asymmetric
catalysis [35–37]. Therefore, it is highly desirable to explore
enantioselective catalytic performance of natural helical assembly.
Glycyrrhizic acid (GA) is a traditional Chinese medicinal herbal,
which has been applied for the treatment of liver diseases [38].
Recently, it was reported that GA could self-assemble into right
handed helical nanofiber in water [39]. Herein, we tried to utilize
GA based helical nanostructures as scaffolds for asymmetric
catalysis. The catalyst was prepared by self-assembly of the achiral
copper (II)-ligand with GA (named as GA-L, Fig. 1). And we found
that helical nanostructure were well preserved if the molar ratio of
copper (II) species to GA around a proper scope. GA-L assemblies
gave moderated enantioselectivity toward Diels-Alder reaction
and up to 61% ee was obtained.
GA-L was constructed via co-assembly of the copper (II) ions
coordinated ligands (L1-L6) and GA. GA was first heated to dissolve
in water (1 wt%). Upon cooling, copper (II)-ligands in water
solution were injected into GA solution and mixed by shaking,
the resulted mixture solution was further stand at room
temperature for about 12 h.
The morphology of GA-L assembly was investigated by AFM
(Atomic Force Microscope). L6 was selected as a mode ligand, and
we found helical nanofibers were well preserved when the L6
amount is below 5% (molar ratio to GA). In addition, the
homogenous transparent bright yellow hydrogel was formed (
Figs. Fig. 22a and Fig. 22b ). Further increase the amount of L6, the
hydrogel would be destroyed and turned into yellow precipitate, in
which two nanostructures of nanofiber and amorphous nano-
structures were observed (Figs. Fig. 22c and Fig. 22d), indicating
some extra of L6 were not incorporated into helical nanofibers.
UV-vis and CD spectra were monitored in order to investigate
the supramolecular chirality of GA-L6 assembly. GA hydrogel have
no CD signal between 320 nm–450 nm (Fig. 3, dotted line), while a
negative cotton effect at 352 nm was observed for GA-L6 hydrogel,
*
Corresponding authors.
E-mail addresses: jiangj@nanoctr.cn (J. Jiang), lts34@zzu.edu.cn (T. Li).
https://doi.org/10.1016/j.cclet.2019.02.015
001-8417/© 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.
1
Please cite this article in press as: Y. Sun, et al., Glycyrrhizic acid based self-assembled helical nanostructures as scaffolds for asymmetric Diels-
Alder reaction, Chin. Chem. Lett. (2019), https://doi.org/10.1016/j.cclet.2019.02.015

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CCLET 4817 No. of Pages 3
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Y. Sun et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
Fig. 1. Molecular structure of GA and catalyst by co-assembly of GA with copper(II)-
ligand (L1-L6), Diels-Alder reaction was selected as a model reaction.
Fig. 3. UV–vis and CD spectra of GA (dotted line) and GA-L6 (solid line) assemblies,
% of L6 to GA (molar ratio) was used.
5
Table 1
GA-L-assembly for catalysis of the Diels-Alder reaction .
a
Entry
L6 (mol%)
Yield (%)
endo:exo
ee (%)
1
2
3
4
1
5
10
20
5
99
99
99
99
88
96:4
96:4
97:3
95:5
–
39
55
25
17
0
b
5
a
Reaction condition: azachalcone 1 (6
mmol/L, 1.0 equiv.), 2 (30 mmol/L, 10
equiv.), GA-L6 catalyst (20 mol% of L6 according to 1), the reaction was carried out at
ꢀ
2
5 C for 20 h.
b
GA-L6 assembly was destroyed by addition of EtOH.
Fig. 2. The morphology of GA-L6 assembly in water, GA concentration was set as
1
wt% in the water. AFM images of GA-L6 the assembly with the molar ratio of L6 to
decreased when 10 mol% and 20 mol% L6 was co-assembled with
GA (entries 3 and 4). It seemed that the homogenous helical
assembly provided the high enantioselectivity. A control experi-
ment was carried out to clarify the key role of helical structures.
The addition of ethanol caused the destroying of helical architec-
ture of GA-L6 (Fig. S1 in Supporting information), correspondingly,
the resulted dispersion has no CD signal (Fig. S2 in Supporting
information) and only gave racemic product (entry 5). These
results indicated that self-assembled helical nanostructure was the
decisive factor for offering enantioselectivity.
GA: a) 1%, b) 5%, c) 10%, d) 20%. The inserted pictures in all the figures were the
optical photographs of assembly in the water. Scale bars: 200 nm.
which corresponded to the spectroscopic absorbance of phenan-
throline skeleton (Fig. 3, solid line), indicating that achiral L6
express induced chirality due to chiral alignment onto helical
nanofiber assembly.
Previously, helical DNA, protein and self-assembled nanotubes
have been utilized as chiral scaffolds for asymmetric catalysis after
interacting with cooper (II) complex [23–25]. In these cases, Diels-
Alder reaction was usually selected as benchmark reaction. Here,
for exploring the catalytic behavior of GA-L assemblies, Diels-Alder
reaction was also selected as a model reaction with azachalcone (1)
and cyclopentadiene (2) as substrates. GA-L6 was selected as a
model assembly for catalyzing Diels-Alder reaction. Due to the
helical assembled morphology was related to molar ratio of L6 to
GA, the catalytic behavior under various molar amount of L6 to GA
was first investigated, and the results were listed in Table 1. It was
found when 1 mol% of L6 was employed to co-assemble with GA,
The ligand effect for the reaction was further investigated, the
results were shown in Table 2. It was found that 27%–31% ee values
were obtained when Cu(NO ) , Cu(ClO ) and Cu(OAc) were
3 2 4 2 2
directly served as copper(II) complex (Table2, entries 1–3), while
bipyridine based assembly GA-L1 gave 31% ee (entry 4), and the
enantioselectivity slight increased when brominated bipyridine
based assembly GA-L2 was used as catalyst (entry 5). To our
surprise, the opposite enantioselectivity was obtained when
methoxyl substituted bipyridine co-assembled with GA (GA-L3,
entry 6), although the low ee value (7% ee) was obtained. The 49% ee
was achieved in the case of phenanthroline based ligand (GA-L4,
entry 7). The enantioselectivity decreased when methyl
39% ee was obtained (Table 1, entry 1), the ee value was increased
to 55% when the 5 mol% L6 was used (entry 2), the ee value
Please cite this article in press as: Y. Sun, et al., Glycyrrhizic acid based self-assembled helical nanostructures as scaffolds for asymmetric Diels-
Alder reaction, Chin. Chem. Lett. (2019), https://doi.org/10.1016/j.cclet.2019.02.015

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CCLET 4817 No. of Pages 3
Y. Sun et al. / Chinese Chemical Letters xxx (2019) xxx–xxx
3
Table 2
catalysis, and much more chiral supramolecular assemblies are
expected to apply in asymmetric catalysis.
a
Different ligands co-assembled with GA for catalysis of the Diels-Alder reaction .
Acknowledgments
The authors thank the National Natural Science Foundation of
China (Nos. 21861132002, 21773043) and Chinese Academy of
Sciences (Nos. XDB12020200, QYZDJ-SSW-SLH044) for the finan-
cial support.
Entry
Ligand-Cu2+
Cu(NO
Cu(ClO
Yield (%)
endo:exo
ee (%)
1
2
3
4
5
6
7
8
3
)
)
4 2
2
99
99
99
99
99
99
99
99
99
92
99
99
99
96:4
96:4
95:5
96:4
97:3
93:7
98:2
93:7
94:6
97:3
96:4
94:6
97:3
29
31
27
31
35
À7
49
37
55
61
5
Appendix A. Supplementary data
Cu(OAc)
GA-L1
GA-L2
GA-L3
GA-L4
GA-L5
GA-L6
GA-L6
GA-L6
GA-L6
GA-L6
2
Supplementary material related to this article can be
found, in the online version, at doi:https://doi.org/10.1016/j.
cclet.2019.02.015.
9
b
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1
0
c
1
1
d
1
2
27
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Please cite this article in press as: Y. Sun, et al., Glycyrrhizic acid based self-assembled helical nanostructures as scaffolds for asymmetric Diels-
Alder reaction, Chin. Chem. Lett. (2019), https://doi.org/10.1016/j.cclet.2019.02.015