Synthesis of functionalized copillar[4+1]arenes and rotaxane as heteromultivalent scaffolds

Article abstract of DOI:10.1039/d0cc07684h

In this study, novel copillar[4+1]arenes were used as central heteromultivalent scaffolds via orthogonal couplings with a series of biologically relevant molecules such as carbohydrates, α-amino acids, biotin and phenylboronic acid. Further modifications by introducing maleimides or cyclooctyne groups provided molecular probes adapted to copper-free click chemistry. An octa-azidated fluorescent rotaxane bearing two distinct ligands was also generated in a fully controlled manner.

Full text of DOI:10.1039/d0cc07684h

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DOI: 10.1039/D0CC07684H
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Synthesis of functionalized copillar[4+1]arenes and rotaxane as
heteromultivalent scaffolds
Wenzhang Chen,a Tharwat Mohy EI Dinea and Stéphane P. Vincenta
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
identical units, and the co-oligomerization of different monomers.1b,
In this study, novel copillar[4+1]arenes were used as central
heteromultivalent scaffolds via orthogonal couplings with a series
of biologically relevant molecules such as carbohydrates, α-amino
acids, biotin and phenylboronic acid. Further modifications by
introducing maleimides or cyclooctyne groups provided molecular
probes adapted to copper-free click chemistry. An octa-azidated
fluorescent rotaxane bearing two distinct ligands was also
generated in a fully controlled manner.
16 The latter strategy usually requires less synthetic steps and milder
reaction conditions, and provides better selectively. However, co-
oligomerization techniques have also some drawbacks as they highly
rely on the structural and electronic features of the monomers’
substituents which can dramatically affect the yield.17
R2
R2
O
R1
O
R1
O
R2
O
R1
O
R1
O
R2
O
R1
O
R1
O
R2
O
R2
O
R2
O
R1
O
R1
O
R1
O
Pillar[5]arenes were discovered in 2008 and quickly became a very
important class of macrocyclic compounds.1 Their unique topological
architecture has been exploited in host-guest chemistry,2 as
sensors,3 as light-harvesting systems,4 as separation and storage
crystals,5 in drug delivery and biological chemistry.6 For instance, our
group demonstrated, for the first time, that glycosylated
pillar[5]arenes could be exploited as competitors of the adhesion of
uropathogenic bacteria to eukaryotic cells.7 We then showed that
glyco-pillar[5]arenes8 as well as their rotaxanes9 were potent ligands
of bacterial lectins of Pseudomonas aeruginosa, a major human
pathogen. However, to the best of our knowledge glyco-
pillar[5]arenes10 have never been reported as antibiofilm agent of
this important human pathogen. In contrast, polycationic non-
glycosylated pillararenes have shown very interesting antibiofilm
properties, especially against Gram-positive pathogens.11
These studies also demonstrated that pillararenes are interesting
scaffolds for the preparation of heteromultivalent structures, which
can be exploited to probe complex biological phenomena.
Heteromultivalency is met when at least two structurally distinct
ligands are present on a central scaffold preferably in a topologically
controlled manner.12 Indeed, a non-regioselective functionalization
yields mixtures of constitutional isomers that are difficult to
O
O
R1
O
O
O
R1
O
R1
O
R1
R1
O
R1
O
R1
O
R1
R1
O
O
O
R1
O
O
R1
R1
R1
R2
R2
R1
A
B
C
Rim-differentiated
pillar[5]arene
Copillar[4+1]
arene
Pillar[5]arene-based
rotaxane
Figure 1. Generic structures of rim-differentiated pillar[5]arenes A,
copillar[4+1]arenes B and pillar[5]arene-based rotaxane C.
As a consequence, copillar[5]arenes reported to date are still
structurally limited to mostly alkyl and bromoalkyl substituents.16b
Although rather simple copillar[5]arenes have been used to
construct polymers,18 fluorescent switches19 and fluorescent
sensors,20 more advanced heteromutivalent scaffolds have never
been applied in chemical biology. Here, we demonstrate that co-
oligomerization is a versatile and selective technique to generate
copillar[4+1]arenes bearing distinct biologically relevant ligands
amenable to a broad range of applications in biological chemistry.
We also describe the preparation of a clickable fluorescent
heterovalent rotaxane.
First, we aimed at finding the optimal partners for the preparation
copillar[4+1]arenes using the co-oligomerization protocols reported
in the literature.15, 19a We selected bromide 217b, 21 as a key building
block to co-oligomerize with p- dialkoxy benzenes 1A -1F using
BF3.Et2O as catalyst (Scheme 1).17a, 17b The results showed that the
efficiency of the copillar[4+1]arene formation is extremely sensitive
to the structures of the two p-alkoxybenzenes. The best building
blocks for the co-oligomerization with 2 were 1D and 1F which
characterize.
One
strategy
to
achieve
regioselective
bisfunctionalization of pillar[5]arenes is the differentiation of the two
rims of these macromolecules (A, Figure 1),13,12a, 14 Another way to
display two distinct groups on a pillararene structure is to generate
copillars (B, Figure 1). In copillars, at least one of the hydroquinone
units bears different functional groups than the other ones.15
Heteromultivalency can also be achieved by exploiting the pillar’s
cavity to generate rotaxanes C (Figure 1). Two major strategies have
been developed for the preparation of copillar[5]arenes: the
modification of pre-synthesized homopillar[5]arenes bearing
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provided the corresponding copillar[4+1]arenes in 26% and 28% intermediate 6a (93% yield) which was further azidated in DMF to
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yields, respectively.
afford the clickable octa-mannoside 6 in 9D8O%I:y1i0e.l1d03(9S/cDh0eCmCe0716)8. 4DH-
mannose was selected because its multimers are competitors of the
infection by major human pathogens such as HIV and Ebola viruses.23
Br
Br
R1
R1
O
Table 1. Scope of functionalization of 6 with 7a-7h
O
O
(CH2O)n (53 eq.)
BF3.Et2O (17 eq.)
O
H
H
H
H
+
O
R1
O
DCE, rt, 1.5 h
R1
O
O
4
R1
2 1
/ X = 16/1
Ratio
2
1X
N
R
Br
R
N
Br
(yield = 26%)
E R1= -CH2(CH2)3CH=CH2 (yield<5%)
F R1= -CH2(CH2)4CH2Br (yield = 28%)
N
R
A R1= CH2CH2N3 (yield<5%)
B R1= CH2CH2OH (yield<5%)
C R1= Bn (yield = 11%)
1
1
1
D R1=
7a-h R1
O
1
1
1
R
C CH (3.2 eq.)
O
O
O
CuSO4 (0.2 eq.)
O
Na-ascorbate (0.66 eq.)
6
Scheme 1. Screening of the best building blocks 1X for the co-
oligomerization with 2
O
CH2Cl2/H2O, rt, 20 h
O
O
O
R
O
R
AcO
AcO
OAc
O
R
Next, we optimized conditions to generate copillar[5]arene 3 using
1D and 2 (Scheme 2 and Table S1). Among the catalysts usually used
for pillar[5]arene syntheses (FeCl3, methanesulfonic acid and
BF3.Et2O), BF3.Et2O gave the best yields. Interestingly, we found that
the concentration 2 had a dramatic impact on the yield. This
concentration effect may originate from the fact that the
pillar[5]arene formation is a dynamic process22 leading either to a
cyclized oligomer of a defined size or to polymers.
R
R
=
N
N
N
AcO
N
N
O
O
N
8a-h
R1
Product
8
Entry
1
R1CCH 7
R1
(Yield in %)a
OAc
O
7a
AcO
AcO
8a (91)
O
Br
Br
AcO
Br
Br
Br
OAc
O
O
O
O
OAc
O
O
AcO
AcO
O
(a)
2 1
O
2b
7b
7c
8b (93)
8c (98)
O
O
O
O
+
AcO
OAc
Ratio
/
D = 16/1
OAc
O
O
O
O
1D
O
O
2
O
O
Br
3b,c
O
Br
Br
Br
3
Br
(a)
2 1
/ D = 1/16
Ratio
H
O
S
N
4b,c
5
7d
7e
7f
8d (96)
8e (90)
8f (52)
N
R
R
Br
N3
AcO
AcO
O
OAc
O
R
O
O
O
R
O
O
O
AcO
O
O
O
O
O
N3
5
N
H
O
O
NHFmoc
(b)
(c)
O
O
O
O
H
H
H
H
N
O
O
N
6d
O
O
O
S
O
O
R
O
R
N
H
R
R
6
AcO
AcO
OAc
O
Br
N3
O
O
N
7b,c,e
7g
7h
8g (53)
8h (86)
N
R
=
AcO
N
N
H
4
Copillar[4+1]arene
O
N
O
O
O
B
O
O
Reagents and conditions: (a) BF3.Et2O (25.5 eq.), (CH2O)n (53 eq.),
DCE, rt, 1.5h, 40% yield for both reactions (b) 5 (10 eq.), Na-ascorbate
(0.2 eq.), CuSO4 (0.66 eq.), CH2Cl2/H2O, rt, 20 h, 93%. (c) NaN3 (6 eq.),
DMF, rt, 20 h, 98%.
8f
HN
(a) Isolated yield. (b) CuSO4 (0.4 eq.), Na-ascorbate (1.3 eq.). (c)
7c (5 eq.). (d) 7d (5 eq.), CuI (0.2 eq.), Et3N (0.4 eq.), DMF. (e)
7g (6 eq.). (f) CuI (0.2 eq.), TBTA (0.1 eq.), DMSO.
Scheme 2. Co-oligomerization of 1D with 2 and synthesis of octa-
mannosylated copillar[4+1]arene 6
The scope of functionalization of 6 with structurally diverse
molecules was then explored. Compound 6 was clicked to a series of
alkynes 7a-7h (Table 1). The efficient grafting of a second mono- or
di-saccharide yielded heterovalent structures 8a and 8b in 91% and
93% yields, respectively (Entries 1 and 2). The efficiency was also
excellent with fluorescent probes 7c and 7d (98% and 96% yields,
Entries 3-4). The coupling of ligand 7e proved that peptides can be
part of the repertoire of these novel glycosylated copillararenes (90%
yield, Table 1, Entry 5). Biotin 7f and maleimide 7g which are
extensively used in biochemistry, for instance to identify molecules
in complex biological media, were also efficiently clicked to 6
The optimal ratio between 1D and 2 was then investigated (Table S1)
and showed that 16 equivalents of 2 gave the best isolated yield.
Finally, we increased the number of BF3.Et2O equivalents to 25.5 eq.
which reproducibly provided an optimized 40% yield, including at a
larger scale (729 mg of 3). Importantly, by just inverting the ratio
between 1D and 2, we were able to obtain another clickable
copillar[4+1]arene 4, also in 40% yield, under the same reaction
conditions (Scheme 2). With copillar[4+1]arene 4 in hand, we carried
out the synthesis of the octa-mannosylated copillar[4+1]arene 6
(Scheme 2). Therefore, D-mannoside 5 (SI, S6) was clicked to
copillar[4+1]arene 4 using standard CuAAC conditions to provide
2 | J. Name., 2012, 00, 1-3
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furnishing 8f and 8g in moderate yields (Entries 6-7). Moreover, Finally, we wanted to determine whether those copillar[4+1]arenes
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boronates such as 7h, commonly exploited for the design of still maintain the host-guest properties that would further expand
DOI: 10.1039/D0CC07684H
biosensors were also successfully grafted to 6 (86% yield, Entry 8).24 their application scope. Therefore, we chose copillar[4+1]arene 3 to
However, the cycloaddition of compound 7f with 6 failed although investigate the synthesis of a clickable fluorescent rotaxane 16
the starting copillararene 6 was totally consumed. An alternative
O
N
11
S
O
O
protocol employing CuI as a catalyst in dry DMF allowed us to isolate
the desired product 8f in a moderate 52% yield (Entry 6).
Moreover, we wished to demonstrate that copillararene 8e bearing
two Fmoc-protected amino acids and 8 peracetylated mannosides
could be further functionalized by exploiting an orthogonal
deprotection and peptide couplings (Scheme 3). Consequently,
amine -8e was deprotected using DBU and cyclooctyne 9 was further
coupled to the intermediate bisamine using EDCI to yield the
copillarene 10 in 60% yield. Such a structure is interesting in chemical
biology as many applications of cell engineering require copper free
reactions.25
N
Br
N
N
O
N3
O
N
N
H
S
H
N
N
O
O
O
S
Br
N
N
N
N
O
(a)
O
H
O
3
O
Br
12
O
Br
Br
Br
O
N
N
O
N
Br
Br
O
O
N3
OAc
OAc
9
O
14
13 14
,
(b)
OAc
O
O
O
N
X
N
O
O
N
N
N
OAc
S
H
N
N
13
O
O
O
S
X
N
N
N
O
OAc
OAc
O
H
N
N
O
N
N
O
X
O
OAc
OAc
O
X
N
X
O
N
O
X
OAc
O
OAc
O
O
X
O
X
OAc
O
O
AcO
AcO
OAc
OAc
O
OAc
7a
NH
NHFmoc
HN
15
16
X
(
= Br)
= N3)
O
HN
(c)
(d)
17
X
(
O
O
N
R
N
R
R
R
N
N
N
R
N
Reagents and conditons: (a) 11 (2.4 eq.), CuSO4 (0.2 eq.), Na-
ascorbate (0.66 eq.), CH2Cl2/H2O, rt, 12 h, 94% (b) 12 (4 eq.), 13 (1.2
eq.), 14 (1 eq.), CuBr.SMe2 (2 eq.), CHCl3, -20 oC-rt, 12 h, 48%. (c) NaN3
(10 eq.), DMF, overnight, 97% (d) 7a (10 eq.), CuSO4 (0.2 eq.), Na-
ascorbate (0.66 eq.), CH2Cl2/H2O, rt, 20h, 79%.
R
O
O
R
R
O
O
O
O
(a)
(b)
O
O
O
O
OH
O
O
O
O
O
O
9
O
O
O
O
R
O
R
R
R
O
R
R
R
Scheme 4. Synthesis of clickable fluorescent rotaxane 16 and
octaglucosylated rotaxane 17.
R
N
N
N
H
H
N
N
N
HN
FmocHN
N
N
O
8e
O
10
O
O
(Scheme 4). Copillar[4+1]arene 3 was first labeled with a fluorescent
dansyl group 11 to yield 12 in 94% yield. Fucoside 13 was then clicked
to the supramolecular assembly of decyl-bisazide 14 and
copillararene 12 using CuBr.SMe2 to yield intermediate rotaxane 15
in a satisfactory yield of 48%. To the best of our knowledge,
rotaxanes constructed from a copillar[4+1]arene have been only
reported twice in the literature for applications in fluoride sensing.30
Rotaxane 16 was obtained by octa-azidation of 15 (Scheme 4). To
demonstrate that rotaxane 16 can be further functionalized, we
clicked it with an excess of 7a to obtain a new rotaxane 17 bearing
AcO
AcO
OAc
O
N
N
N
R
=
AcO
O
O
Reagent and conditions: (a) DBU (2.2 eq.), CH2Cl2, rt, 40 min. (b) EDCI
(3 eq.), 9 (3 eq.), CH2Cl2, rt, overnight, 60% over two steps.
Scheme 3. Synthesis of 10 bearing cyclooctynes ready for copper-
free click reactions-
We also proved that copillar[4+1]arene 3 can also be exploited to
generate heteromultivalent scaffolds (see SI Scheme S11). The issue
of the inherent planar chirality of pillararenes has been discussed in
the literature16b and applies to the molecules generated in this study
as carbohydrates are chiral ligands. Based on our own NMR study on
mannosylated pillar[5]arenes7 and the recent report of Sun et al.26
now 8 glucosides.
In conclusion, we have prepared two novel copillar[4+1]arenes 3 and
4 in 40% yield after screening a series of alkoxybenzenes and
optimized a procedure of cocyclization. This study revealed that the
concentration of the building blocks can strongly affect the
cocyclization yield. The two copillar[4+1]arenes were shown to be
versatile heteromultivalent platforms using CuAAC reaction
sequences to introduce orthogonal functional groups selected for
their applicability in chemical biology. Moreover, a fluorescent
rotaxane was constructed from an easily accessible
copillar[4+1]arene in a few steps, thus providing a tool that could be
further functionalized. Work is in progress to evaluate such
heterovalent copillar[4+1]arenes as lectin ligands with applications
who managed to isolate the two diasteroisomers of
a
decagalactosylated pillar[5]arenes and performed CD and NMR
analyses, it can be concluded that carbohydrates grafted to
pillar[5]arenes are bulky enough to prevent the oxygen-through-the-
annulus-rotation racemization mechanisms, even at high
temperature. Therefore, all the copillar[4+1]arenes and the
rotaxanes described in the present study are diastereomeric
mixtures. The complexity of the 1H and 13C-NMR of
copillar[4+1]arenes also arises from the loss of the D5 symmetry (as
compared to Pillar[5]arenes). In addition, 1H NMR spectra of
molecule 8c (See SI) were recorded at several temperatures and
showed that lowering the temperature at -5°C resulted in the
broadening of the signals whereas increasing the temperature to
55°C sharpened some of the signals. Noteworthy, all glycosylated
as antivirulence or antibiofilm agents or for multivalent enzyme
31
inhibition.28,
The fluorescent copillararenes and rotaxane
developed in this study are ideally suited for cell-based assays and in
vivo experiments, especially under copper-free conditions.
We would like to thank the China Scholarship Council (CSC, PhD
grant to WC) and CoFUND Move-In-Louvain (post-doctoral grant to
TMED).
pillar[5]arenes that have been designed to interact with lectins,8-10, 27
enzymes,28 bacteria,7,
or cancer cells29 have been assayed as
13
diastereomeric inseparable mixtures. To date, there is a single report
in the literature in which the two stereoisomers of a glycosylated
pillar[5]arene could be separated and characterized.26
Conflict of interest
The authors declare no competing financial interest
.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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A. Olson, H. Zuilhof and A. C. Sue, J. Am. Chem. Soc., 2018, 140,
Notes and references
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74-77.
DOI: 10.1039/D0CC07684H
1. (a) T. Ogoshi, S. Kanai, S. Fujinami, T. A. Yamagishi and Y. Nakamoto,
J. Am. Chem. Soc., 2008, 130, 5022-5023; (b) M. Xue, Y. Yang, X.
Chi, Z. Zhang and F. Huang, Acc. Chem. Res., 2012, 45, 1294-1308;
(c) H. Zhang, Z. Liu and Y. Zhao, Chem. Soc. Rev., 2018, 47, 5491-
5528.
2. (a) T. Ogoshi, S. Takashima and T. A. Yamagishi, J. Am. Chem. Soc.,
2018, 140, 1544-1548; (b) C. Li, Chem. Commun., 2014, 50, 12420-
12433.
3. (a) T. Kakuta, T. A. Yamagishi and T. Ogoshi, Acc. Chem. Res., 2018,
51, 1656-1666; (b) B. Shi, K. Jie, Y. Zhou, D. Xia and Y. Yao, Chem.
Commun., 2015, 51, 4503-4506; (c) M. Zuo, W. Qian, Z. Xu, W.
Shao, X. Y. Hu, D. Zhang, J. Jiang, X. Sun and L. Wang, Small, 2018,
14, 1801942; (d) Q. Li, H. Zhu and F. Huang, J. Am. Chem. Soc., 2019,
141, 13290-13294.
4. (a) B. Delavaux-Nicot, H. Ben Aziza, I. Nierengarten, T. Minh Nguyet
Trinh, E. Meichsner, M. Chesse, M. Holler, R. Abidi, E. Maisonhaute
and J. F. Nierengarten, Chem. Eur. J., 2018, 24, 133-140; (b) S. Guo,
Y. Song, Y. He, X. Y. Hu and L. Wang, Angew. Chem. Int. Ed., 2018,
57, 3163-3167; (c) C. L. Sun, H. Q. Peng, L. Y. Niu, Y. Z. Chen, L. Z.
Wu, C. H. Tung and Q. Z. Yang, Chem. Commun., 2018, 54, 1117-
1120.
5. (a) L. L. Tan, H. Li, Y. Tao, S. X. Zhang, B. Wang and Y. W. Yang, Adv.
Mater., 2014, 26, 7027-7031; (b) T. Ogoshi, R. Sueto, M. Yagyu, R.
Kojima, T. Kakuta, T. A. Yamagishi, K. Doitomi, A. K. Tummanapelli,
H. Hirao, Y. Sakata, S. Akine and M. Mizuno, Nat. Commun., 2019,
10, 479; (c) K. Jie, Y. Zhou, E. Li, R. Zhao, M. Liu and F. Huang, J.
Am. Chem. Soc., 2018, 140, 3190-3193.
6. (a) M. Barboiu and A. Gilles, Acc. Chem. Res., 2013, 46, 2814-2823;
(b) W. Feng, M. Jin, K. Yang, Y. Pei and Z. Pei, Chem. Commun.,
2018, 54, 13626-13640; (c) C. Sathiyajith, R. R. Shaikh, Q. Han, Y.
Zhang, K. Meguellati and Y. W. Yang, Chem. Commun., 2017, 53,
677-696; (d) T. Ogoshi, T. Kakuta and T. A. Yamagishi, Angew.
Chem. Int. Ed., 2019, 58, 2197-2206; (e) L. Gao, M. Li, S. Ehrmann,
Z. Tu and R. Haag, Angew. Chem. Int. Ed., 2019, 58, 3645-3649.
7. I. Nierengarten, K. Buffet, M. Holler, S. P. Vincent and J.-F.
Nierengarten, Tetrahedron Lett., 2013, 54, 2398-2402.
15. Z. Zhang, B. Xia, C. Han, Y. Yu and F. Huang, Org. Lett., 2010, 12,
3285-3287.
16. (a) W. Mao, S. Zhan, B. Zhu and D. Ma, J. Org. Chem., 2018, 83,
4147-4152; (b) T. Ogoshi, T. A. Yamagishi and Y. Nakamoto, Chem.
Rev., 2016, 116, 7937-8002; (c) T. F. Al-Azemi, M. Vinodh, F. H.
Alipour and A. A. Mohamod, Org. Biomol. Chem., 2018, 16, 7513-
7517; (d) T. F. Al-Azemi, M. Vinodh, F. H. Alipour and A. A.
Mohamod, RSC Adv., 2019, 9, 13814-13819.
17. (a) L. Liu, D. Cao, Y. Jin, H. Tao, Y. Kou and H. Meier, Org. Biomol.
Chem., 2011, 9, 7007-7010; (b) K. Wang, L. L. Tan, D. X. Chen, N.
Song, G. Xi, S. X. Zhang, C. Li and Y. W. Yang, Org. Biomol. Chem.,
2012, 10, 9405-9409; (c) L. Gao, Z. Zhang, S. Dong and M. Xue,
Macromol. Rapid Commun., 2014, 35, 987-991.
18. (a) X. Wang, K. Han, J. Li, X. Jia and C. Li, Polym. Chem., 2013, 4,
3998-4003; (b) T. Xiao and L. Wang, Tetrahedron lett., 2018, 59,
1172-1182; (c) Z. Zhang, Y. Luo, J. Chen, S. Dong, Y. Yu, Z. Ma and
F. Huang, Angew. Chem. Int. Ed., 2011, 50, 1397-1401.
19. (a) J. Bi, X. Zeng, D. Tian and H. Li, Org. Lett., 2016, 18, 1092-1095;
(b) J.-F. Chen, X.-B. Cheng, H. Li, Q. Lin, H. Yao, Y.-M. Zhang and
T.-B. Wei, New J. Chem., 2017, 41, 2148-2153.
20. (a) N. L. Strutt, R. S. Forgan, J. M. Spruell, Y. Y. Botros and J. F.
Stoddart, J. Am. Chem. Soc., 2011, 133, 5668-1571; (b) P. Wei, D.
Li, B. Shi, Q. Wang and F. Huang, Chem. Commun., 2015, 51,
15169-15172; (c) S. G. Roy, S. Mondal and K. Ghosh, New J. Chem.,
2020, 44, 5921-5928.
21. (a) I. Nierengarten, S. Guerra, M. Holler, J. F. Nierengarten and R.
Deschenaux, Chem. Commun., 2012, 48, 8072-8074; (b) Z. Zhang,
L. Shao and J. Yang, Tetrahedron Lett., 2018, 59, 3000-3004.
22. T. Ogoshi, N. Ueshima, F. Sakakibara, T.-a. Yamagishi and T. Haino,
Org. Lett., 2014, 16, 2896-2899.
23. A. Muñoz, D. Sigwalt, B. M. Illescas, J. Luczkowiak, L. Rodríguez-
Pérez, I. Nierengarten, M. Holler, J.-S. Remy, K. Buffet, S. P. Vincent,
J. Rojo, R. Delgado, J.-F. Nierengarten and N. Martín, Nat. Chem.,
2016, 8, 50-57.
24. B. Akgun and D. G. Hall, Angew.Chem. Int. Ed., 2018, 57, 13028-
13044.
25. (a) K. Poncin, A. Roba, R. Jimmidi, G. Potemberg, A. Fioravanti, N.
Francis, K. Willemart, N. Zeippen, A. Machelart, E. G. Biondi, E.
Muraille, S. P. Vincent and X. De Bolle, Nat. Commun., 2019, 10,
4847; (b) E. M. Sletten and C. R. Bertozzi, Acc. Chem. Res., 2011,
44, 666-676.
8. K. Buffet, I. Nierengarten, N. Galanos, E. Gillon, M. Holler, A.
Imberty, S. E. Matthews, S. Vidal, S. P. Vincent and J. F.
Nierengarten, Chem. Eur. J., 2016, 22, 2955-2963.
9. S. P. Vincent, K. Buffet, I. Nierengarten, A. Imberty and J. F.
Nierengarten, Chem. Eur. J., 2016, 22, 88-92.
10. N. Galanos, E. Gillon, A. Imberty, S. E. Matthews and S. Vidal, Org.
Biomol. Chem., 2016, 14, 3476-3481.
11. (a) R. Joseph, D. Kaizerman, I. M. Herzog, M. Hadar, M. Feldman,
M. Fridman, Y. Cohen, Chem. Commun. 2016, 52, 10656−10659;
(b) R. Joseph, A. Naugolny, M. Feldman, I. M. Herzog, M. Fridman
and Y. Cohen, J. Am. Chem. Soc., 2016, 138, 754-757.
26. G. Sun, L. Pu, S. Pangannaya, T. Xiao, X. Y. Hu, J. Jiang and L. Wang,
Front. Chem., 2019, 7, 743.
27. P. Wei, J. A. Czaplewska, L. Wang, S. Schubert, J. C. Brendel and
U. S. Schubert, ACS Macro Lett., 2020, 9, 540-545.
28. A. Tikad, H. Fu, C. M. Sevrain, S. Laurent, J. F. Nierengarten and S.
P. Vincent, Chem. Eur. J., 2016, 22, 13147-13155.
12. (a) J. L. Jimenez Blanco, C. Ortiz Mellet and J. M. Garcia Fernandez,
Chem. Soc. Rev., 2013, 42, 4518-4531; (b) D. Ponader, P. Maffre, J.
Aretz, D. Pussak, N. M. Ninnemann, S. Schmidt, P. H. Seeberger, C.
Rademacher, G. U. Nienhaus and L. Hartmann, J. Am. Chem. Soc.,
2014, 136, 2008-2016; (c) C. Muller, G. Despras and T. K. Lindhorst,
Chem. Soc. Rev., 2016, 45, 3275-3302; (d) H. K. Choi, D. Lee, A.
Singla, J. S. Kwon and H. J. Wu, Glycobiology, 2019, 29, 397-408.
13. G. Yu, Y. Ma, C. Han, Y. Yao, G. Tang, Z. Mao, C. Gao and F. Huang,
J. Am. Chem. Soc., 2013, 135, 10310-30313.
29. (a) X. Liu, W. Shao, Y. Zheng, C. Yao, L. Peng, D. Zhang, X. Y. Hu
and L. Wang, Chem. Commun., 2017, 53, 8596-8599; (b) X. Wu, Y.
Zhang, Y. Lu, S. Pang, K. Yang, Z. Tian, Y. Pei, Y. Qu, F. Wang and Z.
Pei, J. Mater. Chem. B, 2017, 5, 3483-3487.
30. (a) Z. Zhang, C. Han, G. Yu and F. Huang, Chem. Sci., 2012, 3, 3026-
3031; (b) Q. Li, Y. Wu, Y. Liu, L. Shangguan, B. Shi and H. Zhu, Org.
Lett., 2020, 22, 6662-6666.
31. (a) K. Buffet, E. Gillon, M. Holler, J.-F. Nierengarten, A. Imberty
and S. P. Vincent, Org. Biomol. Chem., 2015, 13, 6482-6492; (b) M.
Abellán-Flos, M. Tanç, C. T. Supuran and S. P. Vincent, Org. Biomol.
Chem., 2015, 13, 7445-7451.
14. (a) P. Demay-Drouhard, K. Du, K. Samanta, X. Wan, W. Yang, R.
Srinivasan, A. C. Sue and H. Zuilhof, Org. Lett., 2019, 21, 3976-3980;
(b) M. Guo, X. Wang, C. Zhan, P. Demay-Drouhard, W. Li, K. Du, M.
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