An azobenzene container showing a definite folding - Synthesis and structural investigation

Article abstract of DOI:10.3762/bjoc.15.156

The combination of photo-switchable units with macrocycles is a very interesting field in supramolecular chemistry. Here, we present the synthesis of a foldable container consisting of two different types of Lissoclinum macrocyclic peptides which are conn

Full text of DOI:10.3762/bjoc.15.156

An azobenzene container showing a definite folding –
synthesis and structural investigation
Abdulselam Adam, Saber Mehrparvar and Gebhard Haberhauer*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 1534–1544.
Institut für Organische Chemie, Universität Duisburg-Essen,
Universitätsstr. 7, D-45117 Essen, Germany
doi:10.3762/bjoc.15.156
Received: 15 April 2019
Accepted: 25 June 2019
Published: 10 July 2019
Email:
Gebhard Haberhauer* - gebhard.haberhauer@uni-due.de
* Corresponding author
This article is part of the thematic issue "Novel macrocycles – and old
ones doing new tricks".
Keywords:
azobenzene; macrocycles; molecular switch
Guest Editor: W. Jiang
© 2019 Adam et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
The combination of photo-switchable units with macrocycles is a very interesting field in supramolecular chemistry. Here, we
present the synthesis of a foldable container consisting of two different types of Lissoclinum macrocyclic peptides which are
connected via two azobenzene units. The container is controllable by light: irradiation with UV light causes a switching process to
the compact cis,cis-isomer, whereas by the use of visible light the stretched trans,trans-isomer is formed. By means of quantum
chemical calculations and CD spectroscopy we could show that the trans→cis isomerization is spatially directed; that means that
one of the two different macrocycles performs a definite clockwise rotation to the other, caused by irradiation with UV light. For
the cis→trans isomerization counterclockwise rotations are found. Furthermore, quantum chemical calculations reveal that the
energy of the cis,cis-isomer is only slightly higher than the energy of the cis,trans-isomer. This effect can be explained by the high
dispersion energy in the compact cis,cis-isomer.
Introduction
In supramolecular chemistry rigid scaffolds are required to type and size of the macrocyclic platform, e.g., if all of the
arrange different recognition units in predefined distances and amino acid side chains are of the same configuration, they are
spatial orientation to each other [1]. One example for such rigid presented on one face of the macrocycle in a convergent
systems are macrocycles which stem from Lissoclinum cyclo- manner. The artificial Lissoclinum cyclopeptide platforms fea-
peptide alkaloids (Figure 1) [2,3]. Here, the required recogni- ture C2, C3 and C4 symmetry [3]. So far, a series of receptors
tion units can be introduced via the amino acid side chains or based on these macrocycles were synthesized. They have been
via the side chains of the azole rings. The orientation and the designed for the selective recognition of sulfate ions [4-6], di-
distance between the recognition units are determined by the and triphosphate ions [7], for sensing of pyrophosphate ions in
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Figure 1: Some examples for artificial C2- and C3-symmetric platforms based on Lissoclinum cyclopeptide alkaloids.
aqueous solutions [8], as receptors for phenols [9], α-chiral pri- tion of the distance between the two isopropyl groups. As
mary organoammonium ions [10], and biomolecules [11-17]. further example the chiral foldable container 5 should be
Furthermore, modified Lissoclinum cyclopeptides were used for mentioned [49]. Here, two imidazole-containing macrocycles
the construction of novel tubular and cage structures [18,19], as are linked to each other by two azobenzene units (Figure 2). Ir-
prototypes for mimicking multiple loops of proteins [20] and radiation with UV light causes two consecutive trans→cis
for homochiral supramolecular polymerization [21,22]. Beside isomerization’s resulting in a stepwise decrease of the distance
the usage of the side chains of the amino acids and the azole of the two macrocycles. Accordingly, the distance between the
rings for molecular recognition, the functional groups of the recognition units at the upper and the lower macrocycle
scaffolds of these cyclopeptides have also been applied as re- decreases stepwise as well.
ceptors for Y-shaped anions [23] and as ligands for copper(II)
complexes [24,25].
In the chiral container 5 two identical macrocycles are
connected to each other. A further development would be a
Of special interest is the design of artificial Lissoclinum foldable container featuring two different macrocycles which
cyclopeptides which can be switched by the incorporation of a allows to distinguish between the upper and the lower part of
suitable switching unit into the scaffold. A switching process the container. Here, we present the synthesis and the structural
would allow to vary the orientation and the distance between investigation of a switchable chiral container in which two dif-
the recognition units. Examples for such switching units are ferent C2-symmetric artificial Lissoclinum cyclopeptides are
photochromic molecules which can be reversibly changed be- connected by two azobenzene bridges. A light-induced
tween two isomers of different structures [26-29]. One promi- switching process leads to a spatially directed collapse of the
nent switching unit is azobenzene and its derivatives [30-41]. container which can be detected by an increase of the diffusion
The trans-isomer features a stretched and the cis-isomer has a coefficient of the molecule.
compact geometry. In general, the trans→cis isomerization is
triggered by UV light whereas the cis→trans back relaxation
Results and Discussion
takes place by visible light or heat [30,42]. Due to the high re- Synthesis of the chiral foldable container
versibility, the simple synthesis and the high photostability For the design of the chiral switchable container we intended to
azobenzene derivatives are the most commonly used switching use the imidazole-containing peptides 2a (R = R’ = iPr) and 3a
units. A further advantage of the use of azobenzene as (R = R’ = iPr) as macrocycles (see Figure 1 and Scheme 1).
switching unit is the fact that it is possible to control the confor- Both feature two imidazole units which should be used to at-
mation of the cis or the trans-isomers by chiral bridges [43-48].
tach the azobenzene groups. Additionally, platform 2a has two
valine units, whereas platform 3a possesses two oxazole rings.
Up to now two artificial Lissoclinum cyclopeptides, which fea- Overall, both macrocycles feature four amino acid side chains
ture an azobenzene moiety to change the distance between the (isopropyl groups), whereby all of them are of the same config-
amino acid side chains, are described in the literature [49,50]. uration (S). Therefore, they are presented on one face of the
One example is the platform 4, which consists of two imida- macrocycle in a convergent manner.
zole building blocks connected by two azobenzene units
(Figure 2) [50]. Irradiation of the platform 4 with UV light Platform 3a was synthesized in a few steps according to a
results in a trans→cis isomerization accompanied by a reduc- known procedure (Scheme 1) [51]. Therefore, the imidazole-
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Figure 2: a) Principle of a chiral foldable platform and container based on Lissoclinum cyclopeptide alkaloids. b) Switchable molecular platform 4 and
switchable molecular container 5.
Scheme 1: Synthesis of the chiral foldable container 10. Reaction conditions: i) FDPP, iPr2NEt, CH3CN, 90%; ii) MeOH, dioxane, NaOH, quant.;
iii) EtOAc, HCl, quant.; iv) FDPP, iPr2NEt, CH3CN, 50%; v) MeOH, Pd(OH)2/C, H2, 95%; vi) 3a, K2CO3, CH3CN, Δ, 15%.
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containing acid 6 was reacted with the free amine 7 using penta- of the density functionals B3LYP and B3LYP-D3 were per-
fluorophenyl diphenylphosphinate (FDPP) as coupling reagent formed by using the basis set def2-TZVP [60,61]. The thus ob-
resulting in the formation of amide 8. After saponification of tained data are listed in Table 1. The calculated structures are
the methyl ester and removal of the Boc protective group, the shown in Figure 3 and Figures S1 and S2 in Supporting Infor-
resulting amino acid was cyclodimerized to the benzyl-pro- mation File 1. For comparison, the data for azobenzene were
tected macrocycle. The yield for the cyclization amounts to also calculated using the same level of theory and are listed in
about 50%. The last step was the removal of the benzyl group Table 1.
by hydrogenolysis to yield the desired macrocycle 3a. The
cyclopeptide 2a [52] is commercially available.
Table 1: Relative energies [kcal/mol] of the isomers of 10 and azoben-
zene calculated using different methods.
Initially, we tried to synthesize the chiral foldable container 10
compound
ΔEa
ΔEb
starting from the macrocycles 2a and 3a in a stepwise manner.
That means, we intended to react in a first step one macrocycle
with two azobenzene units having each one reactive and one
protected group. In a second step we wanted to transform the
protected groups at the azobenzene units into reactive groups.
The latter should react in a third step with the other macrocycle.
However, although we varied the reaction sequence regarding
the used macrocycles, none of these reaction pathways led to
the desired molecule. Therefore, we changed our strategy and
we tried to synthesize the chiral foldable container 10 in a one
trans,trans-10
cis,trans-10
cis,cis-10
trans-azobenzene
cis-azobenzene
0.0
20.0
34.0
0.0
0.0
8.3
10.2
0.0
15.1
12.6
aB3LYP/def2-TZVP//B3LYP/6-31G*. bB3LYP-D3/def2-TZVP//B3LYP-
D3/6-31G*.
pot reaction. For this purpose, the platforms 2a and 3a and the A comparison of the data for azobenzene and the chiral
dibromide 9 were dissolved in acetonitrile in the ratio 1:1:2.2. container 10 calculated by means of B3LYP/def2-TZVP shows
To this solution potassium carbonate as base was added and the that the trans→cis isomerization of trans,trans-10 is associated
whole mixture was refluxed for one day. Fortunately, the with an energy increase of 20 kcal/mol (Table 1). The energy
desired container was formed in a yield of 15%, which is aston- difference between trans-azobenzene and cis-azobenzene calcu-
ishingly good considering the multiple reaction paths. As by- lated at the same level of theory amounts to only 15.1 kcal/mol.
products the containers consisting of each two identical macro- That means that the trans→cis isomerization of trans,trans-10
cycles 2a and 3a, respectively, are formed. These containers is accompanied by an introduction of additional strain energy of
could not be separated from each other. The isolation of the about 5 kcal/mol. For the transition from trans,trans-10 to
desired container was achieved by column chromatography fol- cis,cis-10 an energy of 34.0 kcal/mol is required. This is ca.
lowed by HPLC. It is noteworthy that the synthesis of this 4 kcal/mol more than twice the energy of the trans→cis isomer-
container showing two different Lissoclinum cyclopeptides only ization of azobenzene. Accordingly, the cis,cis-10 exhibits an
took a couple of steps starting from an imidazole and an additional strain energy of about 4 kcal/mol compared to
oxazole building block, an azobenzene unit as well as commer- trans,trans-10.
cially available compounds.
A completely different picture emerges when the dispersion
correction D3 is taken into account (B3LYP-D3/def2-TZVP;
Table 1). The trans→cis isomerization of trans,trans-10 to
Investigation of the structure and the
switching process
To investigate the structures of the foldable container 10 in the cis,trans-10 is energetically favored (8.3 kcal/mol) compared to
gas phase, the geometric parameters of the trans,trans-, the transition from trans-azobenzene to cis-azobenzene
cis,trans- and cis,cis-isomers were fully optimized by means of (12.6 kcal/mol). The energy input for the switching process be-
the DFT potentials B3LYP [53-55] and B3LYP-D3 [56,57]. tween cis,trans-10 to cis,cis-10 amounts to only 1.9 kcal/mol.
The latter includes an additional dispersion correction and de- The reason for that is the high gain of attractive dispersion
scribes dispersion interactions more accurately for larger atomic interactions due to the compact structure of the cis,cis-isomer.
distances. As basis set 6-31G* [58,59] was applied. In the case Therefore, we expected that the switching process from
of the cis,trans- and cis,cis-isomers we tried to calculate all cis,trans-10 to cis,cis-10 is more easily realizable by an extern
possible conformations [cis,trans-(M), cis,trans-(P), cis,cis- light stimulus than the transition from trans,trans-10 to
(M,M), cis,cis-(M,P) and cis,cis-(P,P)]. However, it turned out cis,trans-10. This would be very much in line with our idea to
that the P conformers represent no minima on the potential design an chiral container which can be switched between two
energy surface. Furthermore, single point calculations by means main states (trans,trans and cis,cis).
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Figure 3: Molecular structures of trans,trans-10 (left), cis,trans-10 (middle) and cis,cis-10 (right) calculated by means of B3LYP/6-31G*. All hydrogen
atoms are omitted for the sake of clarity.
The structures of the three isomers of container 10 calculated by tion. Irradiation of the solution with UV light of the length
means of B3LYP/6-31G* are depicted in Figure 3. As expected, λ = 365 nm leads to a strong decrease of the absorption band at
the connection of the two macrocycles 2a and 3a via two trans- 323 nm and to a hypsochromic shift of the n→π* transition
azobenzenes (trans,trans-10) results in a longer distance be- band to ca. 430 nm (Figure 4). These changes are typical for the
tween the macrocycles compared to a connection via two cis- transition of trans-azobenzene units to the corresponding cis-
azobenzenes (cis,cis-10). The distance between the centers of isomers. A back-isomerization could be achieved by irradiation
the two macrocycles in the trans,trans-isomer amounts to of the solution with light of the wavelength λ = 405 nm. The
14.1 Å. For cis,cis-10 a decrease of this distance to 11.3 Å is switching process could be repeated several times without a sig-
calculated. The corresponding value for the cis,trans isomer nificant change of the spectra.
amounts to 11.8 Å, which is only slightly larger compared to
the data of cis,cis-10. Therefore, according to the calculations In order to determine the ratio of the three isomers of the
the chiral container 10 should show the desired change caused container 10 in dependence on the used light, the whole process
by extern stimulation.
was investigated by using HPLC and NMR spectroscopy. In
both cases methanol was used as solvent. The switching pro-
It is notable that the switching process from trans,trans-10 to cesses caused by light were carried out with LED lamps and the
cis,cis-10 is accompanied by a clockwise rotation of the two solution was irradiated until the photostationary states were
macrocycles towards each other. This could be explained as reached. In Figure 5 the 1H NMR spectra of the container 10 are
follows: In trans,trans-10 the two azobenzene bridges are not depicted. After the synthesis, the foldable container is predomi-
perpendicularly arranged to the macrocycles, but they show a nantly present as trans,trans-isomer (Figure 5a). The other
left-hand twist (Figure 3 and Figure S1 in Supporting Informa- signals in the spectrum stem from the C1-symmetric cis,trans-
tion File 1). The trans→cis isomerization enhances this left- isomer, which can easily be recognized by the large number of
hand twist leading to a clockwise rotation of the two macro- signals. The ratio trans,trans/cis,trans/cis,cis was determined to
cycles towards each other.
be 68:31:<1.
To prove the switching process experimentally, the UV spectra Irradiation with light of the wavelength λ = 365 nm results in
of the container 10 in acetonitrile as solvent were recorded the formation of the cis,trans- and cis,cis-isomers. Accordingly,
(Figure 4). After the synthesis, the UV spectrum of the a trans,trans/cis,trans/cis,cis ratio of 12:39:49 can be found
container shows an intensive band at 323 nm and a weak band (Figure 5b). If this mixture is now irradiated with light of the
at ca. 450 nm. The absorption at 323 nm corresponds to the wavelength λ = 405 nm the trans,trans-isomer is formed back
π→π* transition, the second one is caused by the n→π* transi- and the trans,trans/cis,trans/cis,cis ratio changes to 77:22:<1
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Figure 4: UV spectra of the foldable container 10 in acetonitrile after synthesis (blue), after irradiation with light of the wavelength λ = 365 nm (red),
after irradiation with light of the wavelength λ = 405 nm (black) and after irradiation with light of the wavelength λ = 365 nm (green).
Figure 5: Section from the 1H NMR spectra of the foldable container 10 in MeOD at 600 MHz: a) after synthesis, b) after irradiation with light of the
wavelength λ = 365 nm, c) after irradiation with light of the wavelength λ = 405 nm and d) after irradiation with light of the wavelength λ = 365 nm. The
protons of the isomers trans,trans-10 (blue squares), cis,trans-10 (green triangles) and cis,cis-10 (red circles) are marked.
(Figure 5c). The switching process can be repeated without a (68:31:<1). After irradiation with light of the wavelength
significant change of the spectrum (Figure 5d; trans,trans/ λ = 365 nm a trans,trans/cis,trans/cis,cis ratio of 4:26:70 is ob-
cis,trans/cis,cis ratio = 11:39:50).
served, which is distinctly higher than that found using
1H NMR spectroscopy (12:39:49). Also the back-isomerization
The HPLC spectra of the investigation of the switching process caused by light of the wavelength λ = 405 nm results in an
are shown in the Supporting Information File 1 (Figures higher amount of the trans,trans-isomer (trans,trans/cis,trans/
S3–S6). A comparison of the corresponding 1H NMR spectra cis,cis = 80:19:1). It is also possible to get a mixture having the
shows that the extent of the switching process is dependent on cis,trans-isomer as main component, if the solution is exposed
the concentration of the azo compound. The more diluted the to light of the wavelength λ = 530 nm (trans,trans/cis,trans/
solution, the larger are the changes caused by the LED lamps. cis,cis = 8:60:32).
This effect is already known for this kind of switches [49,50].
The trans,trans/cis,trans/cis,cis ratio of the solution after syn- The use of preparative HPLC allows the isolation of the single
thesis amounts to 63:35:2 and resemble the 1H NMR data isomers and the investigation of the separated compounds.
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Therefore, the single HPLC peaks were collected and measured azobenzene derivatives is dominated by only one transition
within a few minutes by CD spectroscopy. The purity of the (n→π*). Accordingly, the conformation (M or P) of the cis-
separated isomers was tested as follows: after collection of the azobenzene moiety can directly be identified from the sign of
single HPLC peaks and a waiting time of about 20 min, HPLC the Cotton effect at 450 nm. Previous studies have demon-
chromatograms of the single fractions were recorded. These strated that the cis-(M) isomer shows a positive and the cis-(P)
chromatograms show a purity of >93% for each isomer isomer has a negative Cotton effect in this region [43,49]. If this
(Figure 6).
is taken into account, it becomes obvious that the cis,cis-isomer
adopts the M,M conformation. This is in line with the DFT
The CD spectra of the single isomers of the container 10 are calculations finding only the cis,cis-(M,M) isomer as minimum
shown in Figure 7. It should be mentioned that the area around on the energy potential surface. The spectrum of cis,trans-10
450 nm of the CD spectra of simple alkyl-substituted cis- allows the conclusion that the cis-azobenzene unit is present in
Figure 6: HPLC spectra (ReproSil Phenyl, 5 μm, 250 × 8 mm; methanol) of trans,trans-10 (blue), cis,trans-10 (green) and cis,cis-10 (red) 20 min after
isolation by means of HPLC.
Figure 7: CD spectra of trans,trans-10 (blue), cis,trans-10 (green), and cis,cis-10 (red) in methanol (c = 3.0 × 10−5 M).
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its M conformation. For the P conformation we would expect a peptides which are connected via two azobenzene units. The
negative Cotton in the area around 450 nm. That means the synthesis of this container was achieved by a one pot reaction of
chiral information is transferred from both macrocycles to the the two imidazole-containing macrocycles and the azobenzene
cis-azobenzene units in cis,trans-(M)-10 and cis,cis-(M,M)-10 bridges having two reactive bromides. The desired container
and the two different macrocycles perform a definite clockwise could be isolated in a fair yield taking the multiple reaction
rotation to the other caused by irradiation with UV light and a pathways into account. Subsequent investigations by means of
counterclockwise rotation when the compound is exposed to quantum chemical calculations, UV, CD and NMR spectrosco-
visible light.
py revealed that the container can be switched using UV light
from the trans,trans-isomer into the cis,cis-isomer. Irradiation
The spatial change of the container 10 caused by the switching with visible light results in the back-isomerization. The
process could have an impact on the size of the diffusion coeffi- switching process is spatially directed, accompanied by a
cient of the compound. To examine this, DOSY spectra of the change in the diffusion coefficient and in the distance between
container 10 after synthesis and after irradiation with light of the centers of the two macrocycles: In the elongated
the wavelength λ = 365 nm were recorded (Figure 8). Please trans,trans-isomer this distance shows a value of 14.1 Å, in the
note, that a change in the geometry of a switch need not result more compact cis,cis-isomer the distance amounts to 11.3 Å.
in a change of the size of the diffusion coefficient. For example, The replace of the isopropyl groups by recognition units and the
neither for the switchable platform 5 nor for the foldable enlargement of the two linkers, which makes a shielding of a
container 6 a significant change of the diffusion coefficients guest from the environment possible, should lead to containers
caused by the switching process could be detected in the DOSY which are due to their foldable feature promising candidates for
spectra of the compounds. This can be explained as follows: applications in supramolecular chemistry.
The DOSY NMR experiment measures the average dimension
of the structures of the isomers which, summed up over all Experimental
directions, could be very comparable. However, a comparison General remarks: All chemicals were reagent grade and were
of the DOSY spectra of trans,trans-10 and cis,cis-10 shows that used as purchased. Reactions were monitored by TLC analysis
the diffusion coefficient of the elongated trans,trans-10 is with silica gel 60 F254 thin-layer plates. Flash chromatography
indeed larger than that of the more compact cis,cis-isomer was carried out on silica gel 60 (230–400 mesh). 1H and
(Figure 8).
13C NMR spectra were measured with an Avance HD 600 spec-
trometer. All chemical shifts (δ) are given in ppm. The spectra
were referenced to the peak for the protium impurity in the
Conclusion
In conclusion, we were able to synthesize a foldable container deuterated solvents indicated in brackets in the analytical data.
consisting of two different types of Lissoclinum macrocyclic HRMS spectra were recorded with a Bruker BioTOF III Instru-
Figure 8: DOSY NMR spectra (500 MHz in MeOD at 25 °C) of the foldable container 10 after synthesis (left) and after irradiation with light of the
wavelength λ = 365 nm (right).
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ment. UV–vis absorption spectra were obtained with Jasco 1592, 1506, 1498, 1458, 1188, 1110, 761, 715 cm−1; UV–vis
J-815 and V-550 spectrophotometers. CD absorption spectra (CH3CN) λmax (log ε): 202 (4.69), 229 (4.69), 328 (4.50),
were recorded with a Jasco J-815 spectrophotometer. The IR 445 nm (2.99); HRMS (ESI–TOF) m/z: [M + H]+ calcd for
absorption spectrum was recorded with a Varian 3100 FTIR C92H115N22O10, 1687.9161; found, 1687.9103; [M + Na]+
spectrophotometer. The macrocycle 3a was synthesized accord- calcd for C92H114N22O10Na, 1709.8980; found, 1709.8929.
ing to a known procedure [51]. The macrocycle 2a was pur-
chased from Squarix GmbH.
Calculations. All calculations were performed by using the
program package Gaussian 16 [62]. The geometries of the mol-
Chiral container trans,trans-10: To a solution of macrocycle ecules were fully optimized in the gas phase by using the DFT
3a (128 mg, 0.178 mmol), macrocycle 2a (99 mg, 0.178 mmol), potentials B3LYP [53-55] and B3LYP-D3 [56,57] as well as
and azobenzene 9 (144 mg, 0.391 mmol) in acetonitrile the 6-31G* [58,59] basis set. For all calculations, the default
(225 mL), potassium carbonate (491 mg, 3.554 mmol) was thresholds implemented in Gaussian 16 were used. For all sta-
added and the mixture was refluxed at 85 °C for 25 h under an tionary points, no symmetry restriction was applied. The opti-
argon atmosphere. After cooling to room temperature, the sol- mized geometries of all structures were characterized as minima
vent was evaporated to dryness, the residue was dissolved in by subsequent frequency calculations. Furthermore, the ener-
DCM and washed with water. The aqueous layer was saturated gies of the molecules were calculated using the DFT potentials
with NaCl and then repeatedly extracted with DCM. The B3LYP [53-55] and B3LYP-D3 [56,57] as well as the def2-
organic layers were combined, dried over MgSO4 and concen- TZVP [60,61] basis set.
trated in vacuo. Afterwards, the residue was purified by flash
column chromatography with silica gel (DCM/EtOAc/MeOH
75:25:5) and trans,trans-10 was obtained as an orange solid
Supporting Information
(47 mg, 28 μmol, 15%). Mp >250 °C; 1H NMR (600 MHz,
Supporting Information File 1
MeOD) δ 7.38 (d, 3JH,H = 8.4 Hz, 4H, CarH), 7.12 (d, 3JH,H =
8.4 Hz, 4H, CarH), 6.96 (d, 3JH,H = 8.4 Hz, 4H, CarH), 6.69 (d,
3JH,H = 8.4 Hz, 4H, CarH), 5.72 (d, 2JH,H = 16.9 Hz, 2H,
CH2Car), 5.51 (d, 2JH,H = 16.6 Hz, 2H, CH2Car), 5.24 (d,
3JH,H = 9.3 Hz, 2H, NHCH), 5.21 (d, 2JH,H = 16.9 Hz, 2H,
CH2Car), 5.06 (d, 2JH,H = 16.6 Hz, 2H, CH2Car), 5.03 (d,
3JH,H = 8.0 Hz, 2H, NHCH), 4.81 (d, 3JH,H = 8.7 Hz, 2H,
NHCH), 4.25 (d, 3JH,H = 9.6 Hz, 2H, NHCH), 2.61–2.53 (m,
2H, CH(CH3)2), 2.48 (s, 6H, CazolCH3), 2.44–2.35 (m, 4H,
CH(CH3)2), 2.28 (s, 6H, CazolCH3), 2.27 (s, 6H, CazolCH3),
2.24–2.19 (m, 2H, CH(CH3)2), 1.20 (d, 3JH,H = 6.7 Hz, 6H,
CH(CH3)2), 1.16 (d, 3JH,H = 6.5 Hz, 6H, CH(CH3)2), 1.15 (d,
3JH,H = 6.5 Hz, 6H, CH(CH3)2), 1.10 (d, 3JH,H = 6.8 Hz, 6H,
CH(CH3)2), 1.09 (d, 3JH,H = 6.7 Hz, 6H, CH(CH3)2), 1.01 (d,
3JH,H = 6.7 Hz, 6H, CH(CH3)2), 0.98 (d, 3JH,H = 6.7 Hz, 6H,
CH(CH3)2), 0.93 (d, 3JH,H = 6.8 Hz, 6 H, CH(CH3)2) ppm;
13C NMR (151 MHz, MeOD) δ 174.0 (q, CO), 165.8 (q, CO),
165.3 (q, CO), 164.5 (q, CO), 162.9 (q, Car), 154.9 (q, Car),
152.8 (q, Car), 152.2 (q, Car), 148.6 (q, Car), 148.1 (q, Car),
140.8 (q, Car), 140.6 (q, Car), 135.5 (q, Car), 135.1 (q, Car),
131.4 (q, Car), 131.0 (q, Car), 129.7 (q, Car), 128.3 (t, Car),
128.1 (t, Car), 124.5 (t, Car), 124.2 (t, Car), 62.4 (t, CHNH), 54.6
(t, CHNH), 52.4 (t, CHNH), 51.0 (t, CHNH), 48.2 (s, CH2Car),
48.1 (s, CH2Car), 35.9 (t, CH(CH3)2), 34.7 (t, CH(CH3)2), 33.1
(t, CH(CH3)2), 31.5 (t, CH(CH3)2), 20.3 (p, CH(CH3)2), 20.0
(p, CH(CH3)2), 19.8 (p, CH(CH3)2), 19.7 (p, CH(CH3)2), 19.6
(p, CH(CH3)2), 19.5 (p, CH(CH3)2),19.5 (p, CH(CH3)2), 19.2
(p, CH(CH3)2), 11.6 (p, CqCH3), 10.9 (p, CqCH3), 10.6 (p,
Molecular structures, HPLC spectra of the foldable
container, cartesian coordinates and absolute energies for
all calculated compounds, as well as the NMR spectra of
the new chiral container.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-156-S1.pdf]
Acknowledgements
This work was generously supported by the Professor Werdel-
mann-Stiftung (T167/23664/2013).
ORCID® iDs
Abdulselam Adam - https://orcid.org/0000-0003-3588-5737
Gebhard Haberhauer - https://orcid.org/0000-0002-5427-7510
Preprint
A non-peer-reviewed version of this article has been previously published
as a preprint doi:10.3762/bxiv.2019.9.v1
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