A compatibility study on the glycosylation of 4,4′-dihydroxyazobenzene

Article abstract of DOI:10.1039/d0ra02435j

Photoresponsive glycoconjugates based on the azobenzene photoswitch are valuable molecules which can be used as tools for the investigation of carbohydrate-protein interactions or as precursors of shape-switchable molecular architectures, for example. To access such compounds, glycosylation of 4,4′-dihydroxyazobenzene (DHAB) is a critical step, frequently giving heterogeneous results because DHAB is a challenging glycosyl acceptor. Therefore, DHAB glucosylation was studied using nine different glycosyl donors, and reaction conditions were systematically varied in order to find a reliable procedure, especially towards the preparation of azobenzene bis-glucosides. Particular emphasis was put on glucosyl donors which were differentiated at the primary 6-position (N₃, OAc) for further functionalisation. The present study allowed us to identify suitable glycosyl donors and reaction conditions matching with DHAB, affording the bis-glycosylated products in fair yields and good stereocontrol.

Full text of DOI:10.1039/d0ra02435j

RSC Advances
View Article Online
View Journal | View Issue
PAPER
A compatibility study on the glycosylation of 4,40-
dihydroxyazobenzene†
Cite this: RSC Adv., 2020, 10, 17432
*
*
Jonathan Berry, Guillaume Despras
and Thisbe K. Lindhorst
Photoresponsive glycoconjugates based on the azobenzene photoswitch are valuable molecules which
can be used as tools for the investigation of carbohydrate–protein interactions or as precursors of
shape-switchable molecular architectures, for example. To access such compounds, glycosylation of
4,40-dihydroxyazobenzene (DHAB) is a critical step, frequently giving heterogeneous results because
DHAB is a challenging glycosyl acceptor. Therefore, DHAB glucosylation was studied using nine different
glycosyl donors, and reaction conditions were systematically varied in order to find a reliable procedure,
especially towards the preparation of azobenzene bis-glucosides. Particular emphasis was put on
glucosyl donors which were differentiated at the primary 6-position (N3, OAc) for further
functionalisation. The present study allowed us to identify suitable glycosyl donors and reaction
conditions matching with DHAB, affording the bis-glycosylated products in fair yields and good
stereocontrol.
Received 16th March 2020
Accepted 22nd April 2020
DOI: 10.1039/d0ra02435j
rsc.li/rsc-advances
molecular moieties ligated to both ends of the azobenzene. In
glycobiology, this has been employed to study carbohydrate–
Introduction
Since their historical use as dyes,1 azobenzene derivatives have
received great interest as photosensitive molecular switches.2
This is due to the fact that the azobenzene N]N double bond
gives rise to two isomeric forms, a trans (E) and a cis (Z) isomer,
which can be reversibly interchanged by light of different
wavelengths.2 Moreover, substitution of the phenyl rings allows
modication and ne-tuning of the photochromic properties of
azobenzene photoswitches.
The phenyl rings of azobenzene derivatives can be further
functionalised in order to include the photoswitch into various
molecular architectures and probes. Hence, the azobenzene
hinge has found applications in liquid crystals,3 fast
information-transmitting materials,4 photoswitchable cata-
lysts,5 or actuators.6 Azobenzene photoswitches were also
extensively used in supramolecular chemistry, in particular in
light-driven molecular machines,7 and importantly, they were
incorporated into biomolecules,2b,8 such as peptides9 and
proteins,10 nucleic acids,11 lipids,12 and also carbohy-
drates3b–d,13,14,15,16 to enable photocontrol of molecular features
and biological activity.
lectin interactions in relation to the spatial presentation of the
connected glyco ligands. In 2002, Jayaraman et al. rst
described the synthesis of azobenzene glycoconjugates and
their investigation in lectin binding studies.17 Since then, azo-
benzene glycoconjugates have gained increasing interest in the
glycosciences. Our group has recently mounted azobenzene
glycoconjugates onto gold surfaces in the form of glyco-SAMs
(self-assembled monolayers).18 Here, the azo group was
employed as a molecular hinge in order to switch the orienta-
tion of a-D-mannoside ligands terminating the SAMs (Fig. 1b).
By photoisomerization, the orientation of the sugar ligands on
the surface can be altered, allowing for the control of mannose-
specic adhesion of bacterial cells.19 More recently, we have
introduced photoresponsive glycoazobenzene macrocycles
(Fig. 1c), which are shape-switchable and capable of reversible
modication of chiroptical or solubility properties.20 Along the
same lines, J. Xie and colleagues reported the synthesis of
azobenzene glycomacrolactones.21
In such work, the glycosylation of hydroxy-functionalised
azobenzene served as a key step in the direct conjugation of
the carbohydrate moiety and the photoswitchable azobenzene
unit. We have typically employed O-glycosyl tri-
chloroacetimidates as glycosyl donors to achieve azobenzene
glycosides in good yields.18,22 However, the bis-glycosylation of
4,40-dihydroxyazobenzene (DHAB), as it was used for the prep-
aration of azobenzene glycomacrocycles for example (Fig. 1c), is
frequently impaired by poor to moderate yields.10d,20a This is due
to the decreased nucleophilicity of the hydroxy groups in para-
positions of the azobenzene, which is based on a tautomerism
As the distance between the two para-positions of azo-
˚
˚
benzene varies between roughly 9 A in the trans state and 5.5 A
in the cis form (Fig. 1a), isomerisation of the N]N double bond
offers an opportunity to switch the relative orientation of
Otto Diels Institute of Organic Chemistry, Christiana Albertina University of Kiel,
Otto-Hahn-Platz 3/4, 24118 Kiel, Germany. E-mail: tklind@oc.uni-kiel.de
† Electronic supplementary information (ESI) available. See DOI:
10.1039/d0ra02435j
17432 | RSC Adv., 2020, 10, 17432–17437
This journal is © The Royal Society of Chemistry 2020

View Article Online
Paper
RSC Advances
Fig. 1 Photoisomerisation of azobenzene and examples of photoresponsive glycoconjugates. (a) Light or heat-induced isomerisation of azo-
benzene; (b) mannosylation of hydroxyazobenzene mounted onto a surface leads to glyco-SAMs where glyco ligand orientation can be pho-
toswitched; (c) glycosylation of 4,40-dihydroxyazobenzene (DHAB) leads to shape-switchable glycoazobenzene macrocycles; (d) tautomeric
equilibrium of DHAB with its hydrazoquinone form and possible intermolecular hydrogen bonding promoting the hydrazoquinone tautomer.
with the corresponding hydrazoquinone form, affecting both
para-OH groups in DHAB (Fig. 1d). This tautomerism is donors 3 and 7 started from levoglucosan (Scheme 1), which
promoted by intermolecular hydrogen bonds.23
was rst perbenzoylated with benzoyl chloride in pyridine to
The preparation of the 6-azido-6-deoxy-modied glucosyl
We gured that, in order to improve the yields of DHAB bis- give 11 in 92% yield. Subsequent opening of the protected 1,6-
glycosides and to broaden the scope of azobenzene glycosides, anhydroglucose with (phenylthio)trimethylsilane (TMSSPh) in
we would have to study alternative glycosylation methods rather the presence of zinc iodide at 120 ꢀC under microwave heating
than to modify the azobenzene acceptor diol. Consequently, we gave thioglucoside 12 in 98% yield with complete b-selectivity.
commenced
a study on the bis-glycosylation of DHAB, Then, the free primary hydroxy group was substituted by an
employing different glucosyl donors with variation of the azide under Bose-Mitsunobu25 conditions to afford 3 in 71%
anomeric leaving group as well as protecting groups. We were yield. Trichlorocyanuric acid (TCCA)-promoted hydrolysis of 3
especially interested to improve the yields of DHAB bis- in an acetone/water mixture yielded the reducing intermediate,
glycosylation with 6-azido-6-deoxy-functionalised glucosyl which in turn reacted with (N-phenyl)triuoroacetimidoyl
donors, as 6-functionalisation enables incorporation of the chloride under basic conditions to provide the glucosyl donor 7
glycoazobenzene switch into larger molecular constructs.20a
in 76% yield over two steps.
Results and discussion
Preparation of glucosyl donors
Four common types of glucosyl donors were investigated in the
glycosylation of DHAB, thioglucosides, glucosyl bromides, glu-
cosyl sulfoxides, and O-glucosyl acetimidates (Chart 1). In most
cases, the sugar hydroxy groups were protected as acetyl or
benzoyl esters, respectively, to guarantee the stereoselective
formation of 1,2-trans-glucosides based on the participating
effect of the 2-O-acyl group. Two of the employed donors were
silylated to achieve so-called super-armed glycosyl donors (vide
infra).24
The glucosyl donors 1, 2, 4, 5 and 6 were prepared starting
from D-glucose according to standard procedures (cf. ESI†).
Chart 1 Structures of glycosyl donors used in the present study.
RSC Adv., 2020, 10, 17432–17437 | 17433
This journal is © The Royal Society of Chemistry 2020

View Article Online
RSC Advances
Paper
Glycosylations
Then, with nine different glucosyl donors in hand (cf. Chart 1),
the bis-glycosylation of DHAB27 was investigated (Scheme 2).
The results are summarized in Table 1. In previous work, O-
glycosyl trichloroacetimidates were used for DHAB bis-
glycosylation giving rise to yields between 30 and maximal
50%.10d,20a In order to improve the bis-glycosylation of DHAB, we
rst assessed glucosyl bromide 1, as silver salts, which are
employed to activate Koenigs–Knorr-type glycosyl donors,
should be compatible with an azobenzene acceptor. However,
regardless of whether silver carbonate or silver oxide was used
as promoter,28 only hydrolysis of the glucosyl donor occurred
while the acceptor was nearly fully recovered (Table 1, entry 1).
Next, we employed thioglucosides, as these donors present
several great advantages; indeed thioglycosides are bench-
stable, can be easily prepared in high yields and are compat-
ible with a wide range of reaction conditions. When the acetyl-
protected donor 2 was reacted under standard N-iodosuccini-
mide (NIS)/triic acid (TfOH) activation,29 complete donor
hydrolysis was observed (entry 2). When NIS was replaced by
NBS (N-bromosuccinimide) a similar result was observed (entry
3). In both cases various DHAB-derived side products were
formed, including the N-dehydro-N-iodohydrazoquinone
tautomer (cf. ESI†). These results indicate that, the azophenol/
hydrazoquinone tautomerism of DHAB (cf. Fig. 1d) not only
effects a decreased oxygen nucleophilicity but also increases the
nucleophilicity of the nitrogen atoms of the azo group. Hence,
especially with so electrophiles such as iodonium ions, N-
halogenation of the azo group competes with the activation of
the glycosyl donor and inhibits the reactivity of the acceptor.
As it was not possible to activate thioglycosides with
halogenium-donating promoters, the benzoylated thioglucoside 3
was activated with methyl triate (MeOTf)30 or dimethyl(me-
thylthio)sulfonium triate (DMTST).31 Bearing the azophenol/
hydrazoquinone tautomerism in mind, we gured that acidic
media may favor the formation of the hydrazoquinone tautomer.
Therefore, we buffered the following glycosylation reactions with
2,6-di-tert-butyl-4-methylpyridine (DTBMP), which is known as an
effective proton scavenger. Unfortunately, glycosylation of DHAB
with 3 under these conditions (entries 4 and 5) failed. While the
glucosyl donor was hydrolyzed or remained unreacted, again
a number of DHAB-derived by-products were formed, presumably
including O-methylated derivatives. The disappointing results
with the thioglycosides led us to consider the glucosyl sulfoxide 4
as glycosyl donor, as it should be effective for the glycosylation of
Scheme 1 Preparation of glucosyl donors 3 and 7–9. Reagents and
conditions: (a) BzCl (6 eq.), pyridine, rt, 92%; (b) ZnI2 (4 eq.), TMSSPh
(2.5 eq.), CH2Cl2, mW (150 W), 120 ꢀC, 25 min, 98%; (c) PPh3 (1.5 eq.),
DIAD (2.5 eq.), DPPA (1.5 eq.), THF, ꢁ15 ꢀC to rt, 71%; (d) TCCA (1 eq.),
acetone/H2O (9 : 1), rt; (e) ClC(NPh)CF3 (1.5 eq.), Cs2CO3 (1.5 eq.),
CH2Cl2, rt, 76% over 2 steps; (f) TBSCl (6 eq.), NMI (7 eq.), I2 (2.5 eq.),
pyridine, rt, 80%; (g) ZnI2 (4 eq.), TMSSPh (2.5 eq.), CH2Cl2, rt, 96%; (h)
Ac2O (1.5 eq.), DMAP (0.2 eq.), pyridine, rt, 95%; (i) PPh3 (1.5 eq.), DIAD
(2.5 eq.), DPPA (1.5 eq.), THF, ꢁ15 ꢀC to rt, 85%; DIAD ¼ diisopropyl
azodicarboxylate; DPPA ¼ diphenylphosphorylazide; TCCA ¼ tri-
chlorocyanuric acid; TBSCl ¼ t-butyldimethylchlorosilane; NMI ¼ N-
methylimidazole; TMSSPh ¼ (phenylthio)trimethylsilane.
In analogy to the preparation of 11, persilylation of levoglu-
cosan was envisaged for the synthesis of the silylated glucosyl
donors 8 and 9. However, this reaction step required an opti-
mization (cf. ESI†) to avoid the formation of the undesired 2,4-
disilyated levoglucosan derivative. Finally, the persilylated lev-
oglucosan derivative 13 was obtained in 80% yield by the
addition of iodine to a mixture of 10, TBSCl and N-methyl-
imidazole in pyridine.26
When the following ring opening step with 13 was performed
under microwave heating as employed for the acyl-protected
analogue 11, degradation was observed. Lowering the reaction
ꢀ
temperature to 80 C only slightly improved the reaction, but
when the reaction was carried out at room temperature, it
afforded the desired 6-OH-free thioglucoside 14 in 96% yield as
an anomeric mixture (a : b ¼ 1 : 4). This result complies with
the higher reactivity of the armed silylated sugar derivatives in
comparison to disarmed acylated analogues. The primary
alcohol function in 14 was then acetylated to afford the glucosyl
donor 8 in 95% yield, and the targeted 6-azido-6-deoxy glucosyl
donor
9 was obtained in 85% under Bose-Mitsunobu
conditions.
Scheme 2 Glycosylation of DHAB with different glycosyl donors. The desired bis-glucosylated products are numbered with “a”, the mono-
glycosylated by-products with “b”.
17434 | RSC Adv., 2020, 10, 17432–17437
This journal is © The Royal Society of Chemistry 2020

View Article Online
Paper
RSC Advances
Table 1 Glycosylation of DHAB with donors 1–9 under various conditionsa
Bis-glycoside, yield, ab : bb,
monoglycoside, yield, a : b
Entry
Donorb
Promoter (eq./donor)
Base (eq./DHAB)
Solvent
Temp.
rt
1
2
3
4
5
6
7
8
1
2
2
3
3
4c
5
6
7
8
8
8
8
9
Ag2CO3 (1.1) or Ag2O (2)
NIS/TfOH (1.5/0.05)
NBS/TfOH (1.5/0.1)
MeOTf (3.0)
DMTST (1.5)
Tf2O (1.0)
BF3$OEt2 (1.1)
BF3$OEt2 (1.1)
BF3$OEt2 (1.1)
MeOTf (3.0)
MeOTf (3)
MeOTf (3)
—
—
—
MeCN
MeCN
MeCN
CH2Cl2
CH2Cl2
CH2Cl2
MeCN
MeCN
MeCN
CH2Cl2
MeCN
CH2Cl2/[bmim][OTf] (10 : 1)
CH2Cl2/[bmim][OTf] (9 : 1)
CH2Cl2
Donor hydrolysis
Donor hydrolysis
Donor hydrolysis
Donor hydrolysis
No activation
Donor hydrolysis
15a, 68%, 0 : 1, 15b, not observed
16a, 48%, 0 : 1, 16b, 14%, 0 : 1
17a, 38%, 0 : 1, 17b, 25%, 0 : 1
18a, 50%, 1 : 5, 18b, 20%, 1 : 10
18b, 17%, 1 : 5
18a, 7%, 1 : 6, 18b, 31%, 1 : 12
18a, 18% 1 : 10, 18b, 12% 1 : 5
19a, 10%, 1 : 4, 19b, 14%, 1 : 8
0 ꢀ
rt
C
DTBMP (2.2)
DTBMP (2.2)
DTBMP (3)
—
—
—
DTBMP (2.2)
DTBMP (2.2)
DTBMP (2.2)
DTBMP (2.2)
DTBMP (2.2)
rt
ꢁ30 ꢀ
ꢁ78 ꢀ
rt
C
C
rt
rt
rt
rt
9
10
11
12
13d
14
rt
BSP/Tf2O (2.2/2.2)
MeOTf (3.0)
ꢁ90 ꢀ
rt
C
a
All reactions were performed under dry conditions with addition of 3 A molecular sieves (MS) and with [DHAB] ¼ 0.05 mol ꢂ Lꢁ1 unless otherwise
stated. b 2.2 eq. of donor were used unless otherwise stated. c 4 eq. of donor were used. d A solution of the acceptor was added to a mixture of donor
and promoter; DTBMP ¼ 2,6-di-tert-butyl-4-methylpyridine; DMTST ¼ dimethyl(methylthio)sulfonium triuoromethanesulfonate; [bmim][OTf] ¼
˚
1-butyl-3-methylimidazolium triuoromethanesulfonate; BSP
bromosuccinimide.
¼
1-benzenesulnyl piperidine; NIS
¼
N-iodosuccinimide; NBS
¼
N-
unreactive alcohols according to Kahne.32 When DHAB was (ab : bb ¼ 1 : 5) and 20% of the monoglycosylated compound
treated with 4 in the presence of triic anhydride (Tf2O) and 18b (a : b ¼ 1 : 10) were obtained, however as anomeric
DTBMP at ꢁ78 ꢀC, the donor was completely consumed aer 1 h, mixtures. As DHAB is only partially soluble in CH2Cl2, 8 was
presumably transformed into the corresponding triate, while employed under identical conditions but in acetonitrile (entry
DHAB remained unreacted (entry 6). Prolonging the reaction time 11), and this reaction furnished the monoglycosylated product
and increasing the temperature led to the hydrolyzed donor and 19b in 17% yield as the sole glycoside along with methylated
the unreacted acceptor. Even though Kahne et al. have described DHAB derivatives.33 This result indicates that the low solubility
the successful glycosylation of sterically hindered and electroni- of DHAB in CH2Cl2 favors glycosylation over methylation of the
cally deactivated phenols with sulfoxides, this method was not phenol OH group as well as bis-glycosylation over mono-
successful with DHAB, again underlining the limited reactivity of glycosylation. Compared to the glycosylation in CH2Cl2, the
this azobenzene diol.
a : b ratio of 19b which was obtained in acetonitrile is some-
Next, we turned our attention to the O-(glucosyl)-N-phenyl- what unexpected. As acetonitrile is known as a participating
triuoroacetimidate donors. Indeed, the acetylated donor 5 solvent, an a-nitrilium intermediate should occur, favoring the
under BF3-etherate activation afforded satisfying 68% of the formation of the b-anomer.
desired bis-glycosylated compound 15a as a single bb-anomer
(entry 7). The monoglycosylated product 15b was not formed.
Next several buffering bases were assessed (cf. ESI†). While
none of the investigated bases led to a convincing improvement of
Aer this encouraging result, the same method was the yields or anomeric selectivities, DTBMP was the base of choice
employed to introduce a 6-azido function into the azobenzene to avoid the undesired O-methylation of DHAB. We also examined
glycoside using the 6-azido-6-deoxy-functionalised glucosyl the use of the ionic liquid 1-butyl-3-methylimidazolium tri-
donor 6 (entry 8). This reaction was again successful, however uoromethanesulfonate ([bmim][OTf]) as a co-solvent in CH2Cl2.34
with lower yields, 48% of 16a and 14% of the monoglycosylated In this solvent mixture, DHAB is completely dissolved and the
16b, again under complete b-selectivity. The benzoyl-protected activation of the thioglycoside 8 with MeOTf in the presence of
analogue of 6, the acetimidate 7, under the same conditions DTBMP (entry 12) again favored the monoglycosylated product 19b
led to slightly lower yields, affording the pure bb-anomer 17a in (31%) with a good anomeric selectivity (a : b ¼ 1 : 12), while 19a
38% along with 25% of pure b-monoglycosylated 17b (entry 9). was isolated in only 7% yield. As observed for the reaction in
At this stage of the study, the armed thioglycosides 8 and 9 acetonitrile, O-methylated derivatives of DHAB were formed.
were assessed for the bis-glycosylation of DHAB. As a conclusion Interestingly, the promoter system 1-benzenesulnyl piperidine
from the results obtained with the disarmed thioglucosides (BSP)/Tf2O35 could efficiently activate donor 8 without reacting with
(entries 2–5), MeOTf was chosen for the activation. In addition, the DHAB acceptor (entry 13). This reaction provided 19a in 18%
in order to avoid acid-mediated intermolecular silyl transfer, yield (ab : bb ¼ 1 : 10) and 19b in 12% (a : b ¼ 1 : 5).
the reaction medium was buffered with DTBMP. Satisfyingly,
Then, the 6-azido-functionalised donor 9 was assessed under
when DHAB was reacted with the armed donor 8 under these the glycosylation conditions which were found optimal for the
conditions (entry 10), 50% of the bis-glycosylated product 18a armed donor 8 (entry 10). This reaction afforded the bis-
This journal is © The Royal Society of Chemistry 2020
RSC Adv., 2020, 10, 17432–17437 | 17435

View Article Online
RSC Advances
Paper
glycoside 20a in 10% yield (ab : bb ¼ 1 : 4) and the mono-
glycosylated compound 20b in 14% yield (a : b ¼ 1 : 8) (entry
14). When the BSP/Tf2O system was applied with donor 9 only
hydrolysis was observed. As observed with the acylated donors 6
and 7, the 6-azido group seems to have a detrimental effect on
the glycosylation of DHAB. This is consistent with previous
reports of glycosylations involving 6-azido-6-deoxy-glycosyl
donors and different kinds of phenolic acceptors, yielding the
products in low to moderate yields.10c,d,20a,36,37
Notes and references
1 H. Zollinger, in Color Chemistry: Syntheses, Properties and
Applications of Organic Dyes and Pigments, ed. P. M.
Wallimann, Wiley-VCH, Weinheim, 2003, vol. 7, pp. 165–
254.
2 (a) H. M. D. Bandara and S. C. Burdette, Chem. Soc. Rev.,
2012, 41, 1809–1825; (b) A. A. Beharry and G. A. Woolley,
Chem. Soc. Rev., 2011, 40, 4422–4437.
3 (a) L. Johnson, B. Ringstrand and P. Kaszynski, Liq. Cryst.,
2009, 36, 176–185; (b) N. Laurent, D. Lafont, F. Dumoulin,
P. Boullanger, G. Mackenzie, P. H. Kouwer and
J. W. Goodby, J. Am. Chem. Soc., 2003, 125, 15499–15506;
(c) A. G. Cook, J. L. Wardell, N. J. Brooks, J. M. Seddon,
Conclusions
We carefully investigated the glycosylation of 4,40-dihydrox-
yazobenzene with a range of glycosyl donors displaying
different reactivities. Our study provided useful data to delin-
eate the scope and limitations of this glycosylation reaction and
allows to foresee mismatch cases for DHAB. Four main features
are underpinned by our results. First, DHAB is a poorly reactive
acceptor, mainly because the nucleophilicity of the phenolic
hydroxy groups is lowered by a tautomeric equilibrium between
the azophenol and the hydrazoquinone form. Second, this
tautomerism may increase the nucleophilicity of the nitrogen
atoms in the azo bond, which leads to N-halogenation when
halogenium-providing promoters are used. Third, when glyco-
sylations are carried out in a buffered medium with electro-
philic activators such as MeOTf or DMTST, the choice of the
base is crucial to prevent competing O-methylation of DHAB.
Fourth, the solubility of DHAB is an important parameter to
control the degree of DHAB glycosylation. The lower the solu-
bility of DHAB, the higher the yield of bis-glycosylated product.
In conclusion, we believe our work reveals a new facet of the
complexity of glycosylation reactions. Here, the azobenzene
derivative DHAB was in the focus of our work and although
glycosylation of DHAB remains challenging, we have identied
glycosyl donors and activation methods compatible for the bis-
glycosylation of this important photoswitch. In particular, the
use of silyl-protected thioglycosides which are differentiated at
the primary 6-position of the sugar ring is promising for the
preparation of photoswitchable glycoconjugates and macro-
cycles. Efforts will be made for improving the glycosylation
efficiency, regarding both stereoselectivity and degree of
substitution, by varying the silyl protecting groups, the nature of
the functional group at position 6 and further nely tune the
reaction conditions.
´
A. Martınez-Felipe and C. T. Imrie, Carbohydr. Res., 2012,
360, 78–83; (d) S. Abraham, S. Paul, G. Narayan,
S. K. Prasad, D. S. Rao, N. Jayaraman and S. Das, Adv.
Funct. Mater., 2005, 15, 1579–1584.
´
´
4 J. Gavıa-Amoros and D. Velasco, Beilstein J. Org. Chem., 2012,
8, 1003–1017.
5 P. Viehmann and S. Hecht, Beilstein J. Org. Chem., 2012, 8,
1825–1830.
6 E. Merino and M. Ribagorda, Beilstein J. Org. Chem., 2012, 8,
1071–1090.
7 (a) E. Wagner-Wysiecka, N. Łukasik and J. F. Biernat, J.
Inclusion Phenom. Macrocyclic Chem., 2018, 90, 189–257; (b)
C. Gao, X. Ma, Q. Zhang, Q. Wang, D. Qu and H. Tian, Org.
Biomol. Chem., 2011, 9, 1126–1132; (c) Y. Inoue, P. Kuad,
Y. Okumura, Y. Takashima, H. Yamaguchi and A. Harada,
J. Am. Chem. Soc., 2007, 129, 6396–6397.
8 M. Dong, A. Babalhavaeji, S. Samanta, A. A. Beharry and
G. A. Woolley, Acc. Chem. Res., 2015, 48, 2662–2670.
¨
9 (a) C. Renner, U. Kusebauch, M. Loweneck, A. G. Milbradt
and L. Moroder, J. Pept. Res., 2005, 65, 4–14; (b)
G. A. Woolley, Acc. Chem. Res., 2005, 38, 486–493.
10 (a) H. Kaufman, S. M. Vratsanos and B. F. Erlanger, Science,
1968, 162, 1487–1489; (b) I. Willner, S. Rubin and A. Riklin, J.
¨
Am. Chem. Soc., 1991, 113, 3321–3325; (c) A. Muller and
T. K. Lindhorst, Eur. J. Org. Chem., 2016, 1669–1672; (d)
¨
A. Muller, H. Kobarg, V. Chandrasekaran, J. Gronow,
¨
F. D. Sonnichsen and T. K. Lindhorst, Chem.–Eur. J., 2015,
21, 13723–13731.
11 A. Heckel and G. Mayer, in The Chemical Biology of Nucleic
Acids, ed. G. Mayer, Wiley-VCH, Chichester, 2010, vol. 13,
pp. 279–306.
12 (a) J. Y. Wang, Q. F. Wu, J. P. Li, Q. S. Ren, Y. L. Wang and
X. M. Liu, Mini-Rev. Med. Chem., 2010, 10, 172–181; (b)
A. Yavlovich, B. Smith, K. Gupta, R. Blumenthal and
A. Puri, Mol. Membr. Biol., 2010, 27, 364–381.
13 (a) F. Hamon, F. Djedaini-Pilard, F. Barbot and C. Len,
Tetrahedron, 2009, 65, 10105–10123; (b) Y. Hu, R. F. Tabor
and B. L. Wilkinson, Org. Biomol. Chem., 2015, 13, 2216–
2225.
Conflicts of interest
There are no conicts of interest to declare about the authors.
Acknowledgements
Financial support by the DFG (collaborative network SFB677)
and FCI (Fonds der Chemischen Industrie) is gratefully
acknowledged.
14 H. Kobayashi, A. Friggeri, K. Koumoto, M. Amaike,
S. Shinkai and D. N. Reinhoudt, Org. Lett., 2002, 4, 1423–
1426.
17436 | RSC Adv., 2020, 10, 17432–17437
This journal is © The Royal Society of Chemistry 2020

View Article Online
Paper
RSC Advances
´
15 (a) N. Drillaud, E. Banaszak-Leonard, I. Pezron and C. Len, J. 26 A. Bartoszewicz, M. Kalek, J. Nilsson, R. Hiresova and
Org. Chem., 2012, 77, 9553–9561; (b) R. F. Tabor, J. Stawinski, Synlett, 2008, 1, 37–40.
M. J. Pottage, C. J. Garvey and B. L. Wilkinson, Chem. 27 DHAB was prepared according to H. Tokuhisa, M. Yokoyama
Commun., 2015, 51, 5509–5512.
and K. Kimura, Bull. Chem. Soc. Jpn., 1996, 69, 2123–2130.
28 W. Koenigs and E. Knorr, Ber. Dtsch. Chem. Ges., 1901, 34,
957–981.
29 (a) G. H. Vwneman, S. H. van Leeuwen and J. H. van Boom,
Tetrahedron Lett., 1990, 31, 1331–1334; (b) P. Konradsson,
U. E. Udodong and B. Fraser-Reid, Tetrahedron Lett., 1990,
31, 4313–4316.
16 P. V. Jog and M. S. Gin, Org. Lett., 2008, 10, 3693–3696.
17 O. Srinivas, N. Mitra, A. Surolia and N. Jayaraman, J. Am.
Chem. Soc., 2002, 124, 2124–2125.
18 (a) V. Chandrasekaran, H. Jacob, F. Petersen, K. Kathirvel,
F. Tuczek and T. K. Lindhorst, Chem.–Eur. J., 2014, 20,
¨
8744–8752; (b) E. Fast, A. Schlimm, I. Lautenschlager,
¨
K. U. Clausen, T. Strunskus, C. Spormann, T. K. Lindhorst 30 H. Lonn, Carbohydr. Res., 1985, 139, 105–113.
¨
and F. Tuczek, Chem.–Eur. J., 2020, 26, 485–501. 31 P. Fugedi and P. J. Garegg, Carbohydr. Res., 1986, 149, 9–12.
19 T. Weber, V. Chandrasekaran, I. Stamer, M. B. Thygesen, 32 D. Kahne, S. Walker, Y. Cheng and D. Van Engen, J. Am.
A. Terfort and T. K. Lindhorst, Angew. Chem., Int. Ed., 2014,
53, 14583–14586.
20 (a) G. Despras, J. Hain and S. O. Jaeschke, Chem.–Eur. J.,
2017, 23, 10838–10847; (b) J. Hain and G. Despras, Chem.
Commun., 2018, 54, 8563–8566.
Chem. Soc., 1989, 111, 6881–6882.
33 O-Methylated DHAB derivatives could not be isolated aer
glycosylation as they were always obtained as mixtures
with the corresponding glycosylated products. To conrm
DHAB O-methylation, both the mono- and di-O-methylated
derivatives were independently prepared and their NMR
and TLC characteristics analysed (cf. ESI†). These data
allowed us to conrm their structure as byproducts formed
during the glycosylations.
´
21 (a) C. Lin, S. Maisonneuve, R. Metivier and J. Xie, Chem.–Eur.
J., 2017, 23, 14996–15001; (b) C. Lin, S. Maisonneuve,
C. Theulier and J. Xie, Eur. J. Org. Chem., 2019, 1770–1777.
22 V.
Chandrasekaran,
E.
Johannes,
H.
Kobarg,
¨
F. D. Sonnichsen and T. K. Lindhorst, ChemistryOpen, 34 M. C. Galan, C. Brunet and M. Fuensanta, Tetrahedron Lett.,
2014, 3, 99–108. 2009, 50, 442–445.
23 (a) N. Kurita, S. Nebashi and M. Kojima, Chem. Phys. Lett., 35 D. Crich and M. Smith, J. Am. Chem. Soc., 2001, 123, 9015–
´
2005, 408, 197–204; (b) G. Gabor, Y. F. Freı and E. Fischer,
9020.
J. Phys. Chem. A, 1968, 72, 3266–3272.
24 M. Bols and C. M. Pedersen, Beilstein J. Org. Chem., 2017, 13,
93–105.
36 S. Sattin, M. Panza, F. Vasile, F. Berni, G. Goti, J. Tao,
E. Moroni, D. Agard, G. Colombo and A. Bernardi, Eur. J.
Org. Chem., 2016, 3349–3364.
25 B. Lal, B. N. Pramanik, M. S. Manhas and A. K. Bose, 37 H.-M. Chen and S. G. Withers, Carbohydr. Res., 2018, 467,
Tetrahedron Lett., 1977, 23, 1977–1980.
33–44.
This journal is © The Royal Society of Chemistry 2020
RSC Adv., 2020, 10, 17432–17437 | 17437