Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

Article abstract of DOI:10.3762/bjoc.15.177

A series of hetero [4]-, [5]- and [6]rotaxanes containing both cucurbit[6]uril (CB[6]) and γ-cyclodextrin (γ-CD) as the macrocyclic components have been synthesized via a threading-followed-by-stoppering approach. Due to the orthogonal binding of CB[6] to ammonium and γ-CD to biphenylene/tetra(ethylene glycol), the [n]rotaxanes display a specific sequence of the interlocked macrocycles. In addition, despite of the asymmetry of γ-CD with respect to the orthogonal plane of the axle, only one stereoisomer of the [6]rotaxane was obtained.

Full text of DOI:10.3762/bjoc.15.177

Synthesis of a [6]rotaxane with singly threaded
γ-cyclodextrins as a single stereoisomer
Jason Yin Hei Man and Ho Yu Au-Yeung*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 1829–1837.
Department of Chemistry, The University of Hong Kong, Pokfulam
Road, Hong Kong, P. R. China
doi:10.3762/bjoc.15.177
Received: 15 May 2019
Accepted: 15 July 2019
Published: 01 August 2019
Email:
Ho Yu Au-Yeung* - hoyuay@hku.hk
* Corresponding author
This article is part of the thematic issue "Novel macrocycles – and old
ones doing new tricks".
Keywords:
cucurbit[6]uril; cyclodextrin; macrocycles; mechanostereoisomer;
rotaxane
Guest Editor: W. Jiang
© 2019 Man and Au-Yeung; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
A series of hetero [4]-, [5]- and [6]rotaxanes containing both cucurbit[6]uril (CB[6]) and γ-cyclodextrin (γ-CD) as the macrocyclic
components have been synthesized via a threading-followed-by-stoppering approach. Due to the orthogonal binding of CB[6] to
ammonium and γ-CD to biphenylene/tetra(ethylene glycol), the [n]rotaxanes display a specific sequence of the interlocked macro-
cycles. In addition, despite of the asymmetry of γ-CD with respect to the orthogonal plane of the axle, only one stereoisomer of the
[6]rotaxane was obtained.
Introduction
Cyclodextrins (CDs) are macrocycles composed of glucoses cavity size that could accommodate up to two aromatic guests
linked via α-1,4-glycosidic bonds. CDs of six (α-CD), seven to form 1:2 host–guest complexes, in contrast to the usual for-
(β-CD) and eight (γ-CD) glucose units are important molecular mation of 1:1 complex by α-CD and β-CD [10,11]. In addition
hosts that show binding to a wide range of compounds and find to host–guest chemistry, the favourable binding of CDs to
applications in different fields including food and pharmaceuti- common organic scaffolds has also made CDs popular building
cal industries [1-5]. CDs are of cone shape with two different blocks for the construction of complex molecular topology such
openings: a narrower primary face with primary hydroxy as rotaxanes and catenanes [12-15]. For example, by making
groups and a wider secondary face with secondary hydroxy use of hydrophobic-driven binding of simple alkyl groups in
groups [6,7]. With the hydrophobic cavity and the hydrophilic water to α-CD, Ogino has reported one first example of a
hydroxy groups, CDs efficiently form host–guest complexes rotaxane assembly featuring an alkyldiamine threaded through
with different hydrophobic guests in aqueous medium [8,9]. an α-CD [16]. The corresponding rotaxane with a β-CD was ob-
Among the common CDs, γ-CD possesses a relatively large tained in lower yield, probably due to a weaker binding of the
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alkyl group to β-CD as a result of a size mismatch [17]. For interlocking of the macrocycle is ensured to result in a good
β-CD with a larger cavity, interlocked molecules derived from efficiency of mechanical bond formation. The synthesis of 1
aromatic units such as biphenyl, stilbene, cyanine and azoben- and 2 is depicted in Scheme 1.
zene have also been reported [18-24]. High order oligorotax-
anes with a multiple number of α- or β-CDs threaded through
polymer chains have also been prepared [25-28]. The inter-
locked CDs have been shown to provide an interesting insu-
lating effect to π-conjugated polymers [29-31].
On the other hand, γ-CD is relatively less employed in the syn-
thesis of mechanically interlocked molecules despite of its
ability to form interesting 1:2 inclusion complexes, and there
are only few examples of rotaxane and catenane featuring γ-CD
as an interlocked macrocycle [32-36]. By adopting a stepwise
stoppering approach, Anderson and co-workers have synthe-
sized a [3]rotaxane consisting of two different axles, derived
from a stilbene and a cyanine, threaded through one γ-CD [33].
Inouye has also reported a [3]rotaxane with two pyrene-derived
axles threaded through one γ-CD [34]. More recently, Yang and
co-workers have described a rotaxane-based host that detects
tryptophan which binds to the γ-CD cavity of the rotaxane [35].
As part of our program in the synthesis and application of com-
plex, multicomponent interlocked molecules [37-39], we are
interested in exploiting the binding capability of γ-CD in the
construction of high order [n]rotaxanes and [n]catenanes.
Here, we report our work on the synthesis of multiring,
hetero[n]rotaxane containing γ-CD and cucurbit[6]uril (CB[6])
as the macrocyclic components in an aqueous medium. Because
of the orthogonal binding of γ-CD to biphenylene and
tetra(ethylene glycol) and CB[6] to ammonium, [n]rotaxanes of
Scheme 1: Synthesis of the axle and stopper building blocks 1 and 2.
only a specific sequence of the interlocked macrocycles were
obtained despite of the possibility of other sequence isomers. In
addition, the three γ-CDs in the [6]rotaxane were found to adopt To synthesize hetero[n]rotaxanes containing both γ-CD and
only one orientation, possibly due to inter-ring interactions with CB[6], a 1:1 mixture of the anthracene stopper 2 and CB[6] in
the CB[6], to give the [6]rotaxane as one single stereoisomer. 50 mM HCl was first heated at 100 °C for 5 minutes in a micro-
Considering the ability of γ-CD to form stable 1:2 inclusion wave reactor to facilitate the dissolution of the CB[6]
complexes, these singly threaded [n]rotaxanes could serve as an (Scheme 2). The solution was then added to a solution mixture
entry point to other high order interlocked structures by further of the biphenylene building block 1 and γ-CD at different ratios,
interlocking at the γ-CD.
and the mixture was heated at 60 °C overnight. The products
were analyzed by LC–MS. Contrary to most reports on the
inclusion of simple aromatic or poly(ethylene glycol) in γ-CD
Results and Discussion
Building block design and rotaxane synthesis where a 2:1 binding stoichiometry was observed, LC–MS anal-
To encourage complex formation with γ-CD, axle 1 was de- ysis of the reaction mixture containing a 2:1 molar ratio of
signed with a biphenylene core to bind to the macrocycle 1/γ-CD stoppered by 2 showed only the [3]rotaxane 3R (93%,
through hydrophobic effect. The axle is terminated by m/z = 798.0, 4+; 1063.8, 3+) and a small amount of the
2-aminoethyl azide for CB[6]-mediated azide–alkyne cycload- [4]rotaxane 4R (7%, m/z = 1122.0, 4+) with no doubly threaded
dtion (CBAAC) with the anthracene-derived propagylamine product observed. The low efficiency of γ-CD interlocking may
stopper 2. In CBAAC, the strong ammonium–CB[6] binding be due to the weak γ-CD binding under the reaction conditions,
places the alkyne and azide in a close proximity inside the especially when heat was applied for the CBAAC. Electrostatic
CB[6] cavity and facilitates the cycloaddition [40-42]. Since repulsion between the positively charged ammoniums under the
CB[6] binding is required for the covalent bond formation, acidic reaction conditions may also weaken the formation of the
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Scheme 2: Synthesis of [n]rotaxanes 3R to 6R. Note that the position and orientation of the γ-CD are arbitrary.
2:1 complex. To promote γ-CD inclusion in the final rotaxane two or more isomeric forms of 5R which are non-interconvert-
product, a larger amount of γ-CD was used. When 5 equiv of ible on the chromatographic time scale. The [n]rotaxanes were
γ-CD was used, the yield of 4R increases significantly to 41% all purified by preparative HPLC and characterized by
at the expense of 3R. Interestingly, a small amount of the 1H NMR, 13C{1H} NMR, HRESIMS, and tandem MS. The
[5]rotaxane 5R (12%, m/z = 1446.7; 4+) was also observed. HRESIMS spectra of 3R, 4R, 5R and 6R all show an isotopic
Further increasing the amount of γ-CD gave more of the higher pattern that is consistent with the respective molecular formula
order 5R and even the [6]rotaxane 6R (m/z = 1416.7, 6+; (Figures S20–S23 in Supporting Information File 1). In the MS/
1770.6, 4+), with the latter obtained in 26% yield when MS spectra, fragments corresponding to the loss of the γ-CD
50 equiv of γ-CD was used (Figure 1). Of note, while 3R, 4R and the anthracene stoppers were observed, suggesting the
and 6R appear as a single peak in the LC chromatogram, two breaking of the glycosidic bonds of the γ-CD and the
closely eluted peaks with mass signals consistent with the anthracene–CH2(NRH2)+ bond as the major fragmentation
[5]rotaxane were observed for 5R, suggesting the existence of pathways (Figures S24–S27 in Supporting Information File 1).
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NMR structures of the hetero[n]rotaxanes
Structures of the hetero[n]rotaxanes were further characterized
by 1H NMR in D2O. Interestingly, the structurally most com-
plex 6R seems to be the most symmetrical one among the three
hetero[n]rotaxanes, our discussion on the NMR therefore begins
with 6R. The 1H spectrum of 6R contains one set of sharp
signals, suggesting that the [6]rotaxane is adopting a relatively
rigid and symmetrical structure in solution (Figure 2a). NOE
cross peaks between the triazole and CB[6] protons, and also Ha
of the anthracene stoppers and CB[6] protons were observed,
suggesting that the two CB[6] are interlocking at the triazole
which is consistent with the strong binding of the CB[6] to the
ammoniums (Figure S18 in Supporting Information File 1). Due
to the severe peak overlapping in the aliphatic region at
3.5–4.5 ppm, NOE cross peaks in that regions cannot be unam-
biguously assigned and the relative position of the γ-CD on the
axle cannot be further probed without uncertainty. Nevertheless,
with the other three interlocked γ-CD, the biphenylene and the
two tetra(ethylene glycol) parts should all be threaded inside the
γ-CD.
The overall structure of 6R therefore features a specific
CB[6]–(γ-CD)3–CB[6] sequence of the interlocked macro-
cycles. Of note, for a [6]rotaxane with two types of five inter-
locked macrocycles on one axle, there could be in total six dif-
Figure 1: LC–MS analysis of the reaction mixture of the [n]rotaxane
synthesis in the presence of (a) 0.5; (b) 5; (c) 10; (d) 20; and
(e) 50 equiv of γ-CD.
Figure 2: Partial 1H NMR spectra (500 MHz, D2O, 298 K) of (a) 6R; (b) 5R; and (c) 4R.
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ferent possible sequences (Figure 3a). The emergence of only [49]) being complementary in size and showed preferred inter-
one particular sequence here is a result of the specific and or- actions with CB[6] [45]. Nevertheless, more detailed binding
thogonal interactions of the macrocycles with different part of studies and structural characterization will be required for a
the axle. More interestingly, only one set of signals was ob- definitive assignment of the γ-CD orientations and elucidating
served for both the triazole and CB[6] protons in 6R. This ob- the origin of the stereoselectivity in the synthesis of 6R.
servation is suggesting that 1) 6R is adopting a structure that the
CB[6] at the termini are far from the influence of the asym- The 1H spectrum of 4R is generally similar to that of 6R and
metry of the γ-CD in the center; and 2) the two γ-CD next to the strong NOE cross peaks between the triazole and CB[6], and
CB[6] are pointing to the CB[6] with the same face, resulting in also Ha of the anthracene and CB[6] protons were observed
a symmetry plane orthogonal to the axle when the central γ-CD (Figure S10 in Supporting Information File 1), confirming that
is disregarded. Considering that the primary and secondary the two CB[6] are stationing at the ammonium/triazole posi-
faces of a γ-CD are different, there could be four possible orien- tions similar to that in 6R. Yet, there are few significant differ-
tations of the three interlocked γ-CD to give four different tri- ences in the spectrum of 4R noted: 1) two singlets were ob-
azole environments (Figure 3b). Yet, only one of the four served for the triazole; 2) the CB[6] was observed as two differ-
(isomer I or II) possible isomers has been observed in the ent sets of signals; and 3) two pairs of coupled signals and two
1H NMR, suggesting that 6R was obtained as a single stereoiso- singlets were observed for the biphenylene and ArCH2O
mer. In fact, cooperative binding between CB[6] and cyclo- protons (Figure 2b, Figure 4a and Supporting Information
dextrins via hydrogen bonds in rigid (pseudo)rotaxane systems File 1, Figure S7). These observations suggest that the two
has been previously reported [43-48]. The full occupancy of the termini of 4R are more different than that of 6R, which should
axle by five macrocycles and the resulting close proximity of be originated from the asymmetry of the interlocked γ-CD. Al-
the macrocycles in 6R may hence resulted in similar interac- though the hydrophobic biphenylene is expected to form a more
tions that stabilize a particular stereoisomer over the others, stable inclusion complex with γ-CD due to a stronger hydro-
thus making the 6R synthesis stereoselective. Moreover, as the phobic effect, a structure with the γ-CD interlocking at the
secondary face in γ-CD (diameter ≈ 8.3 Å [49]) is much wider central biphenylene of 4R may not explain the non-equivalent
than the rim of CB[6] (diameter ≈ 5.8 Å [50]), it is expected chemical environments of the two termini. As discussed in the
that the primary face of γ-CD (diameter ≈ 7.5 Å [49]) will have structure of 6R above, the central γ-CD at the biphenylene posi-
a better size match and hence a stronger interaction with the tion has little influence on the symmetry of the triazole and
CB[6], and that the two γ-CD adjacent to the CB[6] may be CB[6] at the end of the rotaxane. Together with the relatively
oriented with the primary face towards the anthracene terminal different chemical environments for the two ends of the
[43]. Of note, it has been reported that for the interactions be- biphenylene, the γ-CD in 4R is therefore proposed to be inter-
tween the smaller α-CD and CB[6], it is the wider secondary locking at one of the tetra(ethylene glycol) moieties, possibly as
face of α-CD (diameter ≈ 5.2 Å; primary face diameter ≈ 4.7 Å a result of the stabilizing interactions between the γ-CD and
CB[6]. Indeed, due to the strong interactions between CB[6]
and cyclodextrin, it has been reported that CB[6] can dissemble
a [3]pseudorotaxane consisting of two linear axles bound in the
cavity of a γ-CD to form a [4]pseudorotaxane consisting of one
γ-CD and two CB[6], and that because of the steric hindrance
provided by the CB[6], inclusion of a second guest in the γ-CD
cavity is discouraged [46]. The observation that no rotaxane
product derived from a 2:1 complex of 1/γ-CD was obtained
could also be attributed to a similar steric effect if the CB[6]
and γ-CD are in close proximity, which is also consistent with
the proposed structure of 4R.
Again, the γ-CD is proposed to face the CB[6] with its primary
face due to the better size match and stronger interactions. In
addition, NOE cross peaks between the biphenylene protons
Figure 3: (a) All the possible sequences of a [6]rotaxane with two
and two signals at ca. 3.6–3.8 ppm were observed (Figure 4b).
CB[6] and three γ-CD interlocked on an axle. Only the sequence on
Although the resonances of H2 and H3 are overlapped with that
of the tetra(ethylene glycol) at 3.6–3.8 ppm, no NOE cross peak
between the biphenylene and tetra(ethylene glycol) was ob-
the top left was observed in 6R (with the orientation of the γ-CD disre-
garded). (b) The four possible relative orientations of the three γ-CD in
6R.
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Figure 4: Partial (a) COSY spectrum (500 MHz, D2O, 298 K) and (b) NOESY (500 MHz, D2O, 298 K) of 4R showing the HBPh protons respectively as
two paired of coupled signals and their NOE cross peaks with the H2 and H3 protons.
served in the most flexible 3R (Figure S6 in Supporting Infor- ronment of the central part of the axle and should not give the
mation File 1), suggesting that the observed NOE in 4R are distinct aromatic and ArCH2O signals for the biphenylene.
likely due to a close proximity of the central biphenylene with Indeed, the 1H NMR spectrum of 4R obtained at 338 K showed
the secondary face of the γ-CD, further suggesting the γ-CD is a significant sharpening of Hd and He, and the chemical shifts
interacting with the CB[6] via its narrower primary face. In of the biphenylene aromatic and methylene and CB[6] protons
previous reports of (pseudo)rotaxane systems when a coopera- are less resolved when compared to those resonances observed
tive cyclodextrin and CB[6] binding was observed, an NOE at room temperature, showing probably a faster γ-CD dynamic
correlation between the cyclodextrins and CB[6] protons could at 338 K that averaged out the chemical environments of these
be observed due to their close proximity [45,46]. In our case, protons (Figure S19 in Supporting Information File 1).
due to the severe overlapping of the signals in the aliphatic
region, no clear correlation between the γ-CD and CB[6] could The 1H spectrum of 5R is much more complex. Ha of the
be identified in 4R. Despite of the possibility that the γ-CD anthracene stopper was observed as two overlapping doublets,
could move along the axle and shuttle between the two and three triazole singlets and more than two sets of CB[6]
tetra(ethylene glycol) parts via the biphenylene, this proposal is signals were observed, showing that 5R was obtained as a mix-
not considered as a fast moving γ-CD along the axle on the ture of stereoisomers with very different chemical environ-
NMR timescale will probably average out the chemical envi- ments at the termini. The existence of a stereoisomeric mixture
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of 5R is also consistent with the two closely eluted peaks in the Conclusion
LC chromatogram. Assuming no fast movement of the two In summary, complex hetero[n]rotaxanes have been efficiently
γ-CDs on the axle in 5R as in 4R, there could be six different obtained by using both CB[6] and γ-CD which are interlocked
possible isomers for 5R, and if any γ-CD interlocking at the onto the axle by orthogonal interactions. Of note, the γ-CD in
tetra(ethylene glycol) part is interacting with the CB[6] via its all the rotaxanes are only singly threaded, suggesting that
primary face just as in 4R and 6R, three of the six possible further guest molecules could bind to the γ-CD cavity to give
isomers (IV, V and VI) will be eliminated (Figure 5). If it is interesting host–guest complexes with the [n]rotaxanes as the
further assumed that the γ-CD on the biphenylene has no influ- host, or these [n]rotaxanes being further developed into more
ence on the symmetry of the triazole and CB[6] as discussed complex interlocked structures. Despite of the different possible
above, isomers I and III will both give two sets, whereas the sequences of the interlocked macrocycles, these hetero[n]rotax-
symmetrical isomer II will give one set of triazole and CB[6] anes were obtained with only a specific sequence with the two
signals. The NOESY spectrum of 5R may not provide further CB[6] located at the end. Moreover, the synthesis of 6R is
information due to the complexity of the spectrum (Figure S14 stereoselective and only one stereoisomer was formed, proba-
in Supporting Information File 1), and further structural assign- bly due to the cooperative interactions between the CB[6] and
ment of 5R may not be straightforward unless more detailed the γ-CD on the fully occupied axle of 6R. These findings will
structural characterization such as X-ray crystal data is avail- provide better insight on the use of intercomponent interactions
able. Nevertheless, the observation that 5R was obtained as dif- to control the stereochemistry of complex, multicomponent
ferent stereoisomers further strengthens the proposal that it is rotaxane, catenane and other mechanically interlocked architec-
the full occupancy of the axle by the macrocycles in 6R that tures and the potential applications thereof.
results in a cooperative interaction so that the formation of 6R
is stereoselective. With one less γ-CD in 5R, interactions be-
tween the axle and the macrocycles alone are only enough for
Supporting Information
interlocking the macrocycle, but not sufficient to drive a specif-
Supporting Information File 1
ic orientation of all the γ-CD, suggesting intercomponent stabi-
lization could play an important role in directing higher level
structures in mechanically interlocked molecules, reminiscent to
the intra-strands interactions that stabilize high-order structures
in (bio)polymers.
Detailed experimental procedures of the syntheses and
characterization data (MS, MS2, 1H and 13C NMR spectra).
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-177-S1.pdf]
Figure 5: Possible structures of 5R assuming no fast shuttling of the γ-CD along the axle.
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19.Lim, C. W.; Sakamoto, S.; Yamaguchi, K.; Hong, J.-I. Org. Lett. 2004,
6, 1079–1082. doi:10.1021/ol036127l
20.Kunitake, M.; Kotoo, K.; Manabe, O.; Muramatsu, T.; Nakashima, N.
Chem. Lett. 1993, 22, 1033–1036. doi:10.1246/cl.1993.1033
21.Kasatani, K.; Ohashi, M.; Kawasaki, M.; Sato, H. Chem. Lett. 1987, 16,
1633–1636. doi:10.1246/cl.1987.1633
22.Rao, T. V. S.; Huff, J. B.; Bieniarz, C. Tetrahedron 1998, 54,
10627–10634. doi:10.1016/s0040-4020(98)00597-3
23.Murakami, H.; Kawabuchi, A.; Kotoo, K.; Kunitake, M.; Nakashima, N.
J. Am. Chem. Soc. 1997, 119, 7605–7606. doi:10.1021/ja971438a
24.Murakami, H.; Kawabuchi, A.; Matsumoto, R.; Ido, T.; Nakashima, N.
J. Am. Chem. Soc. 2005, 127, 15891–15899. doi:10.1021/ja053690l
25.Ogata, N.; Sanui, K.; Wada, J. J. Polym. Sci., Polym. Lett. Ed. 1976,
14, 459–462. doi:10.1002/pol.1976.130140803
Acknowledgements
The work described in this paper was supported by the
Croucher Foundation and a grant from the Research Grants
Council of the Hong Kong Special Administrative Region,
China (Early Career Scheme, Project No. HKU 27300014).
JYHM is a recipient of HKU Foundation Postgraduate Fellow-
ship. We acknowledge UGC funding administered by The
University of Hong Kong for support of the Electrospray
Ionization Quadrupole Time-of-Flight Mass Spectrometry
Facilities under support for Interdisciplinary Research in Chem-
ical Science.
26.Maciejewski, M.; Durski, Z. J. Macromol. Sci., Chem. 1981, 16,
441–450. doi:10.1080/00222338108058481
27.Wenz, G.; Keller, B. Angew. Chem., Int. Ed. Engl. 1992, 31, 197–199.
doi:10.1002/anie.199201971
ORCID® iDs
Ho Yu Au-Yeung - https://orcid.org/0000-0002-7216-7921
References
28.Harada, A.; Li, J.; Suzuki, S.; Kamachi, M. Macromolecules 1993, 26,
5267–5268. doi:10.1021/ma00071a047
29.Michels, J. J.; O'Connell, M. J.; Taylor, P. N.; Wilson, J. S.; Cacialli, F.;
Anderson, H. L. Chem. – Eur. J. 2003, 9, 6167–6176.
doi:10.1002/chem.200305245
30.Latini, G.; Parrott, L.-J.; Brovelli, S.; Frampton, M. J.; Anderson, H. L.;
Cacialli, F. Adv. Funct. Mater. 2008, 18, 2419–2427.
doi:10.1002/adfm.200800120
1. Szente, L.; Szejtli, J. Trends Food Sci. Technol. 2004, 15, 137–142.
doi:10.1016/j.tifs.2003.09.019
2. Astray, G.; Gonzalez-Barreiro, C.; Mejuto, J. C.; Rial-Otero, R.;
Simal-Gándara, J. Food Hydrocolloids 2009, 23, 1631–1640.
doi:10.1016/j.foodhyd.2009.01.001
3. Crini, G. Chem. Rev. 2014, 114, 10940–10975. doi:10.1021/cr500081p
4. Davis, M. E.; Brewster, M. E. Nat. Rev. Drug Discovery 2004, 3,
1023–1035. doi:10.1038/nrd1576
31.Yamaguchi, I.; Kashiwagi, K.; Yamamoto, T.
5. Loftsson, T.; Brewster, M. E. J. Pharm. Pharmacol. 2010, 62,
1607–1621. doi:10.1111/j.2042-7158.2010.01030.x
6. Gattuso, G.; Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev. 1998, 98,
1919–1958. doi:10.1021/cr960133w
Macromol. Rapid Commun. 2004, 25, 1163–1166.
doi:10.1002/marc.200400024
32.Ke, C.; Smaldone, R. A.; Kikuchi, T.; Li, H.; Davis, A. P.; Stoddart, J. F.
Angew. Chem., Int. Ed. 2013, 52, 381–387.
7. Saenger, W.; Jacob, J.; Gessler, K.; Steiner, T.; Hoffmann, D.;
Sanbe, H.; Koizumi, K.; Smith, S. M.; Takaha, T. Chem. Rev. 1998, 98,
1787–1802. doi:10.1021/cr9700181
doi:10.1002/anie.201205087
33.Klotz, E. J. F.; Claridge, T. D. W.; Anderson, H. L. J. Am. Chem. Soc.
2006, 128, 15374–15375. doi:10.1021/ja0665139
8. Connors, K. A. Chem. Rev. 1997, 97, 1325–1358.
doi:10.1021/cr960371r
9. Rekharsky, M. V.; Inoue, Y. Chem. Rev. 1998, 98, 1875–1918.
doi:10.1021/cr970015o
10.Ueno, A.; Takahashi, K.; Osa, T. J. Chem. Soc., Chem. Commun.
1980, 921–922. doi:10.1039/c39800000921
11.Rao, K. S. S. P.; Hubig, S. M.; Moorthy, J. N.; Kochi, J. K.
J. Org. Chem. 1999, 64, 8098–8104. doi:10.1021/jo9903149
12.Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev. 1998, 98, 1959–1976.
doi:10.1021/cr970049w
13.Armspach, D.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Godi, A.;
Moore, C. P.; Prodi, L.; Spencer, N.; Stoddart, J. F.; Tolley, M. S.;
Wear, T. J.; Williams, D. J.; Stoddart, J. F. Chem. – Eur. J. 1995, 1,
33–55. doi:10.1002/chem.19950010109
14.Wenz, G.; Han, B.-H.; Müller, A. Chem. Rev. 2006, 106, 782–817.
doi:10.1021/cr970027+
15.Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46,
72–191. doi:10.1002/anie.200504313
16.Ogino, H. J. Am. Chem. Soc. 1981, 103, 1303–1304.
doi:10.1021/ja00395a091
34.Inouye, M.; Hayashi, K.; Yonenaga, Y.; Itou, T.; Fujimoto, K.;
Uchida, T.-a.; Iwamura, M.; Nozaki, K. Angew. Chem., Int. Ed. 2014,
53, 14392–14396. doi:10.1002/anie.201408193
35.Yu, X.; Liang, W.; Huang, Q.; Wu, W.; Chruma, J. J.; Yang, C.
Chem. Commun. 2019, 55, 3156–3159. doi:10.1039/c9cc00097f
36.Okada, M.; Takashima, Y.; Harada, A. Macromolecules 2004, 37,
7075–7077. doi:10.1021/ma0489220
37.Yee, C.-C.; Ng, A. W. H.; Au-Yeung, H. Y. Chem. Commun. 2019, 55,
6169–6172. doi:10.1039/c9cc02263e
38.Au-Yeung, H. Y.; Yee, C.-C.; Ng, A. W. H.; Hu, K. Inorg. Chem. 2018,
57, 3475–3485. doi:10.1021/acs.inorgchem.7b02523
39.Wang, K.; Yee, C.-C.; Au-Yeung, H. Y. Chem. Sci. 2016, 7,
2787–2792. doi:10.1039/c5sc04774a
40.Mock, W. L.; Irra, T. A.; Wepsiec, J. P.; Manimaran, T. L. J. Org. Chem.
1983, 48, 3619–3620. doi:10.1021/jo00168a070
41.Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001,
40, 2004–2021.
doi:10.1002/1521-3773(20010601)40:11<2004::aid-anie2004>3.0.co;2-
5
42.Sinha, M. K.; Reany, O.; Yefet, M.; Botoshansky, M.; Keinan, E.
Chem. – Eur. J. 2012, 18, 5589–5605. doi:10.1002/chem.201103434
43.Hou, X.; Ke, C.; Stoddart, J. F. Chem. Soc. Rev. 2016, 45, 3766–3780.
doi:10.1039/c6cs00055j
17.Ogino, H.; Ohata, K. Inorg. Chem. 1984, 23, 3312–3316.
doi:10.1021/ic00189a009
18.Armspach, D.; Ashton, P. R.; Moore, C. P.; Spencer, N.;
Stoddart, J. F.; Wear, T. J.; Williams, D. J.
44.Branná, P.; Černochová, J.; Rouchal, M.; Kulhánek, P.; Babinský, M.;
Marek, R.; Nečas, M.; Kuřitka, I.; Vícha, R. J. Org. Chem. 2016, 81,
9595–9604. doi:10.1021/acs.joc.6b01564
Angew. Chem., Int. Ed. Engl. 1993, 32, 854–858.
doi:10.1002/anie.199308541
1836

Beilstein J. Org. Chem. 2019, 15, 1829–1837.
45.Rekharsky, M. V.; Yamamura, H.; Kawai, M.; Osaka, I.; Arakawa, R.;
Sato, A.; Ko, Y. H.; Selvapalam, N.; Kim, K.; Inoue, Y. Org. Lett. 2006,
8, 815–818. doi:10.1021/ol0528742
46.Yang, C.; Ko, Y. H.; Selvapalam, N.; Origane, Y.; Mori, T.; Wada, T.;
Kim, K.; Inoue, Y. Org. Lett. 2007, 9, 4789–4792.
doi:10.1021/ol702142j
47.Yan, Z.; Huang, Q.; Liang, W.; Yu, X.; Zhou, D.; Wu, W.; Chruma, J. J.;
Yang, C. Org. Lett. 2017, 19, 898–901.
doi:10.1021/acs.orglett.7b00057
48.Dai, L.; Wu, W.; Liang, W.; Chen, W.; Yu, X.; Ji, J.; Xiao, C.; Yang, C.
Chem. Commun. 2018, 54, 2643–2646. doi:10.1039/c8cc00840j
49.Locke, D.; Koreen, I. V.; Liu, J. Y.; Harris, A. L. J. Biol. Chem. 2004,
279, 22883–22892. doi:10.1074/jbc.m401980200
50.Lee, J. W.; Samal, S.; Selvapalam, N.; Kim, H.-J.; Kim, K.
Acc. Chem. Res. 2003, 36, 621–630. doi:10.1021/ar020254k
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