Synthesis of Cyclotriveratrylene-Sucrose-Based Capsules

Article abstract of DOI:10.1021/acs.orglett.9b02451

Cyclotriveratrylene (CTV) is a C₃-symmetrical macrocycle, which can be used as a chiral building block in the construction of supramolecular containers. Coupling of the CTV unit with a sucrose molecule gave enantiopure water-soluble (after depr

Full text of DOI:10.1021/acs.orglett.9b02451

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Synthesis of Cyclotriveratrylene-Sucrose-Based Capsules
Łukasz Szyszka, Piotr Cmoch, Aleksandra Butkiewicz, Mykhaylo A. Potopnyk,*
and Sławomir Jarosz*
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
S
* Supporting Information
ABSTRACT: Cyclotriveratrylene (CTV) is a C3-symmetrical macrocycle, which can be used as a chiral building block in the
construction of supramolecular containers. Coupling of the CTV unit with a sucrose molecule gave enantiopure water-soluble
(after deprotection) containers. The absolute configuration of the synthesized capsules was determined by NMR and ECD
spectroscopies and DFT calculations.
hiral molecular containers play an important role in
which is synthesized as a racemic compound. This requires the
Csupramolecular chemistry, due to their high ability for resolution of a racemic mixture by HPLC that can, in some
cases, provide only a small amount of the desired enantiopure
product.10d,17 Another method requires an introduction of a
chiral fragment to form diastereomers; however, their
separations are usually difficult.10c,12c,18
stereoselective discrimination of chiral guests, which can lead
to a better understanding of recognition phenomena by
biological receptors.1 Molecular containers, based on the
cyclotriveratrylene (CTV) building block, have been recently
extensively studied.2 Cyclotriveratrylene is a C3-symmetrical
macrocyclic compound with a rigid bowl-shaped, electron-rich,
and lipophilic cavity in which the guest molecules can be
bound noncovalently. This building block is effectively used for
the construction of various host molecules due to its small
cavity, stable conformation, and easy functionalization.3 While
the combination of two CTV derivatives, linked together, give
molecular capsules named cryptophanes, the CTV derivatives
connected with another C3-symmetrical unit provide hemi-
cryptophanes.2
The CTV-based molecular hosts gained much attention in
recent decades, due to their selective complexing properties
toward neutral or charged guests (metals,4 fullerenes,5
xenone,6 and small organic compounds such as epoxides,7
halogenomethanes,8 ammonium salts,9 carbohydrates,10 neuro-
transmitters,9b,11 or zwitterions12). The CTV macrocycles find
an application as materials for dendrimers,13 gelators,14 or
nanostructures.15 Many of complexation experiments have
been studied in organic media,1 while most of recognition
phenomena in nature takes place in water.16 Thus, the design
of water-soluble molecular receptors is an important challenge
in supramolecular chemistry.
Carbohydrates, being one of the most information-rich
biological molecules due to the presence of numerous
stereogenic centers, can be successfully used as chiral building
blocks in the construction of supramolecular receptors.19
Sucrose is the cheapest chiral, optically pure available
material.20 Commercial sucrose has a very high purity
(>99.9%) making it one of the purest organic substances
produced on an industrial scale.21 Introducing sugars to a CTV
platform can provide CTV with high water solubility.22
The combination of a CTV moiety with several sugars has
been reported in the literature.22b,23 Han et al. described the
water-soluble CTV-based glycoconjugates containing periph-
eral glucoside and lactoside units, which are able to complex
fullerene C60.22b Chambron et al. obtained a pair of
diastereomers based on an α-cyclodextrin and CTV unit.18b
However, these targets were obtained in very low yields (8%
and 5%, 6:1 ratio respectively). Moreover, the main
diastereomer was solvent-sensitive.24 This group also synthe-
sized α-cyclodextrin hemicryptophane containing disulfide
bonds in 11% yield as a 5:3 mixture of two diastereomers
that could not be separated.18c
Most of cyclotriveratrylene-based containers have been
obtained as racemic mixtures due to the CTV substrate
Received: July 15, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02451
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Several different classes of sucrose-based macrocyclic
compounds, including crown25 and aza-crown26 derivatives,
macrocyclic dilactams,27 ureas and thioureas,28 were previously
prepared in our laboratory. They were used as effective chiral
supramolecular receptors for cations and anions.25,26,28
Herein, we present the synthesis of novel water-soluble
CTV-based molecular containers with a sucrose moiety. These
compounds are the first molecular cages obtained from CTV
and sucrose platforms.
Scheme 2. Synthesis of Capsules M-9 and P-9
The synthesis of this type of molecular containers was
initiated from commercial sucrose (1), which was converted, in
a three-step synthesis, into 2,3,3′,4,4′-penta-O-benzyl deriva-
tive 3. We decided to choose the benzyl protection for five
secondary hydroxyl groups because they can be easily removed
under hydrogenation conditions. The protection of the
primary hydroxyls with bulky silyl groups, followed by
protection of the remaining secondary hydroxyl groups as
benzyl ethers, gave fully protected sucrose 2 in 36% overall
yield. Removal of temporary silyl blocks provided sucrose
derivative 3 in good yield (78%). To connect both CTV and
sucrose units, the terminal C-6, C-1′, and C-6′ positions were
elongated by oxyethyl chains. This was achieved by an
alkylation of compound 3 under phase-transfer catalytic
conditions (PTC) with tert-butyl bromoacetate which
provided triester 4 in 56% yield. Reduction of the ester groups
gave triol 5 (90%), which was subsequently transformed into
tri-iodide 6 under the Garegg−Samuelsson iodination
conditions in very good yield (85%) (Scheme 1).
Table 1. Coupling Reaction Optimization Conditions
c
entry
base
solvent
temp [°C]
time [h]
yield [%]
a
d
1
2
3
4
5
6
7
8
9
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
acetone
acetone
MeCN
MeCN
rt
reflux
rt
reflux
reflux
rt
80
reflux
reflux
72
72
72
72
96
72
48
72
72
N/A
23
N/A
27
a
a
d
a
a
d
EtCN
DMF
DMF
N/A
a
21
14
22
33
a
a
MeCN
MeCN
Scheme 1. Synthesis of Sucrose Triiodide 6
b
Cs2CO3
a
b
c
c = 0.002 M. c = 0.001 M. Total yield for two diastereomers P and
d
M (ratio ∼1:1) after column chromatography. N/A: no reaction.
days in refluxing conditions). The change of the solvent to
more polar (DMF) gave 21% of the total yield at room
temperature. However, the increase of the temperature to 80
°C causes a decrease of the reaction yield (14%). Thus,
acetonitrile was selected as the best solvent for the cyclization
reaction. We also tested potassium carbonate under analogous
conditions; we observed, however, reduction of the reaction
yield (22%). We tested this reaction under more diluted
conditions (c = 0.001 M) and obtained the products M-8/P-8
in a slightly higher (33%) total yield. It is clearly evident that
more diluted conditions gave, as expected, a higher yield of
both diastereomers (Table 1). In all cases, the ratios of
products M-8/P-8 were approximately 1:1.
The benzyl ether protections were removed by palladium-
catalyzed hydrogenation, and the individual diastereomers M-8
and P-8 were transformed into water-soluble compounds M-9
and P-9, respectively, in quantitative yields (Scheme 2). The
solubility of both unprotected capsules (M-9 and P-9) is
approximately 6 mg/1 mL at room temperature.
The characterization of all the synthesized compounds was
performed by NMR (1H, 13C) spectroscopy and high-
resolution mass spectrometry. The structures of all synthesized
sucrose derivatives were determined by interpretation of the
one-dimension (1H, 13C), two-dimension homonuclear
(1H−1H COSY), and heteronuclear (1H−13C HSQC and
HMBC) NMR spectra.
Cyclotriguaiacylene (7) was prepared as a racemic
compound according to a modified literature procedure29
(see Supporting Information). Coupling of both species (6 and
rac-7) under the basic conditions afforded two diastereomeric
molecular containers M-8 and P-8 (Scheme 2). The
optimization of the reaction conditions is shown in Table 1.
Cesium carbonate was selected as the effective base. At room
temperature in acetone and acetonitrile medium, the formation
of the products was not observed. However, after heating the
reaction mixture for 3 days, the products M-8/P-8 were
isolated in 23% and 27% total yields from acetone and
acetonitrile medium, respectively. The reaction in propionitrile
medium was not successful (no product formation even after 4
In the case of capsules M-8 and P-8, additionally the
ROESY, TOCSY, and HSQC-TOCSY NMR spectra were
recorded and the analysis of all NMR data allowed assignment
B
DOI: 10.1021/acs.orglett.9b02451
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
of the spatial position of protons and determination of the
structures of both enantiomers. All COSY, TOCSY, and
ROESY effects not only allowed for the exact assignment of the
protons of sucrose and CTV moieties but also made possible
to establish the spatial arrangements of phenyl, methylene, and
methylylidene protons of both moieties.
In spite of the very close position of the signals for the
protons of methoxy groups in both isomeric structures M-8
and P-8 (ca. 3.60−3.80 ppm), cross-peaks in the ROESY
spectra (Figure 1) unambiguously point to the specific
same numbering in isomers M-8 and P-8 respectively, also
have different chemical shifts depending on their spatial
arrangement in the specific molecule. Most significant
differences between spectra of capsules M-8 and P-8 were
observed for pairs of protons H-6a/H-6b and H-6′a/H-6′b (ca.
0.3−0.5 ppm), as well as for protons H-3′, H-4′, H-5′, and H-5
(ca. 0.1−0.4 ppm).
In the case of carbon resonances these changes are smaller
and not so clear for aliphatic carbons as for protons but still
significant. For compound P-8, the aliphatic carbons: C-5, C-6,
C-2′, C-4′, and C-5′ are more shielded than the appropriate
carbons in isomer M-8 by ca. 0.5−2.0 ppm, whereas the
strongest changes are observed for the C-4′ and C-5′.
Significant changes in nuclei shieldings were also observed
for carbons C-7′ and C-8′′ in such a way that passing from P-8
to M-8 causes carbon shielding to increase by ca. 3.0 ppm for
C-7′ and simultaneously shielding to decrease by ca. 3.5 ppm
for C-8′′. For aromatic carbons of rings A, B, and C, especially
positions C-11, C-11′′ and C-12, C-12′′, several changes (ca.
1−2 ppm) related to the spatial arrangement of rings A/B and
C are observed.
The M/P configuration of capsules 8 was additionally
studied by the electronic circular dichroism (ECD) spectros-
copy supported by the density functional theory (DFT)
calculations. Such an approach was successfully applied for
both configuration and conformation analysis of various
compounds30 and also for the C1-cyclotriveratrylene deriva-
tives.31 The ECD spectra of solutions of diastereomers M-8
and P-8 in acetonitrile showed almost mirror images, and the
most intense bands centered at ca. 230, 250, and 290 nm
exhibited a bisignate pattern (Figure 2). The ECD spectra of
1
Figure 1. H−13C NMR ROESY spectra of compounds M-8 (top)
and P-8 (down) demonstrated steric interactions between anomeric
hydrogen (H-1) and hydrogen atoms from methoxy groups.
structures (M-8 and P-8). In the case of isomer M-8, the
anomeric proton at δ = 5.26 ppm strongly interacts with the
methyl protons of the OCH3 group (H-16′′) at 3.79 ppm at
ring B of the CTV substituent, whereas the proton at 4.93 ppm
in P-8 shows a similar effect with OCH3 protons (H-16) at
3.77 ppm at ring A (Figure 1).
Figure 2. Comparison of experimental (solid lines) and simulated
(dashed lines) ECD spectra of capsules M-8 and P-8 measured in
MeCN. In simulations, the CAM-B3LYP/SVP/PCM(MeCN)
computational level was applied.
1
Analysis of the 13C and especially H NMR chemical shifts
for appropriate proton and carbon atoms in both isomeric
structures strongly indicates the following changes. The
position of the protons of the OCH3 group just above the
anomeric proton (in compound P-8) causes its relatively
strong shielding to increase by ca. 0.3 ppm as compared to its
position in isomer M-8. Moreover, the position of the OCH3
group in capsule P-8 causes additional shielding increase of
protons H-1′a and H-1′b by ca. 0.2−0.5 ppm compared to
their positions in compound M-8. All other protons with the
capsules M-8 and P-8 are in line with the results obtained for
M or P stereodescriptors of the C3-CTV analogs bearing two
O-alkyl groups (OR, OCOR) for which exciton couplings were
observed at ca. 220, 240, and 290 nm.32 Moreover, the band
sign sequence was analogous for all molecules of the same M
or P conformation.
For a better understanding of the spectral properties of the
investigated capsules, DFT computational studies were
performed. Geometrical structures of compounds M-8 and
C
DOI: 10.1021/acs.orglett.9b02451
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ORCID
P-8 were optimized, and the ECD spectra were simulated at
the CAM-B3LYP/SVP/PCM level with the addition of the
acetonitrile solvent effect utilizing the integral-equation-
formalism polarizable continuum model (IEFPCM) (for
details see the Supporting Information). The simulated ECD
spectra of compounds M-8 and P-8 showed satisfactory
compliance with the experiment (Figure 2). Therefore, the M/
P assignment of capsules 8 performed by ECD spectroscopy is
in line with the NMR conclusions.
Piotr Cmoch: 0000-0002-8413-9290
Mykhaylo A. Potopnyk: 0000-0002-4543-2785
Sławomir Jarosz: 0000-0002-9212-6203
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The optimized structures of capsules M-8 and P-8 (Figure
3) clearly show the different position of the glucose unit in
We would like to acknowledge Poland’s National Science
Centre (UMO-2016/21/B/ST5/03382) for financial support.
We also thank PLGrid Infrastructure for the computer time.
REFERENCES
■
(1) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry, 2nd ed.;
Wiley-VCH: Weinheim, 2009.
(2) Zhang, D.; Martinez, A.; Dutasta, J.-P. Emergence of
Hemicryptophanes: From Synthesis to Applications for Recognition,
Molecular Machines, and Supramolecular Catalysis. Chem. Rev. 2017,
117, 4900−4942.
(3) (a) Hardie, M. J. Recent advances in the chemistry of
cyclotriveratrylene. Chem. Soc. Rev. 2010, 39, 516−527. (b) Henkelis,
J. J.; Hardie, M. J. Controlling the assembly of cyclotriveratrylene-
derived coordination cages. Chem. Commun. 2015, 51, 11929−11943.
(4) (a) Makita, Y.; Sugimoto, K.; Furuyoshi, K.; Ikeda, K.; Fujiwara,
S.; Shin-ike, T.; Ogawa, A. A Zinc(II)-Included Hemicryptophane:
Facile Synthesis, Characterization, and Catalytic Activity. Inorg. Chem.
2010, 49, 7220−7222. (b) Brotin, T.; Montserret, R.; Bouchet, A.;
Cavagnat, D.; Linares, M.; Buffeteau, T. High Affinity of Water-
Soluble Cryptophanes for Cesium Cations. J. Org. Chem. 2012, 77,
1198−1201. (c) Schmitt, A.; Collin, S.; Bucher, C.; Maurel, V.;
Dutasta, J.-P.; Martinez, A. Synthesis and physico-chemical properties
of the first water soluble Cu(II)@hemicryptophane complex. Org.
Biomol. Chem. 2015, 13, 2157−2161. (d) Gosse, I.; Robeyns, K.;
Bougault, C.; Martinez, A.; Tinant, B.; Dutasta, J.-P. Synthesis and
Structural Studies of Gallium(III) and Iron(III) Hemicryptophane
Complexes. Inorg. Chem. 2016, 55, 1011−1013. (e) Zhang, D.;
Bousquet, B.; Mulatier, J.-C.; Pitrat, D.; Jean, M.; Vanthuyne, N.; Guy,
L.; Dutasta, J.-P.; Martinez, A. Synthesis, Resolution, and Absolute
Configuration of Chiral Tris(2-pyridylmethyl)amine-Based Hemi-
cryptophane Molecular Cages. J. Org. Chem. 2017, 82, 6082−6088.
(5) (a) Huerta, E.; Metselaar, G. A.; Fragoso, A.; Santos, E.; Bo, C.;
de Mendoza, J. Selective Binding and Easy Separation of C70 by
Nanoscale Self-Assembled Capsules. Angew. Chem., Int. Ed. 2007, 46,
Figure 3. DFT structures of compounds M-8 and P-8 (for clear view
all hydrogen atoms, except the anomeric one, are not shown).
both compounds, which apparently is caused by steric
intermolecular interaction with the corresponding CTV
moiety. As shown in Figure 3, the anomeric hydrogen atom
(H-1) of compound M-8 is oriented outside the molecular
cavity. In contrast, the corresponding atom in structure P-8 is
located inside the cavity. These geometrical data explain the
difference in the NMR spectra: the anomeric hydrogen atom in
the structure P-8 is shielded by the molecular cavity, causing
the corresponding shift in the 1H NMR spectrum. These
observations additionally confirm the NMR and ECD
identification of diastereomers M-8 and P-8.
In summary, we have developed the simple synthetic route
to the first enantiopure cyclotriveratrylene-sucrose-based
capsules via an alkylation of racemic cyclotriguaiacylene (7)
with tri-iodo sucrose derivative 6. The approach presented
here may open the possibility to prepare chiral CTV-sucrose
molecular containers with different sizes depending on the
need.
́
202−205. (b) Huerta, E.; Isla, H.; Perez, E. M.; Bo, C.; Martin, N.; de
Mendoza, J. Tripodal exTTF-CTV Hosts for Fullerenes. J. Am. Chem.
Soc. 2010, 132, 5351−5353. (c) Wang, L.; Wang, G.-T.; Zhao, X.;
Jiang, X.-K.; Li, Z.-T. Hydrogen Bonding-Directed Quantitative Self-
Assembly of Cyclotriveratrylene Capsules and Their Encapsulation of
C60 and C70. J. Org. Chem. 2011, 76, 3531−3535. (d) Li, M.-J.;
Huang, C.-H.; Lai, C.-C.; Chiu, S.-H. Hemicarceplex Formation With
a Cyclotriveratrylene-Based Molecular Cage Allows Isolation of High-
Purity (≥99.0%) C70 Directly from Fullerene Extracts. Org. Lett. 2012,
14, 6146−6149. (e) Liu, K.-S.; Li, M.-J.; Lai, C.-C.; Chiu, S.-H.
Incarceration of Higher-Order Fullerenes within Cyclotriveratrylene-
Based Hemicarcerands Allows Selective Isolation of C76, C78, and C84
from a Commercial Fullerene Mixture. Chem. - Eur. J. 2016, 22,
17468−17476.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02451.
Experimental procedures and characterization of all
synthesized compounds; UV and ECD spectra and
optimized geometry for compounds M-8 and P-8; NMR
spectra of all synthesized compounds; HRMS spectra of
compounds M-8, P-8, M-9, and P-9 (PDF)
(6) (a) Bartik, K.; Luhmer, M.; Dutasta, J.-P.; Collet, A.; Reisse, J.
1
129Xe and H NMR Study of the Reversible Trapping of Xenon by
Cryptophane-A in Organic Solution. J. Am. Chem. Soc. 1998, 120,
784−791. (b) Huber, J. G.; Brotin, T.; Dubois, L.; Desvaux, H.;
Dutasta, J.-P.; Berthault, P. Water Soluble Cryptophanes Showing
Unprecedented Affinity for Xenon: Candidates as NMR-Based
Biosensors. J. Am. Chem. Soc. 2006, 128, 6239−6246. (c) Wei, Q.;
Seward, G. K.; Hill, P. A.; Patton, B.; Dimitrov, I. E.; Kuzma, N. N.;
Dmochowski, I. J. Designing 129Xe NMR Biosensors for Matrix
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: potopnyk@gmail.com.
*E-mail: slawomir.jarosz@icho.edu.pl.
D
DOI: 10.1021/acs.orglett.9b02451
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Metalloproteinnase Detection. J. Am. Chem. Soc. 2006, 128, 13274−
13283. (d) Hill, P. A.; Wei, Q.; Eckenhoff, R.; Dmochowski, I. J.
Thermodynamics of Xenon Binding to Cryptophane in Water and
Human Plasma. J. Am. Chem. Soc. 2007, 129, 9262−9263. (e) Hill, P.
A.; Wei, Q.; Troxler, T.; Dmochowski, I. J. Substituent Effects on
Xenon Binding Affinity and Solution Behavior of Water-Soluble
Cryptophanes. J. Am. Chem. Soc. 2009, 131, 3069−3077.
(f) Chambers, J. M.; Hill, P. A.; Aaron, J. A.; Han, Z.; Christianson,
D. W.; Kuzma, N. N.; Dmochowski, I. J. Cryptophane Xenon-129
Nuclear Magnetic Resonance Biosensors Targeting Human Carbonic
Anhydrase. J. Am. Chem. Soc. 2009, 131, 563−569. (g) Fairchild, R.
M.; Joseph, A. I.; Holman, K. T.; Fogarty, H. A.; Brotin, T.; Dutasta,
J.-P.; Boutin, C.; Huber, G.; Berthault, P. A Water-Soluble Xe@
cryptophane-111 Complex Exhibits Very High Thermodynamic
Stability and a Peculiar 129Xe NMR Chemical Shift. J. Am. Chem.
Soc. 2010, 132, 15505−15507.
(7) (a) Bouchet, A.; Brotin, T.; Linares, M.; Ågren, H.; Cavagnat,
D.; Buffeteau, T. Enantioselective Complexation of Chiral Propylene
Oxide by an Enantiopure Water-Soluble Cryptophane. J. Org. Chem.
2011, 76, 4178−4181. (b) Bouchet, A.; Brotin, T.; Linares, M.;
Cavagnat, D.; Buffeteau, T. Influence of the Chemical Structure of
Water-Soluble Cryptophanes on Their Overall Chiroptical and
Binding Properties. J. Org. Chem. 2011, 76, 7816−7825.
Mulatier, J.-C.; Dutasta, J.-P.; Guy, L.; Martinez, A. Large-Scale
Synthesis of Enantiopure Molecular Cages: Chiroptical and
Recognition Properties. Chem. - Eur. J. 2016, 22, 2068−2074.
(12) (a) Perraud, O.; Robert, V.; Martinez, A.; Dutasta, J.-P. A
Designed Cavity for Zwitterionic Species: Selective Recognition of
Taurine in Aqueous Media. Chem. - Eur. J. 2011, 17, 13405−13408.
(b) Perraud, O.; Robert, V.; Gornitzka, H.; Martinez, A.; Dutasta, J.-P.
Combined Cation−π and Anion−π Interactions for Zwitterion
Recognition. Angew. Chem., Int. Ed. 2012, 51, 504−508. (c) Cochrane,
J. R.; Schmitt, A.; Wille, U.; Hutton, C. A. Synthesis of cyclic peptide
hemicryptophanes: enantioselective recognition of a chiral zwitter-
ionic guest. Chem. Commun. 2013, 49, 8504−8506.
(13) (a) Eckert, J.-F.; Byrne, D.; Nicoud, J.-F.; Oswald, L.;
Nierengarten, J.-F.; Numata, M.; Ikeda, A.; Shinkai, A.; Armaroli, N.
Polybenzyl ether dendrimers for the complexation of [60] fullerenes.
New J. Chem. 2000, 24, 749−758. (b) Rio, Y.; Nierengarten, J.-F.
Water soluble supramolecular cyclotriveratrylene−[60]fullerene com-
plexes with potential for biological applications. Tetrahedron Lett.
2002, 43, 4321−4324. (c) Lijanova, I. V.; Flores Maturano, J.;
́
́
Domínguez Chavez, J. G.; Sanchez Montes, K. E.; Hernandez Ortega,
S.; Klimova, T.; Martínez-García, M. Synthesis of cyclotriveratrylene
dendrimers and their supramolecular complexes with fullerene C60.
Supramol. Chem. 2009, 21, 24−34.
(8) (a) Canceill, J.; Lacombe, L.; Collet, A. Analytical Optical
Resolution of Bromochlorofluoromethane by Enantioselective In-
clusion into a Tailor-Made “Cryptophane” and Determination of Its
Maximum Rotation. J. Am. Chem. Soc. 1985, 107, 6993−6996.
(b) Costante-Crassous, J.; Marrone, T.; Briggs, J. M.; McCammon, J.
A.; Collet, A. Absolute Configuration of Bromochlorofluoromethane
from Molecular Dynamics Simulation of Its Enantioselective
Complexation by Cryptophane-C. J. Am. Chem. Soc. 1997, 119,
3818−3823. (c) Soulard, P.; Asselin, P.; Cuisset, A.; Moreno, J. R. A.;
Huet, T. R.; Petitprez, D.; Demaison, J.; Freedman, T. B.; Cao, X.;
Nafiec, L. A.; Crassous, J. Chlorofluoroiodomethane as a potential
candidate for parity violation measurements. Phys. Chem. Chem. Phys.
2006, 8, 79−92.
(9) (a) Perraud, O.; Lefevre, S.; Robert, V.; Martinez, A.; Dutasta, J.-
P. Hemicryptophane host as efficient primary alkylammonium ion
receptor. Org. Biomol. Chem. 2012, 10, 1056−1059. (b) Makita, Y.;
Katayama, N.; Lee, H.-H.; Abe, T.; Sogawa, K.; Nomoto, A.; Fujiwara,
S.; Ogawa, A. A tri-aromatic amide hemicryptophane host: synthesis
and acetylcholine binding. Tetrahedron Lett. 2016, 57, 5112−5115.
(10) (a) Schmitt, A.; Perraud, O.; Payet, E.; Chatelet, B.; Bousquet,
B.; Valls, M.; Padula, D.; Di Bari, L.; Dutasta, J.-P.; Martinez, A.
Improved hemicryptophane hosts for the stereoselective recognition
of glucopyranosides. Org. Biomol. Chem. 2014, 12, 4211−4217.
(b) Lefevre, S.; Simonet, R.; Pitrat, D.; Mulatier, J.-C.; Vanthuyne, N.;
Jean, M.; Dutasta, J. P.; Guy, L.; Martinez, A. Closed vs Open-Shell
CTV Based Host Compounds: A Direct Comparison. ChemistrySelect
2016, 1, 6316−6320. (c) Zhang, D.; Mulatier, J.-C.; Cochrane, J. R.;
Guy, L.; Gao, G.; Dutasta, J.-P.; Martinez, A. Helical, Axial, and
Central Chirality Combined in a Single Cage: Synthesis, Absolute
Configuration, and Recognition Properties. Chem. - Eur. J. 2016, 22,
8038−8042. (d) Long, A.; Perraud, O.; Albalat, M.; Robert, V.;
Dutasta, J.-P.; Martinez, A. Helical Chirality Induces a Substrate-
Selectivity Switch in Carbohydrates Recognitions. J. Org. Chem. 2018,
83, 6301−6306.
(14) (a) Bardelang, D.; Camerel, F.; Ziessel, R.; Schmutz, M.;
Hannon, M. J. New organogelators based on cyclotriveratrylene
platforms bearing 2-dimethylacetal-5-carbonylpyridine fragments. J.
Mater. Chem. 2008, 18, 489−494. (b) Cai, F.; Shen, J.-S.; Wang, J.-H.;
Zhang, H.; Zhao, J.-S.; Zeng, E.-M.; Jiang, Y.-B. Hydrogelators of
cyclotriveratrylene derivatives. Org. Biomol. Chem. 2012, 10, 1418−
1423.
(15) (a) Xu, D.; Warmuth, R. Edge-Directed Dynamic Covalent
Synthesis of a Chiral Nanocube. J. Am. Chem. Soc. 2008, 130, 7520−
7521. (b) Martin, A. D.; Easun, T. L.; Argent, S. P.; Lewis, W.; Blake,
̈
A. J.; Schroder, M. The effect of carboxylate position on the structure
of a metal organic framework derived from cyclotriveratrylene.
CrystEngComm 2017, 19, 603−607.
(16) Oshovsky, G. V.; Reinhoudt, D. N.; Verboom, W. Supra-
molecular Chemistry in Water. Angew. Chem., Int. Ed. 2007, 46,
2366−2393.
(17) (a) Perraud, O.; Dimitrov-Raytchev, P.; Martinez, A.; Dutasta,
J.-P. Resolution and Absolute Configuration Assignment of a Chiral
Hemicryptophane Molecular Cage. Chirality 2010, 22, 885−888.
(b) Payet, E.; Dimitrov-Raytchev, P.; Chatelet, B.; Guy, L.; Grass, S.;
Lacour, J.; Martinez, A.; Dutasta, J.-P. Absolute Configuration and
Enantiodifferentiation of a Hemicryptophane Incorporating an
Azaphosphatrane Moiety. Chirality 2012, 24, 1077−1081. (c) Schmitt,
A.; Chatelet, B.; Collin, S.; Dutasta, J.-P.; Martinez, A. Chiral
Discrimination of Ammonium Neurotransmitters by C3-Symmetric
Enantiopure Hemicryptophane Hosts. Chirality 2013, 25, 475−479.
(18) (a) Gautier, A.; Mulatier, J.-C.; Crassous, J.; Dutasta, J.-P.
Chiral Trialkanolamine-Based Hemicryptophanes: Synthesis and
́
Oxovanadium Complex. Org. Lett. 2005, 7, 1207−1210. (b) Bregier,
F.; Karuppannan, S.; Chambron, J.-C. A Hybrid Cavitand Made by
Capping Permethylated α-Cyclodextrin with Cyclotriveratrylene. Eur.
́
J. Org. Chem. 2012, 2012, 1920−1925. (c) Bregier, F.; Lavalle, J.;
Chambron, J.-C. Capping α-Cyclodextrin with Cyclotriveratrylene by
Triple Disulfide-Bridge Formation. Eur. J. Org. Chem. 2013, 2013,
(11) (a) Schmitt, A.; Robert, V.; Dutasta, J.-P.; Martinez, A.
Synthesis of the First Water-Soluble Hemicryptophane Host:
Selective Recognition of Choline in Aqueous Medium. Org. Lett.
2014, 16, 2374−2377. (b) Zhang, D.; Gao, G.; Guy, L.; Robert, V.;
Dutasta, J.-P.; Martinez, A. A fluorescent heteroditopic hemi-
cryptophane cage for the selective recognition of choline phosphate.
Chem. Commun. 2015, 51, 2679−2682. (c) Erieau-Peyrard, L.;
́
2666−2671. (d) Lefevre, S.; Heloin, A.; Pitrat, D.; Mulatier, J.-P.;
Vanthuyne, N.; Jean, M.; Dutasta, J.-P.; Guy, L.; Martinez, A.
Cyclotriveratrylene-BINOL-Based Host Compounds: Synthesis,
Absolute Configuration Assignment, and Recognition Properties. J.
Org. Chem. 2016, 81, 3199−3205.
(19) Potopnyk, M. A.; Jarosz, S. Nitrogen-Containing Macrocycles
Having a Carbohydrate Scaffold. Adv. Carbohydr. Chem. Biochem.
2014, 71, 227−295.
(20) Jarosz, S. Fine Chemicals with High Added Value from
Sucrose: Synthesis of Macrocyclic Receptors from “Normal” Sugar. J.
Carbohydr. Chem. 2015, 34, 365−387.
́
́
Coiffier, C.; Bordat, P.; Begue, D.; Chierici, S.; Pinet, S.; Gosse, I.;
Baraille, I.; Brown, R. Selective, direct detection of acetylcholine in
PBS solution, with self-assembled fluorescent nano-particles: experi-
ment and modelling. Phys. Chem. Chem. Phys. 2015, 17, 4168−4174.
(d) Lefevre, S.; Zhang, D.; Godart, E.; Jean, M.; Vanthuyne, N.;
E
DOI: 10.1021/acs.orglett.9b02451
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(21) Vaccari, G.; Mantovani, G. Sucrose crystallisation in: Sucrose.
Properties and Applications; Mathlouthi, M., Reiser, P., Eds.; Springer
Science+Business Media Dordrecht: 1995; pp 33−34.
(22) (a) Marra, A.; Dondoni, A. Calixarene and Calixresorcarene
Glycosides: Their Synthesis and Biological Applications. Chem. Rev.
2010, 110, 4949−4977. (b) Yang, F.; Chen, Q.; Cheng, Q.-Y.; Yan,
C.-G.; Han, B.-H. Sugar-Functionalized Water-Soluble Cyclotrivera-
trylene Derivatives: Preparation and Interaction with Fullerene. J. Org.
Chem. 2012, 77, 971−976.
(23) van Ameijde, J.; Liskamp, R. M. J. Synthesis of novel trivalent
amino acid glycoconjugates based on the cyclotriveratrylene (‘CTV’)
scaffold. Org. Biomol. Chem. 2003, 1, 2661−2669.
́
(24) Bregier, F.; Aubert, E.; Espinosa, E.; Chambron, J.-C. An
Optically-Pure Hemicryptophane as NMR and ECD Responsive
Probe for Chloroform. ChemistrySelect 2016, 1, 2389−2395.
(25) Lewandowski, B.; Jarosz, S. Chiral recognition of α-phenyl-
ethylamine by sucrose-based macrocyclic receptors. Chem. Commun.
2008, 6399−6401.
(26) (a) Potopnyk, M. A.; Lewandowski, B.; Jarosz, S. Novel
sucrose-based macrocyclic receptors for enantioselective recognition
of chiral ammonium cations. Tetrahedron: Asymmetry 2012, 23,
1474−1479. (b) Potopnyk, M. A.; Jarosz, S. Synthesis and
Complexation Properties of “Unsymmetrical” Sucrose-Based Recep-
tors. Eur. J. Org. Chem. 2013, 2013, 5117−5126.
(27) Potopnyk, M. A.; Cmoch, P.; Jarosz, S. Short Synthesis of
Diamide-Linked Sucrose Macrocycles. Org. Lett. 2012, 14, 4258−
4261.
(28) (a) Łęczycka-Wilk, K.; Dąbrowa, K.; Cmoch, P.; Jarosz, S.
Chloride-Templated Macrocyclization and Anion-Binding Properties
of C2-Symmetric Macrocyclic Ureas from Sucrose. Org. Lett. 2017, 19,
4596−4599. (b) Łęczycka-Wilk, K.; Ulatowski, F.; Cmoch, P.; Jarosz,
S. Choose-a-size” control in the synthesis of sucrose based urea and
thiourea macrocycles. Org. Biomol. Chem. 2018, 16, 6063−6069.
(29) Brotin, T.; Devic, T.; Lesage, A.; Emsley, L.; Collet, A.
Synthesis of Deuterium-Labeled Cryptophane-A and Investigation of
Xe@Cryptophane Complexation Dynamics by 1D-EXSY NMR
Experiments. Chem. - Eur. J. 2001, 7, 1561−1573.
(30) (a) Pescitelli, G.; Bruhn, T. Good Computational Practice in
the Assignment of Absolute Configurations by TDDFT Calculations
of ECD Spectra. Chirality 2016, 28, 466−474. (b) Berova, N.;
Polavarapu, P. L.; Nakanishi, K.; Woody, R. W. Comprehensive
Chiroptical Spectroscopy, Vols. 1 and 2; Wiley: 2012.
(31) Long, A.; Colomban, C.; Jean, M.; Albalat, M.; Vanthuyne, N.;
́
Giorgi, M.; Di Bari, L.; Gorecki, M.; Dutasta, J.-P.; Martinez, A.
Enantiopure C1-Cyklotriveratrylene with a Reversed Spatial Arrange-
ment of the Substituents. Org. Lett. 2019, 21, 160−165.
(32) Canceill, J.; Collet, A.; Gabard, J.; Gottarelli, G.; Spada, G. P.
Exciton Approach to the Optical Activity of C3-Cyclotriveratrylene
Derivatives. J. Am. Chem. Soc. 1985, 107, 1299−1308.
F
DOI: 10.1021/acs.orglett.9b02451
Org. Lett. XXXX, XXX, XXX−XXX