8-hydroxyquinoline glycoconjugates: Modifications in the linker structure and their effect on the cytotoxicity of the obtained compounds

Article abstract of DOI:10.3390/molecules24224181

Small molecule nitrogen heterocycles are very important structures, widely used in the design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained. In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position, using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition of β-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression. All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration range. The presence of additional amide groups in the linker structure improves the activity of glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers. The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of chelating copper ions, which increases their anti-cancer potential.

Full text of DOI:10.3390/molecules24224181

molecules
Article
8-Hydroxyquinoline Glycoconjugates: Modifications
in the Linker Structure and Their Effect on the
Cytotoxicity of the Obtained Compounds
Monika Krawczyk 1,2,
*
, Gabriela Pastuch-Gawołek 1,2 , Aleksandra Pluta 1, Karol Erfurt 3,
Adrian Domin´ski 4 and Piotr Kurcok 4
1
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Silesian University of
Technology, B. Krzywoustego 4, 44-100 Gliwice, Poland; gabriela.pastuch@polsl.pl (G.P.-G.);
aleksandrapluta93@o2.pl (A.P.)
Biotechnology Centre, Silesian University of Technology, B. Krzywoustego 8, 44-100 Gliwice, Poland
2
3
Department of Chemical Organic Technology and Petrochemistry, Silesian University of Technology,
B. Krzywoustego 4, 44-100 Gliwice, Poland; karol.erfurt@polsl.pl
Centre of Polymer and Carbon Materials, Polish Academy of Sciences, M. Curie-Sklodowskiej 34,
4
41-819 Zabrze, Poland; adrian.dominski@cmpw-pan.edu.pl (A.D.); piotr.kurcok@cmpw-pan.edu.pl (P.K.)
*
Correspondence: monika.krawczyk@polsl.pl; Tel.: +48-32-237-1759
Academic Editor: Robert Musioł
Received: 31 October 2019; Accepted: 15 November 2019; Published: 18 November 2019
ꢀꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀꢁꢂꢃꢄꢅꢆ
Abstract: Small molecule nitrogen heterocycles are very important structures, widely used in the
design of potential pharmaceuticals. Particularly, derivatives of 8-hydroxyquinoline (8-HQ) are
successfully used to design promising anti-cancer agents. Conjugating 8-HQ derivatives with
sugar derivatives, molecules with better bioavailability, selectivity, and solubility are obtained.
In this study, 8-HQ derivatives were functionalized at the 8-OH position and connected with sugar
derivatives (D-glucose or D-galactose) substituted with different groups at the anomeric position,
using copper(I)-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC). Glycoconjugates were
tested for inhibition of the proliferation of cancer cell lines (HCT 116 and MCF-7) and inhibition
of β-1,4-galactosyltransferase activity, which overexpression is associated with cancer progression.
All glycoconjugates in protected form have a cytotoxic effect on cancer cells in the tested concentration
range. The presence of additional amide groups in the linker structure improves the activity of
glycoconjugates, probably due to the ability to chelate metal ions present in many types of cancers.
The study of metal complexing properties confirmed that the obtained glycoconjugates are capable of
chelating copper ions, which increases their anti-cancer potential.
Keywords: quinoline; glycoconjugates; click reaction; 1,3-dipolar cycloaddition; chelators; anticancer
properties
1. Introduction
Cancer is one of the biggest problems in modern medicine and one of the main causes of death in
the world. The high toxicity of drugs and the growing resistance of cancer cells to a significant number
of pharmaceuticals increasingly limit the possibility of obtaining successful results of anti-cancer therapy.
Therefore, it is necessary to search for new, effective chemotherapeutics characterized by low toxicity
and high selectivity profile. Analysis of the Food and Drug Administration (FDA) database revealed
that of the novel approved drugs for oncology in 2018, 7 are biologicals and 13 are small-molecules
drugs. Importantly, all of the newly reported chemotherapeutics contain an N-heterocyclic fragment in
their structure [1]. Small molecule nitrogen heterocycles are very important structures, widely used
Molecules 2019, 24, 4181; doi:10.3390/molecules24224181
www.mdpi.com/journal/molecules

Molecules 2019, 24, 4181
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in the design of potential pharmaceuticals for several years [2]. Among them, the quinoline scaffold,
which is present in many classes of biologically active compounds, deserves special attention [3–6].
The quinoline scaffold is often used as a privileged structure in the design of a large number of
structurally diverse molecules that exhibit promising pharmacological effects. Particularly, derivatives
of 8-hydroxyquinoline (8-HQ) are successfully applied to design chemotherapeutics used in the treatment
of bacterial [7–9], fungal [10,11] and neurodegenerative diseases [12,13]. An important element of
8-HQ biological activity is the ability to chelate metal ions, which makes 8-HQ a promising anti-cancer
agent [14–16].
Transition metal ions, including Fe2+, Cu2+, and Zn2+ play a significant role in the human organism.
They affect the proper course of many key cellular processes. Therefore, it is important to maintain
homeostasis. Incorrect metabolism of the above microelements may contribute to the development of
many diseases [17,18]. There are several strategies for controlling the proper level of metals within cells
and tissues. For this purpose, a common strategy is the use of chelators or ionophores. Chelating agents
are successfully used to remove excess metal ions from the body. Whereas, ionophores are used to
transport metal ions via cell membrane in both directions [18,19]. Copper is one of the transition metals
which complex compounds have been intensively studied in recent years for anticancer applications.
As is well known, copper is an essential cofactor for cancer growth and angiogenesis. Numerous
studies have shown that an elevated level of copper is directly correlated with cancer progression.
Additionally, copper concentration correlated with the age of patients and the stage of cancer [20
Excess of copper ions was found in the serum and tissues of patients with, among others: breast [24
prostate [26
observations suggest that copper ions may be one of the selective targets for cancer treatment [20
–
24].
,
25],
,
27], colorectal [28], lung [29] and brain [30] cancers, compared to healthy people. These
,
31–33].
Among the known copper chelators include tetrathiomolybdate, trientine, and D-penicillamine
primarily used to treat Wilson0s disease [34]. Clinical studies have shown that these compounds are
effective in inhibiting the angiogenesis of some types of cancer [35–41]. The literature also reports on
the use of 8-HQ derivatives as copper chelators. Due to the presence of free electron pairs on nitrogen
and oxygen atoms of 8-HQ, they have the ability to complex Cu2+ ions, forming chelates, which are
then removed from the body [14–16,42,43]. However, metal ions play an important role in many
cellular processes, including those necessary for the proper functioning of the organism. Therefore,
traditional chelators can cause a deficiency of copper in healthy tissues. The consequence of the lack
of selectivity in directing drugs to a specific site of action may be undesirable side effects resulting
from the implemented anticancer therapy. That is why the aim of many researchers is to develop more
selective and safer drugs. Therefore, an ideal anti-cancer drug should be selective for cancer cells,
thereby alleviating the undesirable toxic effects of chemotherapy.
During designing new drugs, it is very important to know and use the differences between
cancer cells and healthy cells. One such difference is the specific metabolism of glucose in cancer cells.
It has been proven that cancer cells have an increased demand for glucose compared to healthy cells,
which metabolizes it to obtain the energy needed to increase proliferation. This provides the cells
with a sufficient amount of nutrients and energy to carry out the processes taking place during the
cell cycle. This phenomenon is known as the Warburg effect and arises from mitochondrial metabolic
changes. It consists in the fact that cancer cells produce their energy through glycolysis followed
by lactic acid fermentation, characteristic of hypoxic conditions, and its level is much higher (more
than a hundred times) than in healthy cells, for which the main source of energy is mitochondrial
oxidative phosphorylation [44
overexpression of GLUT transporters. There are special proteins that mediate the transfer of sugars
across cell membranes [46 48]. Therefore, sugars are an attractive system for transporting drugs
,45]. Increased glycolysis process in cancer cells is associated with the
–
directly to cancer cells. The strategy of conjugating sugar derivatives with biological active aglycons
is widely used in research on the synthesis of new drugs, supporting the treatment against various
diseases [49]. The chelating functions of glycoconjugates are masked by the presence of a sugar unit
until the release of active aglycon in the target cells, occurring as a result of hydrolysis catalyzed by

Molecules 2019, 24, 4181
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specific β-glycosidases [50]. Consequently, drug interference in the glycolytic pathway should be
effective and more selective for cancer cells.
As a result of conjugating 8-HQ derivatives with sugar derivatives, a molecule with better
bioavailability, selectivity and solubility can be obtained [50–53]. Considering the potential therapeutic
application of planned connections, this synthesis must be simple, fast, selective and efficient.
An example of a reaction that meets these criteria is the reaction of 1,3-dipolar azide-alkyne cycloaddition,
which leads to receiving the 1,2,3-triazole ring between joined compounds.
We have recently shown that the 1,2,3-triazole ring is an important element for glycoconjugate
activity [54] (Figure 1). Except for the role of a connection between two active groups, it also has other
interesting properties. The H-C(5) atom in the triazole ring is a donor for a hydrogen bond, while
the free electron pair at the N(3) atom in the triazole can be used as an acceptor in the formation of a
hydrogen bond. Their tendency to form hydrogen bonds increases the solubility of such molecules,
which favor binding to biomolecular targets [55]. The aim of present work is to extend the library
of such combinations. The general structure of the planned glycoconjugates is shown in Figure 2.
It was decided to reverse the direction of linking reactive moieties compared to the previously reported
glycoconjugates [54], consisting of sugar azides and propargyl derivatives of 8-HQ (Figure 1) and
see how this will affect the activity of glycoconjugates. In addition, it was decided to check how the
structure modification of the linker of the quinoline glycoconjugates affects their biological properties.
It was assumed that an extension of the alkyl chain between the triazole ring and quinoline or sugar part
should increase the “flexibility” of the obtained compounds, which may affect the cytotoxicity profile of
the molecules. Moreover, insertion into a linker an additional amide or carbamate bonds, the presence
of which is observed in many biologically active compounds should improve glycoconjugates chelating
ability [56]. Therefore, it was decided to check whether the addition of this structural element to
quinoline glycoconjugates will improve their activity compared to previously obtained derivatives.
Figure 1. Structures of previously obtained glycoconjugates [54].
Figure 2. General structure of the glycoconjugates presented in this paper.
A multiplicity of structural modifications in building blocks for the synthesis of glycoconjugates
and their combination in various configurations will allow determining the relationships between
the chemical structure of this group of compounds and their biological activity. This will allow also
identifying those specific structural elements that are responsible for demonstrating biological activity.
This is important information from the point of view of the mechanisms of action of designed structures.
2. Results and Discussion
2.1. Synthesis
As mentioned above, the synthetic aim of this work was to create a large library of compounds based
on the 8-HQ scaffold with a sugar fragment attached via an appropriate linker. Target glycoconjugates

Molecules 2019, 24, 4181
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were obtained by modifying commercially available 8-hydroxyquinoline
1 or 8-hydroxyquinaldine 2,
and then connecting them with derivatives of D-glucose or D-galactose substituted with different groups
at the anomeric position. A common feature of all glycoconjugates is the presence of a 1,2,3-triazole
ring in the linker structure. This improves their cytotoxic activity, probably by increasing the ability to
metal ions chelation found in many types of cancers [54,55]. In addition, the used substrates have a
relatively small size and are easy to modify, which makes them particularly interesting from the point
of view of using them to design potential drugs.
The first part of the synthesis concerned the preparation of the corresponding quinoline derivatives
functionalized in the 8-OH position with propargyl or azide groups, that are involved in the click
chemistry reaction. The path of the syntheses is presented in Scheme 1.
Cl-
ii
N+
5a-10a
R
O
n = 1-3
i
N
R
N
R
O
OH
5: R=H, n=2 (82%)
6: R=H, n=3 (75%)
7: R=H, n=4 (76%)
8: R=CH3, n=2 (83%)
9: R=CH3, n=3 (71%)
10: R=CH3, n=4 (69%)
1: R=H
2: R=CH3
N
R
3: R=H (88%)
4: R=CH3 (73%)
O
iii
n = 2-4
N3
Scheme 1. Synthesis of 8-hydroxyquinoline derivatives 3–10. Reagents and Conditions: (i) propargyl
bromide, K2CO3, acetone, r.t., 24 h; (ii) 1. 2-bromoethanol or 3-bromo-1-propanol or 4-bromo-1-butanol,
K2CO3, acetone, r.t., 24 h; 2. methanesulfonyl chloride or p-toluenesulfonyl chloride, Et3N, CH2Cl2;
r.t., 3h; 3. NaN3, DMF, r.t., 24 h; (iii) 1-azido-2-bromoethane or 1-azido-3-bromopropane or 1-azido-
4-bromobutane, K2CO3, acetone, 50 ◦C-r.t., 24 h.
Propargyl quinoline derivatives
according to the previously published procedure [54
reacted with propargyl bromide in a reaction carried out under basic conditions. The first approach
to the synthesis of 8-(2-azidoethoxy)quinolone was the reaction of 8-HQ with 2-bromoethanol
3
or
4
were obtained in good yields (88% and 73% respectively),
,
57]. The corresponding compound or was
1
2
5
1
to obtain 8-(2-hydroxyethoxy)quinoline. The obtained alcohol was treated with methanesulfonyl
or p-toluenesulfonyl chloride in the presence of a non-nucleophilic base (TEA) followed by sodium
azide in DMF. However, the formation of the expected product
5 was no observed. Also in case of
lengthening the alkyl chain of the donor, the desired products 6–10 could not be obtained. Treatment of
8-(2-hydroxyethoxy)quinoline by azidotrimethylsilane (TMSN3) in the presence of Lewis acid also did
not give the expected products. The application of the Appel reaction conditions, in which the alcohol
reacts with carbon tetrachloride in the presence of triphenylphosphine also not allowed to obtain the
desired products. Instead, spectroscopic data (HRMS) confirmed the formation of a resonance-stabilized
structure of the tricyclic oxazaquinolinium salts 5a–10a
[58]. Finally, to obtain compounds 5–10,
a reaction of quinoline derivatives or with 1-azido-2-bromoethane, 1-azido-3-bromopropane or
1
2
1-azido-4-bromobutane as donors of desired groups was carried out. These donors were previously
obtained by monoazidation of the corresponding dibromoalkane with NaN3 in DMF [59]. The optimal
yield of the desired products was obtained by carrying out the reaction at 50 ◦C, using an equimolar
ratio of substrates. Except for the monosubstituted derivatives (50% yields), diazidesubstituted
derivatives (25% yield) were also obtained (the yield was estimated by 1H NMR).
Sugar derivatives substituted at the anomeric position were a second necessary structural element
for the synthesis of glycoconjugates. The synthesis route to the corresponding protected and deprotected
derivatives of D-glucose and D-galactose are shown in Schemes 2–4. The choice of sugar units is
dictated by the frequency of their occurrence and their importance for cell metabolism. The procedure

Molecules 2019, 24, 4181
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for obtaining 2,3,4,6-tetra-O-acetyl-
β-d-glycopyranosyl amines 19 and 20 has been described in detail
in earlier works [51,54,60] (Scheme 2).
R2
R2
R1
HO
R2
R2
R2
OAc
OAc
OH
OAc
OAc
O
R1
i
ii
iii
iv
R1
R1
O
O
O
O
R1
OAc
AcO
N3
NH2
AcO
AcO
AcO
OH
OAc
OH
OAc
OAc
OAc
Br
1
2
1
2
1
2
1
2
1
2
11
12
13
14
15
16
17
18
19
20
: R =OH, R =H
: R =OAc, R =H (96%)
: R =OAc, R =H (91%)
: R =OAc, R =H (90%)
: R =OAc, R =H (100%)
1
2
1
2
1
2
1
2
1
2
: R =H, R =OH
: R =H, R =OAc (81%)
: R =H, R =OAc (90%)
: R =H, R =OAc (85%)
: R =H, R =OAc (100%)
Scheme 2. Synthesis of sugar derivatives 13
–
20. Reagents and Conditions: (i) CH3COONa, Ac2O, b.p.,
1 h; (ii) CH3COOH, 33% HBr/AcOH, r.t. 1 h; (iii) NaN3, TBASH, CHCl3/NaHCO3, r.t. 2 h; (iv) 20%
Pd(OH)2/C, THF:EtOH (2:1, v/v), H2, 1.5 bar, 2 h.
Scheme 3. Synthesis of sugar derivatives 21
–
30. Reagents and Conditions: (
i
) propargyl alcohol, BF3 Et2O,
·
DCM, r.t., 1 h; (ii) 2-bromoethanol, BF3·Et2O, DCM, r.t., 2 h; (iii) NaN3, DMF, r.t. 24 h; (iv) 1. MeONa,
MeOH, r.t. 20 min; 2. Amberlyst-15.
Scheme 4. Synthesis of sugar derivatives 31–44. Reagents and Conditions: (i) chloroacetyl chloride,
TEA, DCM, r.t., 1 h; (ii) NaN3, DMF, r.t. 24 h; (iii) Propiolic acid, DCC, DCM, r.t. 2 h; (iv) propargyl
chloroformate, Hünig0s base, DCM, r.t. 2 h; (v) 1. MeONa, MeOH, r.t. 20 min; 2. Amberlyst-15.
Sugar derivatives in which the alkynyl or azide moiety was introduced by the formation of an
O-glycosidic linkage were prepared by reacting per-O-acetylated D-glucose 13 or D-galactose 14 with

Molecules 2019, 24, 4181
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propargyl alcohol or 2-bromoethanol in the presence of a Lewis acid as a catalyst (Scheme 3) [61,62].
The reactions were carried out in an anhydrous DCM in the presence of boron trifluoride etherate
until the complete conversion of the substrate, which was monitored by TLC. The reaction mixture
was diluted with dichloromethane and extracted with NaHCO3 and brine to wash off the acid.
The acetyl neighboring-group participation at the C-2 position of the sugar ensured the formation of
an intermediate acyloxonium ion, which for steric reasons could be “attacked” by a nucleophile only
from the opposite side, resulting in only products of the
large coupling constant from the H-1 proton equal J = 8.0 Hz observed in the 1H NMR spectra for
compounds 21 22 and 25 26. As a result, propargyl 2,3,4,6-tetra-O-acetyl- -D-glycopyranosides
21 and 22 were obtained in good yields (89% and 83% respectively), whereas 2-bromoethyl
2,3,4,6-tetra-O-acetyl- -D-glycopyranosides 25 and 26 were obtained in slightly lower yields (76% and
71% respectively). 2-Azidoethyl 2,3,4,6-tetra-O-acetyl- -D-glycopyranosides 27 and 28 were obtained
β-configuration. This is confirmed by the
–
–
β
β
β
by substituting bromine by sodium azide in the reaction carried out in DMF in almost quantitative
yield. Confirmation of bromine exchange to the azide moiety was the appearance in the 13C NMR
spectra of the signal of CH2N3 carbon with a shift of about
δ = 50.55 ppm for 27 and 50.60 ppm for 28,
while the signal of CH2Br carbon was observed at about δ = 29.83 ppm for 25 and 29.91 ppm for 26.
In the next step, sugar derivatives containing an amide or a carbamate moiety at the sugar
anomeric position were obtained by several-step synthesis presented in Scheme 4.
Derivatives of 2,3,4,6-tetra-O-acetyl-N-(β-D-glycopyranosyl)azidoacetamide 33, 34 were obtained
in two-steps procedure. 1-Aminosugars 19 or 20 were reacted with chloroacetyl chloride in the presence
of TEA, which neutralized the formed of hydrogen chloride. This approach eliminates the use of
toxic SnCl4 and tin metal to reduce glycopyranosyl azides, which has been described as a method for
the synthesis of N-glycopyranosyl chloroacetamides [63]. In the second step, the terminal chlorine
atom in compounds 31 and 32 was exchanged with an azide group by a nucleophilic substitution
reaction with sodium azide in dry DMF. The structures of the obtained products were confirmed on
the basis of NMR spectra analysis. In this case, the characteristic carbon signal of CH2N3 located at
δ = 52.59 ppm for 33 and 52.61 ppm for 34 in 13C NMR spectra was shifted from
42.26 ppm corresponding to chloroacetamide derivatives 31 and 32.
δ = 42.25 ppm and
In turns, structures 37 and 38 were obtained in the reaction of 1-amino sugars 19 or 20 with
propargylic acid. In these reactions activating the non-reactive carboxyl group seems to be necessary.
Of the many ways to form an amide bond, initially, it was decided to use the method developed
by Kaminski and co-workers [64]. This method involves creating so-called superactive ester 4-(4,6-
dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) in situ in reaction between
2-chloro-4,6-disubstituted-1,3,5-triazines (CDMT) and N-methylmorpholine (NMM). It turned out that
as a result of this reaction, only traces of expected products were formed. In the next approach,
the carbodiimide method was used to the condensation reaction using DCC as a coupling agent [65].
The reaction was carried out in DCM in which the isolated DCU is insoluble and could be separated from
the reaction mixture by filtration. As a result, 2,3,4,6-tetra-O-acetyl-N-(β-d-glycopyranosyl)propiolamides
37 and 38 were obtained in high yields (90% and 77% respectively).
In order to obtain sugar derivatives containing a carbamate group at the sugar anomeric position,
reactions of 1-amino sugars 19 and 20 with propargyl chloroformate, which is a reactive acylating agent,
were also carried out. This reaction requires the presence of a tertiary amine in the reaction medium
to entrap the formed HCl and avoid conversion of the amine into its non-reactive hydrochloride
salt [66]. However, the use of TEA gave only moderate yield, while the replacement of TEA with
N,N-diisopropylethylamine allowed obtaining the desired products 41 and 42 in high yields (81% and
88% respectively).
The ester type protecting groups in the sugar part increase the lipophilicity of glycoconjugates
and improved its passive transport inside the cell, where are enzymes capable of hydrolyzing them.
However, for some biological studies, it is also necessary to use compounds with unprotected hydroxyl
groups. The removal of the acetyl protecting groups from sugars was carried out according to the classic

Molecules 2019, 24, 4181
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Zemplén protocol under alkaline conditions using a solution of sodium methoxide in methanol (0.2
molar equiv.) [67]. The final step was to neutralize the reaction mixture with the use of Amberlyst-15
ion exchange resin, after which the mixture was filtered to give compounds 23, 24, 29, 30, 35, 36, 39, 40,
43, 44 sufficiently pure for further reactions.
For the preparation of glycoconjugates, the obtained protected or deprotected derivatives of
D-glucose or D-galactose were combined with derivatives of 8-HQ using copper(I)-catalyzed 1,3-dipolar
azide-alkyne cycloaddition (CuAAC) [68
shown in Scheme 5. The reactants were combined in an equimolar ratio in a THF/i-PrOH/H2O solvent
system at room temperature. As the source of copper ions, CuSO4 5H2O was used. Whereas, sodium
,69]. A general scheme for the synthesis of glycoconjugates is
·
ascorbate (NaAsc) was a reducing agent for Cu ions from II for the I oxidation stage. Due to the
using Cu(I) as a catalyst, the reaction was carried out at room temperature and only 1,4-disubstituted
1,2,3-triazoles were obtained. It is worth noting that both protected and deprotected sugar derivatives
can be used for this reaction. This eliminates the need for a final deprotection of glycoconjugates, which
could adversely affect the yields of the unprotected products. The crude products of these reactions were
purified by column chromatography. As a result of the CuAAC reaction, glycoconjugates 45–108 were
obtained with the yields shown in the Tables 1–5. The structure of substrates for CuAAC reactions and
all obtained glycoconjugates were confirmed by 1H and 13C NMR spectroscopy. For glycoconjugates,
HRMS analyses were also performed. All these data are included in the Supplementary Materials.
The physicochemical properties, such as melting point and optical rotation, were also determined.
Scheme 5. General scheme for the synthesis of glycoconjugates 45
(i) CuSO4·5H2O, NaAsc, i-PrOH, THF, H2O, r.t., 24 h.
–108. Reagents and Conditions:
2.2. Biological Studies
2.2.1. Cytotoxicity Evaluation of Glycoconjugates
Glycoconjugates have been tested for their potential anticancer activity in vitro. For this purpose,
the whole range of obtained glycoconjugates and substrates used for their synthesis were subjected to
a cytotoxicity screening using MTT assay on cell lines: HCT 116 (colorectal carcinoma cell line) and
MCF-7 (human breast adenocarcinoma cell line). In these lines, overexpression of the glucose and
galactose transporters was observed [49,70–73]. For compounds presenting the highest antiproliferative
activity within the cancer cell line, cytotoxicity tests on Normal Human Dermal Fibroblast-Neonatal
cells (NHDF-Neo) were also be performed, to determine their selectivity index. Tests were conducted
for glycoconjugates solutions at concentrations ranging from 0.01 mM to 0.8 mM. The determined
IC50 values, defined as 50% cell growth inhibition compared to the untreated control, are shown in
Tables 6 and 7). The effect of the length and structure of the linker connecting quinoline with the sugar
fragment for the activity of glycoconjugates was investigated.

Molecules 2019, 24, 4181
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Table 1. Yields of glycoconjugates 45–68.
General
Structure
Product
R1
R2
R3
R4
n
8-HQ Derivative Sugar Derivative
Yield [%]
45
46
47
48
49
50
51
52
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
5
5
8
8
5
5
8
8
21
22
21
22
23
24
23
24
73
74
100
71
95
67
88
78
2
53
54
55
56
57
58
59
60
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
6
6
9
9
6
6
9
9
21
22
21
22
23
24
23
24
100
100
65
77
100
76
3
4
87
65
61
62
63
64
65
66
67
68
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
7
7
10
10
7
7
10
10
21
22
21
22
23
24
23
24
96
93
92
100
72
90
76
66
Table 2. Yields of glycoconjugates 69–76.
General
Structure
Product
R1
R2
R3
R4
8-HQ Derivative
Sugar Derivative
Yield [%]
69
70
71
72
73
74
75
76
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
3
3
4
4
3
3
4
4
27
28
27
28
29
30
29
30
78
62
97
77
62
55
58
59

Molecules 2019, 24, 4181
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Table 3. Yields of glycoconjugates 77–84.
General
Structure
Product
R1
R2
R3
R4
8-HQ Derivative
Sugar Derivative
Yield [%]
77
78
79
80
81
82
83
84
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
3
3
4
4
3
3
4
4
33
34
33
34
35
36
35
36
67
74
81
78
60
58
61
78
Table 4. Yields of glycoconjugates 85–100.
General
Structure
Product
R1
R2
R3
R4
n
8-HQ Derivative
Sugar Derivative
Yield [%]
85
86
87
88
89
90
91
92
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
5
5
8
8
5
5
8
8
37
38
37
38
39
40
39
40
85
86
87
88
89
90
91
92
2
93
94
95
96
97
98
99
100
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
6
6
9
9
6
6
9
9
37
38
37
38
39
40
39
40
93
94
95
96
97
98
99
100
3
Table 5. Yields of glycoconjugates 101–108.
General
Structure
Product
R1
R2
R3
R4
8-HQ Derivative
Sugar Derivative
Yield [%]
101
102
103
104
105
106
107
108
Ac
Ac
Ac
Ac
H
H
H
H
OAc
H
OAc
H
OH
H
OH
H
H
OAc
H
OAc
H
OH
H
OH
H
H
CH3
CH3
H
H
CH3
CH3
6
6
9
9
6
6
9
9
41
42
41
42
43
44
43
44
94
90
68
64
83
82
80
78

Molecules 2019, 24, 4181
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Table 6. Screening of cytotoxicity of substrates 1–10 used for glycoconjugation.
Activity IC50 [µM] a
Compound
MCF-7 c
HCT 116 b
NHDF-Neo b
1
2
3
4
5
6
7
8
>800
>800
>800
0.24 ± 0.01
43.18 ± 1.78
95.95 ± 4.29
223.63 ± 8.06
27.27 ± 0.06
244.44 ± 1.34
67.18 ± 3.49
633.02 ± 6.39
166.70 ± 7.15
114.72 ± 1.23
0.70 ± 0.01
>800
346.77 ± 2.23
>800
>800
>800
83.02 ± 1.83
461.39 ± 1.34
237.48 ± 2.11
>800
295.51 ± 7.37
196.47 ± 7.38
5.60 ± 0.10
26.60 ± 0.60
-
37.71 ± 0.94
-
188.14 ± 2.47
168.14 ± 1.13
>20
9
10
Doxorubicin
Cytotoxic was evaluated using the MTT assay; b Incubation time 24 h; c Incubation time 72 h.
a
Table 7. Screening of cytotoxicity of glycoconjugates derivatives of 8-hydroxyquinoline 45–108.
Activity IC50 [µM] a
Activity IC50 [µM] a
Compound
Compound
MCF-7 c
MCF-7 c
HCT 116 b
NHDF-Neo b
HCT 116 b
NHDF-Neo b
45
46
47
48
53
54
55
56
61
62
63
64
69
70
71
72
77
78
79
80
85
86
87
88
93
94
95
96
101
102
103
104
217.0 ± 4.7
248.8 ± 7.1
229.6 ± 2.6
257.1 ± 7.2
143.0 ± 2.3
168.9 ± 1.0
135.1 ± 7.0
244.8 ± 4.7
328.8 ± 9.0
389.5 ± 4.9
294.7 ± 1.8
499.8 ± 2.7
240.0 ± 2.3
280.9 ± 8.9
290.6 ± 7.0
763.3 ± 5.4
246.2 ± 6.2
119.1 ± 5.6
142.9 ± 2.9
519.2 ± 7.2
239.1 ± 3.0
270.6 ± 7.5
379.8 ± 1.4
272.3 ± 1.2
137.3 ± 2.1
229.8 ± 4.7
217.1 ± 1.5
249.2 ± 5.5
246.2 ± 1.3
369.0 ± 4.7
295.2 ± 8.2
515.7 ± 4.3
196.5 ± 1.9
196.5 ± 3.1
375.6 ± 8.3
231.8 ± 9.6
200.6 ± 1.1
190.4 ± 3.0
221.1 ± 2.4
240.2 ± 3.8
254.8 ± 3.6
233.1 ± 5.8
214.8 ± 1.7
241.9 ± 2.8
105.9 ± 4.1
217.9 ± 5.2
136.0 ± 1.5
317.8 ± 8.5
192.7 ± 3.7
39.1 ± 0.9
405.9 ± 5.7
49
50
51
52
57
58
59
60
65
66
67
68
73
74
75
76
81
82
83
84
89
90
91
92
97
98
99
100
105
106
107
108
>800
>800
>800
>800
>800
>800
>800
>800
>800
>800
>800
>800
>800
>800
>800
605.2 ± 1.3
320.2 ± 4.9
788.8 ± 7.5
>800
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
262.4 ± 1.7
-
-
214.8 ± 6.4
213.1 ± 3.0
426.8 ± 3.8
-
-
-
382.4 ± 2.1
>800
>800
-
>800
>800
>800
>800
>800
>800
>800
216.1 ± 9.7
220.0 ± 2.5
715.2 ± 9.6
-
219.1 ± 2.4
103.6 ± 2.5
480.8 ± 4.4
-
426.1 ± 1.3
>800
>800
>800
112.8 ± 1.6
194.4 ± 0.6
>800
>800
>800
87.9 ± 4.1
384.7 ± 8.3
>800
>800
>800
94.7 ± 0.5
166.3 ± 5.8
226.6 ± 4.0
301.0 ± 4.4
203.8 ± 3.6
129.7 ± 1.8
211.9 ± 1.1
178.9 ± 6.8
95.7 ± 0.02
256.0 ± 9.6
781.2 ± 3.5
297.9 ± 2.1
176.4 ± 1.8
203.6 ± 4.9
177.6 ± 2.6
223.4 ± 8.6
-
-
-
-
-
-
-
-
-
-
-
-
-
-
382.6 ± 2.4
>800
690.3 ± 4.0
629.0 ± 1.2
>800
>800
>800
>800
>800
>800
113.4 ± 0.9
677.9 ± 2.8
702.6 ± 1.9
-
>800
>800
163.1 ± 1.1
-
>800
>800
>800
>800
595.9 ± 9.0
>800
696,7 ± 1.6
436.3 ± 3.1
-
>800
586.0 ± 5.6
-
630.2 ± 2.7
>800
>800
>800
Cytotoxic was evaluated using the MTT assay; b Incubation time 24 h; c Incubation time 72 h.
a
As part of the experiments, it was checked whether the building blocks necessary to obtain final
glycoconjugates are able to limit the proliferation of cancer cells (Table 6). Sugar derivatives appeared
to be inactive on the tested cell lines. However, the high toxicity of parent compounds
1 and 2 towards
the MCF-7 cancer cell line was observed. A lower IC50 value was determined for 8-HQ than for
doxorubicin commonly used in cancer treatment. This observation indicates the huge sensitivity of
this particular cancer cell line to 8-HQ and gives hope for even more effective therapeutics based
on the 8-HQ scaffold. In addition, some of the derivatives of 8-HQ 5–10 were toxic to the tested

Molecules 2019, 24, 4181
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cell lines. However, further experiments have shown that they also cause the death of healthy cells.
Therefore, the next studies checked whether the addition of the sugar moiety to aglycon would affect
the selectivity of the obtained glycoconjugates.
The results of the cytotoxicity assay indicate that the glycoconjugates with a deprotected sugar
unit (right part of Table 7) are mostly unable to inhibit cell proliferation in the tested concentration
range. This is probably related to their hindered penetration into the cell through the lipid biological
barriers, due to the high hydrophilicity of the compounds, compared to glycoconjugates having acetyl
protecting groups. The exception is compound 81, whose IC50 = 112.8
±
1.6 µM for HCT 116 and 87.9
±
4.1 M for MCF-7. For its protected analog 77, the IC50 value twice as high was determined for both
µ
tumor cell lines. Most likely, in this case, GLUT transporters had a more important role in transporting
into the cell, and passive transport is less important. Unfortunately, this compound is also toxic to
healthy cells, so it cannot be considered a selective drug.
All glycoconjugates containing ester protection of hydroxyl groups in the sugar part proved
to be active on the tested cancer cell lines in the tested concentration range (left part of Table 7).
Their non-polar nature should facilitate the process of crossing through phospholipid bilayer and
penetrating into the cell, where then intracellular hydrolytic enzymes are able to remove the acetyl
groups. In addition, as opposed to substrates, some of the obtained glycoconjugates showed low
cytotoxicity to NHDF-Neo cells, especially glycoconjugates 45
Moreover, for the HCT 116 cell line, all protected glycoconjugates exhibit higher antiproliferative
activity relative to aglycons and . This fact confirms the accuracy of the assumption that in this
, 46, 85, and 86 derived from quinoline 5.
1
2
case, the presence of the sugar fragment improves the distribution and absorption of the compound,
and thus its activity.
In the beginning, it was decided to check the effect of the length of the linker between the
1,2,3-triazole fragment and the derivative of 8-HQ for glycoconjugate activity (compounds 45
The lowest IC50 values were obtained for glycoconjugates 53 56, whose alkyl chain between triazole
and 8-HQ consisted of 3 carbon atoms. However, further elongation of the alkyl chain in the compounds
61 64 resulted in a decrease in the cytotoxic activity of glyconjugates. Therefore, no further chain
extension seems necessary. On the other hand, the alkyl chain extension between the 1,2,3-triazole
ring and the sugar moiety in compounds 69 72 did not significantly affect the antiproliferative activity
of glycoconjugates. Noteworthy is compound 71, which turned out to be more active than the
unconjugated quinoline derivative and for which the selectivity index, calculated as the ratio of the
–68).
–
–
–
4
IC50 value determined for healthy cells to the IC50 value determined for tumor cells, equal 5.3 for
MCF-7 lines and 2.5 for HCT 116 lines. This observation makes it interesting in the aspect of further,
more detailed studies involving different cell lines.
Glycoconjugates 77
be more active relative to the tested cancer cell lines. Among them, the most promising results were
obtained for compounds 78 and 93. For the MCF-7 cell line, the IC50 value equals 39.1 0.9 M and
95.7 0.02
M, respectively. However, for HCT 116 not much higher IC50 were noted: 119.1 ± 5.6 µM
and 137.3 2.1 M, respectively. Unfortunately, these compounds were also toxic to healthy cells,
–100 containing an additional amide bond in the linker structure proved to
±
µ
±
µ
±
µ
so they cannot be considered selective drugs. It was noted that compound with 8-HQ fragment usually
showed higher cytotoxicity compared to derivatives with 2Me8HQ unit, while the type of sugar moiety
did not significantly affect to the glycoconjugate activity. Importantly, compounds 86–88 did not
show any ability to inhibit the proliferation of healthy cells while having a moderate ability to inhibit
cancer cells.
Recently, an important role in drug design has been played by compounds containing a carbamate
moiety in the structure. Carbamates are usually more stable under enzymatic hydrolysis than the
corresponding esters and are generally more susceptible to hydrolysis than amides. Carbamate
prodrugs have been designed for selective hydrolysis by human carboxylesterases to release active
drugs [56,74]. It appeared that glycoconjugates 101 and 103, based on the D-glucose moiety, showed

Molecules 2019, 24, 4181
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low cytotoxicity to healthy cells while showing significant antiproliferative activity against cancer cells.
For these compounds, a selectivity index for the MCF-7 cell line was 3.9 and 3.3 respectively.
2.2.2. Inhibitory Activity Against β-1,4-GalT
Tested cancer cell lines are characterized by overexpression of the
β-1,4-galactosyltransferase
(β-1,4-GalT) [75]. This enzyme belongs to the group of glycosyltransferases (GTs). Due to a number of
important functions that GTs perform, among others: post-translational protein modifications and
synthesis of oligosaccharide chains, they are an important object of research on potential anticancer
drugs. A high rate of glycosylation is a common disorder of cancer cell metabolism, and the expression
of GTs can be associated with cancer progression. GTs are a group of metal-dependent enzymes,
therefore the presence of a species capable of binding divalent metal ions in the molecule of potential
inhibitor appears to be necessary to inhibit the activity of these enzymes [75,76]. It seems appropriate
to use glycoconjugates derivatives of 8-HQ to coordinate the metal ions present in the active centers of
many enzymes, and thus to inhibit their activity.
It was decided to evaluate the obtained glycoconjugates for their inhibitory activity against enzyme
from the glycosyltransferases group. Therefore, the experiments will be carried out using commercially
available metal-dependent β-1,4-GalT I from bovine milk. To evaluate the activity of tested compounds,
concentrations of substrate and product of the enzymatic reaction in the reaction mixtures was
determined by RP-HPLC method, which is a modification of the Vidal method [77]. This method uses
UDP-Gal, a natural β-1,4-GalT donor type substrate and (6-esculetinyl) β-D glucopyranoside (esculine)
as glycosyl fluorescent acceptor. The number of products formed in the reaction with the addition of
glycoconjugates as potential enzyme inhibitors was compared with the number of products in reactions
carried out under the same conditions without the addition of inhibitors (test reactions). Analyzes
were conducted in the linear range of the peak area from the product and substrate concentration.
Experiments were conducted for glycoconjugates solutions at concentrations ranging from 0.1 mM to
0.8 mM. For the most active compounds, IC50 values were designated. The results are presented in
Table 8.
Table 8. Bovine milk β-1,4-Galactosyltransferase I assay results.
Compound
Percentage of Inhibition at 0.8 mM [%]
IC50 [mM]
49
50
51
52
57
58
59
60
65
66
67
68
73
74
75
76
81
82
83
84
65 ± 0.27
10 ± 0.17
64 ± 0.23
8 ± 0.17
0.57
-
0.60
-
0.40
-
0.40
-
72 ± 0.03
2 ± 0.37
68 ± 0.25
6 ± 0.47
70 ± 0.19
8 ± 0.51
0.46
-
0.35
73 ± 0.03
4 ± 0.45
-
-
-
-
-
-
-
-
-
45 ± 0.17
14 ± 0.22
35 ± 0.06
7 ± 0.29
33 ± 0.29
17 ± 0.07
18 ± 0.25
14 ± 0.07
In this study, the influence of the alkyl chain length between the 1,2,3-triazole fragment and the
8-HQ derivative (49 52, 57 60, 65 68), as well as between the 1,2,3-triazole fragment and the sugar
–
–
–

Molecules 2019, 24, 4181
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unit (73
amide bond in the structure of the glycoconjugate linker (81
experience [54], only glycoconjugates with an unprotected sugar part were tested.
Experiments have shown that parent compounds and substrates 10 are not able to inhibit
–76) for enzyme inhibition was tested. In addition, the effect of the presence of an additional
–
84) was analyzed. Based on previous
1
,
2
3–
the enzyme, which may indicate that the sugar fragment is necessary to obtain inhibitory activity.
For glycoconjugates obtained as a result of CuAAC reactions between sugar derivatives containing a
propargyl moiety and quinoline derivatives containing an azide moiety, the results indicate that all
tested glycoconjugates derivatives of D-glucose showed higher activity compared to their analogs
containing the D-galactose unit. However, the type of 8-HQ derivative did not matter in this case.
Considering the effect of linker length between the 1,2,3-triazole fragment and the 8-HQ derivative,
it can be clearly stated that the extension of the alkyl chain increases the inhibition of
β-1,4-GalTI
by glycoconjugates. In this group of compounds (49 52, 57 60, 65 68), all glycoconjugates based on
–
–
–
D-glucose moiety showed the ability to inhibit the enzyme by over 50% compared to the test reaction.
However, for compound 67, having four carbon atoms in the alkyl linker, the lowest IC50 value was
determined (0.35 mM). It is probable, that an extension of the alkyl chain length between the triazole
ring and quinolone, increases the “flexibility” of the molecule, which may have a better fit into the
active center of the enzyme. Much lower ability to inhibition of the model enzyme was observed for
glycoconjugates that were obtained in the CuAAC reaction of sugar derivatives containing an azide
group and quinoline derivatives containing the propargyl moiety. Glycoconjugates with an ethoxy
fragment between the 1,2,3-triazole and sugar units (73
–
76) were not able to inhibit
β-1,4-GalTI by
50%. However, they showed slightly increased activity compared to glycoconjugates 81
–
84, containing
an additional amide fragment in the structure. The amide fragment is in close distance to the aromatic
moiety, which creates a high rigidity of the molecule and probably makes it difficult to fit into the
active center of the enzyme. Therefore, the addition of an amide fragment is not a good idea for the
design of β-1,4-GalT inhibitors.
2.3. Study of Metal Complexing Properties
Previously it was mentioned that cancer cells exhibit an increased concentration of copper
ions [20–24]. Moreover, it is broadly known that some quinoline derivatives possess metal ions
complexing properties [18] what is essential for their anti-proliferative properties [51]. Bivalent metal
ions are coordinated by phenol oxygen atom as well as nitrogen atom of 8-HQ ring with the formation
of an 8HQ-metal ion complex with stoichiometry 2:1 [78]. In addition, 1,2,3-triazole ring also has a
metal-complexation ability [79]. Therefore, it is interesting if the addition of linker containing such
fragment having metal ions chelation ability into 8-HQ might significantly increase the metal ion
complexation capability. The capability of complexes formation by investigated glycoconjugates
and stoichiometry of such complexes was evaluated for compounds 101 and 93 with copper ions by
spectroscopic titration experiments using UV-VIS. The UV-VIS spectrum of 101 is shown in Figure 3a.
The addition of subsequent copper ion portions to glycoconjugate solution results in a gradual lowering
of absorption bands at 242 nm and 310 nm. In addition, increase of the absorption band at 265 nm
was observed. Importantly, during titration two well-defined isosbestic points around 250 nm and
286 nm were noted indicating the glycoconjugate-copper ion complex formation. The stoichiometry of
obtained complexes was determined with Job0s plot using the changes in absorption band at 265 nm.
The plotted graph presenting the difference in absorbance,
∆
A = Ax
−
A0 as a function of molar fraction
[101]/[101 + Cu2+] was shown in Figure 3b. Maximum observed at molar fraction 0.5 in obtained curve
indicates a formation of 1:1 complex of glycoconjugate:copper ion, regardless of the type of linker (see
Supplementary Materials).
ESI-MS spectra showed that copper ions are complexed by investigated glycoconjugates. The ESI-MS
spectrum in positive ions mode of the investigated compound 101 (Figure 4a) revealed the presence
of the ion at m/z = 658.35 (adduct [101 + H]+) corresponding to protonated glycoconjugate molecule
and less intensive one corresponding to its sodium adduct, m/z = 680.36 [101 + Na]+. Additionally,

Molecules 2019, 24, 4181
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ions of 1012 aggregate (dimer) adducts can be noticed, respectively at m/z = 1314.23 [1012 + H]+,
1337.26 [1012 + Na]+ and 1353.19 [1012 + K]+. In the ESI-MS of glycoconjugate partially titrated with
copper ions (Figure 4b) the most abundant peak at m/z = 720.15 correspondings to [101 + Cu(I)]+
is visible. The second intensive signal m/z = 658.2 is derived from glycoconjugate still present in
the solution. Moreover the signals at m/z = 1377.17 and at m/z = 360.28 corresponding to dimer
1012 complex with Cu [1012 + Cu(I)]+ and complex [101 + Cu(II)]2+ were observed. The ESI-MS/MS
fragmentation spectrum of the ion with m/z = 1377.17 (see Supplementary Data) reveals only one peak
at m/z = 720 corresponding to complex [101 + Cu(I)]+. It confirms that ion at m/z = 1377.17 corresponds
to Cu+-dimer complex (1012 is present in the initial solution, see Figure 4a). Thus, complex with
apparent 2:1 stoichiometry is observed, but in fact, the complex is formed probably only with one of
the 101 molecules of the dimer. Moreover, in the signals ascribed to formed complexes characteristic
two peaks with the difference of 2 Da are observed. Such spectrum is typical of copper complexes due
to existence of copper in two basic isotopic forms (63Cu (69,17%) and 65Cu (30,83%)) [80]. It may seem
surprising that copper(I) complexes are observed in the ESI-MS spectrum since copper(II) was used for
titration. This phenomenon can be explained by a reduction reaction proceeding under the conditions
of the analysis as a result of charge transfer between the metal complexes and the solvent molecules in
the gas-phase [81–83].
Figure 3.
(a)—UV spectrum of compound 101 with the addition of copper sulfate pentahydrate in
methanol; (b)—Job0s plot of 101 with Cu2+. The absorbance was monitored at 265 nm.
Figure 4. Cont.

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Figure 4. ESI-MS (positive-ion mode) spectrum of (a) 101 compound and (b) 101 compound after
addition of Cu2+ ions into 101 solution.
3. Materials and Methods
3.1. General Information
NMR spectra were recorded with an Agilent spectrometer at a frequency of 400 MHz using TMS
or DSS as the internal standards and CDCl3, CD3OD, DMSO-d6 or D2O as the solvents. NMR solvents
were purchased from ACROS Organics (Geel, Belgium). Chemical shifts (δ) are expressed in ppm
and coupling constants (J) in Hz. The following abbreviations were used to explain the observed
multiplicities: s: singlet, d: doublet, dd: doublet of doublets, ddd: doublet of doublet of doublets,
t: triplet, dd-t: doublet of doublets resembling a triplet (with similar values of coupling constants), m:
multiplet, p: pentet (quintet), b: broad. High-resolution mass spectra (HRMS) were recorded with a
WATERS LCT Premier XE system using the electrospray-ionization (ESI) technique. Optical rotations
were measured with a JASCO P-2000 polarimeter using a sodium lamp (589.3 nm) at room temperature.
Melting point measurements were performed on OptiMelt (MPA 100) Stanford Research Systems.
Reactions were monitored by thin-layer chromatography (TLC) on precoated plates of silica gel 60 F254
(Merck Millipore, Burlington, MA, USA). The TLC plates were visualized under UV light (λ = 254 nm)
or by charring the plates after spraying with 10% solution of sulfuric acid in ethanol. Crude products
were purified using column chromatography performed on Silica Gel 60 (70–230 mesh, Fluka, St. Louis,
MI, USA), developed using toluene:EtOAc or CHCl3:MeOH as solvent systems. All evaporations were
performed on a rotary evaporator under diminished pressure at 40 ◦C. Reversed-phase HPLC analyses
were performed using JASCO LC 2000 apparatus equipped with a reverse-phase column (Nucleosil
100 C18.5
µ
m, 25
×
0.4 cm; mobile phase: H2O/MeCN 90:10, flow rate 0.8 mL/min) with a fluorescence
detector (FP). Fluorescence for substrate and product was read at 385 nm excitation/540 nm emission.
The absorbance on MTT assay was measured spectrophotometrically at the 570 nm wavelength using
a plate reader (Epoch, BioTek, USA).
All of the chemicals used in the experiments were purchased from Sigma- Aldrich, ACROS Organics,
Fluka and Avantor and were used without purification. 8- Hydroxyquinoline
1, 8-hydroxyquinaldine
2
, D-glucose 11 and D-galactose 12 are commercially available (Sigma-Aldrich). 8-(2-Propyn-1-
yloxy)quinoline
glucopyranose 13
-D-glucopyranosyl bromide 1
2,3,4,6-tetra-O-acetyl- -D-glucopyranosyl azide 1
3
[
[
57], 2-methyl-8-(2-propyn-1-yloxy)quinoline
54], 1,2,3,4,6-penta-O-acetyl- -D-galactopyranose 14
54], 2,3,4,6-tetra-O-acetyl-
4
[
57], 1,2,3,4,6-penta-O-acetyl-
β
-D-
β
[
54], 2,3,4,6-tetra-O-acetyl-
α
5
[
α
-D-galactopyranosyl bromide 16 [
54],
β
7
[54], 2,3,4,6-tetra-O-acetyl-
β-D-galactopyranosyl

Molecules 2019, 24, 4181
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azide 1
galactopyranosyl amine 20
propargyl 2,3,4,6-tetra-O-acetyl-
-D-glucopyranoside 25 62], 2-bromoethyl 2,3,4,6-tetra-O-acetyl-
azidoethyl 2,3,4,6-tetra-O-acetyl- -D-glucopyranoside 27 62], 2-azidoethyl 2,3,4,6-tetra-O-acetyl-
62], 2,3,4,6-tetra-O-acetyl-N-( -D-glucopyranosyl)propiolamide 37 65],
-D-galactopyranosyl)propiolamide 38 65], 2,3,4,6-tetra-O-acetyl-N-( -D-
66] and 2,3,4,6-tetra-O-acetyl-N-( -D-galactopyranosyl)-O-
66] were prepared according to the respective published procedures. Propargyl
-D-glucopyranoside 23, propargyl -D-galactopyranoside 24, 2-azidoethyl -D-glucopyranoside
-D-galactopyranoside 30, N-( -D-glucopyranosyl)azidoacetamide 35, N-(
N-( -D-glucopyranosyl)propiolamide 39 N-(
-D- glucopyranosyl)-O-propargyl carbamate 43, N-(
8
[
54], 2,3,4,6-tetra-O-acetyl-
60], propargyl 2,3,4,6-tetra-O-acetyl-
-D-galactopyranoside 22 61], 2-bromoethyl 2,3,4,6-tetra-O-acetyl-
-D-galactopyranoside 26 62], 2-
β
-D-glucopyranosyl amine 19
[
β
60], 2,3,4,6-tetra-O-acetyl-
-D-glucopyranoside 21
β
-D-
[
[
61],
β
[
β
[
β
[
β
[
β-
D-galactopyranoside 28
2,3,4,6-tetra-O-acetyl-N-(
[
β
β
[
β
[
glucopyranosyl)-O-propargyl carbamate 41
propargyl carbamate 42
[
β
[
β
β
β
29, 2-azidoethyl
galactopyranosyl)azidoacetamide 36
galactopyranosyl)propiolamide 40 N- (
β
β
β-D-
β-D-
β-D-
,
β
,
β
galactopyranosyl)-O-propargyl carbamate 44 were obtained by Zemplén protocol [67] by deacetylation
of the corresponding sugar derivatives.
3.2. Chemistry
3.2.1. General Procedure for the Synthesis of Quinoline Derivatives 5–10
To a solution of 1,2-dibromoethane or 1,3-dibromopropane or 1,4-dibromobutane (23.1 mmol)
in dry DMF (10 mL), sodium azide (23.1 mmol, 1.5 g) was added. The reaction mixture was stirred
overnight at 50 ◦C. Afterwards, the reaction mixture was diluted with ether and the organic layer was
washed (three times) with H2O (3
sulfate (MgSO4), concentrated under vacuum to afford the corresponding azide as a clear oil, which
was used in the next reaction without further purification.
×
10 mL). The organic layer was dried over anhydrous magnesium
Obtained 1-azido-2-bromoethane or 1-azido-3-bromopropane or 1-azido-4-bromobutane (4.0 mmol),
was added to a solution of 8-hydroxyquinoline
1 or 8-hydroxyquinaldine 2 (4.0 mmol) in acetone
(20 mL), followed by addition of potassium carbonate (10.0 mmol, 1.38 g). The reaction mixture was
heated under reflux for 4 h and then at room temperature overnight. After completion, the reaction
mixture was filtered off and the filtrate was concentrated under vacuum and purified by column
chromatography (toluene:AcOEt; gradient 20:1 to 2:1) to give products 5–10.
8-(2-Azidoethoxy)quinolone
5
: Starting from 1-azido-2-bromoethane and 8-hydroxyquinoline
1
,
24
product was obtained as a brown oil (702.7 mg, 82%); [
CDCl3):
α
]
=
0.6 (c = 1.0, CHCl3); 1H NMR (400 MHz,
−
D
δ
3.87 (t, 2H, J = 5.6 Hz, CH2N), 4.43 (t, 2H, J = 5.6 Hz, CH2O), 7.12 (dd, 1H, J = 2.5 Hz, J =
6.5 Hz, H-7chin), 7.41–7.50 (m, 3H, H-3chin, H-5chin, H-6chin), 8.14 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin),
8.96 (dd, 1H, J = 1.7 Hz, J = 4.2 Hz, H-2chin); 13C NMR (100 MHz, CDCl3):
δ 50.06, 67.64, 109.77, 120.66,
121.70, 126.52, 129.61, 135.95, 140.39, 149.51, 154.19.
8-(3-Azidopropoxy)quinolone
6
: Starting from 1-azido-3-bromopropane and 8-hydroxyquinoline
1
,
24
product was obtained as a brown oil (684.7 mg, 75%); [
CDCl3):
α
]
=
0.4 (c = 1.0, CHCl3); 1H NMR (400 MHz,
−
D
δ
2.28 (p, 2H, J = 6.4 Hz, CH2), 3.65 (t, 2H, J = 6.6 Hz, CH2N), 4.33 (t, 2H, J = 6.2 Hz, CH2O),
7.09 (dd, 1H, J = 1.4 Hz, J = 7.5 Hz, H-7chin), 7.38–7.49 (m, 3H, H-3chin, H-5chin, H-6chin), 8.13 (dd,
1H, J = 1.8 Hz, J = 8.3 Hz, H-4chin), 8.95 (dd, 1H, J = 1.8 Hz, J = 4.2 Hz, H-2chin); 13C NMR (100 MHz,
CDCl3): δ 28.67, 48.44, 65.70, 109.08, 119.97, 121.62, 126.69, 129.55, 136.04, 140.28, 149.31, 154,50.
8-(4-Azidobutoxy)quinoline
7
: Starting from 1-azido-4-bromobutane and 8-hydroxyquinoline
1
,
23
product was obtained as a brown oil (736.5 mg, 76%); [
CDCl3):
4.29 (t, 2H, J = 6.5 Hz, CH2O), 7.07 (dd, 1H, J = 1.2 Hz, J = 7.6 Hz, H-7chin), 7.37–7.49 (m, 3H, H-3chin
H-5chin, H-6chin), 8.14 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.95 (dd, 1H, J = 1.7 Hz, J = 4.2 Hz,
α
]
=
−
0.4 (c = 1.0, CHCl3); 1H NMR (400 MHz,
D
δ
1.90 (p, 2H, J = 7.0 Hz, CH2), 2.11 (p, 2H, J = 6.5 Hz, CH2), 3.42 (t, 2H, J = 6.9 Hz, CH2N),
,

Molecules 2019, 24, 4181
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H-2chin); 13C NMR (100 MHz, CDCl3):
136.06, 140.26, 149.28, 154,59.
δ
25.86, 26.31, 51.29, 68.26, 108.90, 119.72, 121.58, 126.71, 129.56,
2-Methyl-8-(2-azidoethoxy)quinolone
8
: Starting from 1-azido-2-bromoethane and 2-methylo-8-
23
hydroxyquinoline
2
, product was obtained as a brown oil (757.8 mg, 83%); [
α
]
= 0.4 (c = 1.0,
−
D
CHCl3); 1H NMR (400 MHz, CDCl3):
δ
2.79 (s, 3H, CH3), 3.83 (t, 2H, J = 5.5 Hz, CH2N), 4.43 (t, 2H, J =
5.5 Hz, CH2O), 7.10 (dd, 1H, J = 2.6 Hz, J = 6.4 Hz, H-7chin), 7.31 (d, 1H, J = 8.4 Hz, H-3chin), 7.35–7.44
(m, 2H, H-5chin, H-6chin), 8.03 (d, 1H, J = 8.4 Hz, H-4chin); 13C NMR (100 MHz, CDCl3):
δ 25.66, 50.19,
68.05, 110.41, 120.62, 122.57, 125.49, 127.82, 136.00, 140.06, 153.78, 158,36.
2-Methyl-8-(3-azidopropoxy)quinolone
hydroxyquinoline , product was obtained as a brown oil (688.1 mg, 71%); [
CHCl3); 1H NMR (400 MHz, CDCl3):
2.28 (p, 2H, J = 6.5 Hz, CH2), 2.78 (s, 3H, CH3), 3.65 (t, 2H, J =
9: Starting from 1-azido-3-bromopropane and 2-methylo-8-
24
2
α
]
= −0.6 (c = 1.0,
D
δ
6.6 Hz, CH2N), 4.33 (t, 2H, J = 6.3 Hz, CH2O), 7.07 (dd, 1H, J = 2.4 Hz, J = 6.5 Hz, H-7chin), 7.30 (d,
1H, J = 8.4 Hz, H-3chin), 7.33–7.42 (m, 2H, H-5chin, H-6chin), 8.01 (d, 1H, J = 8.4 Hz, H-4chin); 13C NMR
(100 MHz, CDCl3):
154.01, 158,18.
δ 25.71, 28.64, 48.48, 66.03, 109.73, 119.95, 122.52, 125.65, 127.76, 136.11, 140.00,
2-Methyl-8-(4-azidobutoxy)quinoline 10: Starting from 1-azido-4-bromobutane and 2-methylo-8-
22
hydroxyquinoline
2
, product was obtained as a brown oil (707.4 mg, 69%); [
α
]
= 0.6 (c = 1.0,
−
D
CHCl3); 1H NMR (400 MHz, CDCl3):
δ
1.89 (p, 2H, J = 7.0 Hz, CH2), 2.10 (p, 2H, J = 6.7 Hz, CH2), 2.78
(s, 3H, CH3), 3.45 (t, 2H, J = 6.9 Hz, CH2N), 4.27 (t, 2H, J = 6.5 Hz, CH2O), 7.03 (dd, 1H, J = 1.8 Hz, J =
7.1 Hz, H-7chin), 7.29 (d, 1H, J = 8.4 Hz, H-3chin), 7.32–7.41 (m, 2H, H-5chin, H-6chin), 8.00 (d, 1H, J =
8.4 Hz, H-4chin); 13C NMR (100 MHz, CDCl3): δ 25.71, 25.89, 26.24, 51.36, 68.46, 109.35, 119.66, 122.49,
125.64, 127.74, 136.08, 139.91, 154.13, 158,13.
3.2.2. General Procedure for the Synthesis of Sugar Derivatives 31 and 32
To a solution of 2,3,4,6-tetra-O-acetyl-
-D-galactopyranosyl amine 20 (1.7 g, 4.9 mmol) in dry CH2CL2 (20 mL), triethylamine (2 mL) was
added. The reaction mixture was cooled to 0 ◦C and chloroacetyl chloride was added dropwise (613
L,
7.7 mmol) then stirring was continued at room temperature. After 1 h, the resulting mixture was diluted
with dichloromethane (90 mL) and washed with brine (2 60 mL). The combined organic layer was
β-D-glucopyranosyl amine 19 or 2,3,4,6-tetra-O-acetyl-
β
µ
×
dried over anhydrous MgSO4, concentrated under vacuum and purified by column chromatography
(toluene:AcOEt; gradient 8:1 to 2:1) to give products 31–32.
2,3,4,6-Tetra-O-acetyl-N-(
β
β-D-glucopyranosyl)chloroacetamide 31: Starting from 2,3,4,6-tetra-O-acetyl-
-D-glucopyranosyl amine 19, product was obtained as a white solid (1.41 g, 68%); m.p.: 160–163 ◦C;
24
[
α
]
= 8.3 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
δ 2.03, 2.04, 2.06, 2.09 (4s, 12H, CH3CO),
D
3.84 (ddd, 1H, J = 2.1 Hz, J = 4.4 Hz, J = 10.1 Hz, H-5glu), 4.00 and 4.07 (qAB, 2H, J = 15.4 Hz, CH2Cl),
4.10 (dd, 1H, J = 2.1 Hz, J = 12.5 Hz, H-6aglu), 4.31 (dd, 1H, J = 4.4 Hz, J = 12.5 Hz, H-6bglu), 5.01 (dd-t,
1H, J = 9.4 Hz, J = 10.0 Hz, H-1glu), 5.09 (dd-t, 1H, J = 9.4 Hz, J = 10.1 Hz, H-4glu), 5.21 (dd-t, 1H, J =
9.0 Hz, J = 9.4 Hz, H-3glu), 5.33 (dd-t, 1H, J = 9.0 Hz, J = 9.4 Hz, H-2glu), 7.29 (d, 1H, J = 9.0 Hz, CONH);
13C NMR (100 MHz, CDCl3):
δ 20.57, 20.61, 20.72, 20.76, 42.25, 61.56, 68.09, 70.26, 72.55, 73.83, 78.54,
166.81, 169.49, 169.87, 170.58, 170.79; HRMS (ESI-TOF): calcd for C16H22ClNO10Na ([M + Na]+): m/z
446.0830; found: m/z 446.0834.
2,3,4,6-Tetra-O-acetyl-N-(β-D-galactopyranosyl)chloroacetamide 32: Starting from 2,3,4,6-tetra-O-
acetyl-β-◦D-galactopyranosyl amine 20, product was obtained as a white solid (1.66 g, 80%); m.p.:
= 21.3 (c = 1.0, CHCl3); H NMR (400 MHz, CDCl3): δ 2.01, 2.04, 2.07, 2.16 (4s,
D
25
1
143-144 C; [
α
]
12H, CH3CO), 4.01 and 4.08 (qAB, 2H, J = 15.5 Hz, CH2Cl), 4.04-4.18 (m, 3H, H-5gal, H-6agal, H-6bgal),
5.11-5.24 (m, 3H, H-1gal, H-2gal, H-3gal), 5.45 (dd, 1H, J = 0. 7 Hz, J = 3.0 Hz, H-4gal), 7.32 (d, 1H, J =
6.9 Hz, CONH); 13C NMR (100 MHz, CDCl3):
δ 20.54, 20.61, 20.67, 20.71, 42.26, 61.12, 67.10, 67.97,

Molecules 2019, 24, 4181
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70.72, 72.58, 78.84, 166.71, 169.76, 170.01, 170.34, 171.06; HRMS (ESI-TOF): calcd for C16H22ClNO10Na
([M + Na]+): m/z 446.0830; found: m/z 446.0832.
3.2.3. General Procedure for the Synthesis of Sugar Derivatives 33 and 34
To a solution of 2,3,4,6-tetra-O-acetyl-N-(
β-D-glucopyranosyl)chloroacetamide 31 or 2,3,4,6-tetra-O-
acetyl-N-( -D-galactopyranosyl)chloroacetamide 32 (1.0 g, 2.36 mmol) in dry DMF (15 mL), sodium
β
azide (753 mg, 11.59 mmol) was added. The reaction mixture was stirred at room temperature for
24 h. After completion reaction, the solvent was evaporated under reduced pressure, and the residue
was diluted with ethyl acetate (50 mL) and extracted with water (30 mL), 0.25 M HCl (20 mL) and
brine (20 mL). The combined organic layer was dried over anhydrous MgSO4, concentrated under
vacuum, to afford the corresponding azide 33 and 34, which were used for the next reaction without
further purification.
2,3,4,6-tetra-O-acetyl-N-(
N-( -D-glucopyranosyl)chloroacetamide 31, product was obtained as a white solid (975.0 mg, 96%);
m.p.: 150-153 ◦C; [ = 12.4 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
δ 2.03, 2.04, 2.06, 2.09 (4s,
D
β-D-glucopyranosyl)azidoacetamide 33: Starting from 2,3,4,6-tetra-O-acetyl-
β
24
α
]
12H, CH3CO), 3.83 (ddd, 1H, J = 2.1 Hz, J = 4.4 Hz, J = 10.1 Hz, H-5glu), 3.95 and 4.00 (qAB, 2H, J =
16.9 Hz, CH2N), 4.09 (dd, 1H, J = 2.1 Hz, J = 12.5 Hz, H-6aglu), 4.30 (dd, 1H, J = 4.4 Hz, J = 12.5 Hz,
H-6bglu), 4.98 (dd-t, 1H, J = 9.4 Hz, J = 9.8 Hz, H-1glu), 5.08 (dd-t, 1H, J = 9.4 Hz, J = 10.1 Hz, H-4glu),
5.22 (dd-t, 1H, J = 9.0 Hz, J = 9.4 Hz, H-3glu), 5.32 (dd-t, 1H, J = 9.0 Hz, J = 9.8 Hz, H-2glu), 7.10 (d, 1H, J
= 9.1 Hz, CONH); 13C NMR (100 MHz, CDCl3):
δ 20.57, 20.61, 20.72, 20.75, 52.59, 61.56, 68.08, 70.45,
72.57, 73.78, 78.15, 167.41, 169.50, 169.86, 170.57, 170.88; HRMS (ESI-TOF): calcd for C16H22N4O10Na
([M + Na]+): m/z 453.1234; found: m/z 453.1236.
2,3,4,6-tetra-O-acetyl-N-(
N-( -D-galactopyranosyl)chloroacetamide 32, product was obtained as a white solid (873.5 mg, 86%);
m.p.: 60–63 ◦C; [ D = 25.4 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
] δ 2.01, 2.04, 2.07, 2.16 (4s,
β-D-galactopyranosyl)azidoacetamide 34: Starting from 2,3,4,6-tetra-O-acetyl-
β
24
α
12H, CH3CO), 3.96 and 4.01 (qAB, 2H, J = 16.8 Hz, CH2N), 4.02–4.17 (m, 3H, H-5gal, H-6agal, H-6bgal),
5.11–5.25 (m, 3H, H-1gal, H-2gal, H-3gal), 5.45 (dd, 1H, J = 1.1 Hz, J = 2.9 Hz, H-4gal), 7.13 (d, 1H, J =
8.5 Hz, CONH); 13C NMR (100 MHz, CDCl3):
δ 20.54, 20.60, 20.67, 20.70, 52.61, 61.14, 67.11, 68.17,
70.73, 72.52, 78.43, 167.31, 169.76, 170.00, 170.35, 171.15; HRMS (ESI-TOF): calcd for C16H22N4O10Na
([M + Na]+): m/z 453.1234; found: m/z 453.1227.
3.2.4. Synthesis of Glycoconjugates 45–108
The appropriate derivatives of 8-hydoxyquinoline 3–10 (0.5 mmol) and sugar derivatives 21
30 33 44 (0.5 mmol) were dissolved in dry THF (5 mL) and i-PrOH (5 mL). To the obtained
solution, CuSO4 5H2O (0.1 mmol, 25.0 mg) dissolved in H2O (2.5 mL) and sodium ascorbate (0.2 mmol,
–24,
27
–
,
–
·
39.6 mg) dissolved in H2O (2.5 mL) were added. The reaction mixture was stirred for 24 h at room
temperature. The progress of the reaction was monitored on TLC in an CHCl3:CH3OH eluents system
(20:1 for protected or 2:1 for unprotected compounds). After completion, the reaction mixture was
concentrated in vacuo and purified using column chromatography (dry loading; toluene:AcOEt, 2:1
and CHCl3:MeOH, 100:1 for fully protected glycoconjugates or CHCl3:MeOH, gradient: 50:1 to 2:1 for
glycoconjugates with unprotected sugar part) to give products 45–108.
Glycoconjugate 45: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
β
-D-glucopyranoside 21 and
, product was obtained as a yellow solid (219.2 mg, 73%); m.p.: 130–133 ◦C;
36.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
= δ 1.84, 1.97, 2.01, 2.07 (4s, 12H, CH3CO),
8-(2-azidoethoxy)quinoline
5
24
[
α
]
−
D
3.66 (ddd, 1H, J = 2.3 Hz, J = 4.6 Hz, J = 9.8 Hz, H-5glu), 4.10 (dd, 1H, J = 2.3 Hz, J = 12.3 Hz, H-6aglu),
4.21 (dd, 1H, J = 4.6 Hz, J = 12.3 Hz, H-6bglu), 4.63 (d, 1H, J = 8.0 Hz, H-1glu), 4.59–4.70 (m, 2H, CH2N),
4.80 and 4.88 (qAB, 2H, J = 12.7 Hz, CH2C), 4.95 (dd, 1H, J = 8.0 Hz, J = 9.4 Hz H-2glu), 5.01 (t, 2H, J
= 5.2 Hz, CH2O), 5.04 (dd-t, 1H, J = 9.4 Hz, J = 9.8 Hz, H-4glu), 5.13 (dd-t, 1H, J = 9.4 Hz, J = 9.4 Hz,
H-3glu), 7.05 (dd, 1H, J = 2.1 Hz, J = 6.4 Hz, H-7chin), 7.42–7.55 (m, 3H, H-3chin, H-5chin, H-6chin), 8.21

Molecules 2019, 24, 4181
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(d, 1H, J = 8.1 Hz, H-4chin), 8.27 (s, 1H, H-5triaz), 8.99 (d, 1H, J = 2.9 Hz, H-2chin); 13C NMR (100 MHz,
CDCl3): 20.47, 20.48, 20.59, 20.75, 49.75, 61.84, 62.40, 67.89, 68.34, 71.17, 71.82, 72.86, 99.32, 110.31,
δ
121.07, 121.95, 125.10, 126.87, 129.65, 136.68, 139.55, 143.93, 149.26, 153.45, 169.36, 169.40, 170.18, 170.66;
HRMS (ESI-TOF): calcd for C28H33N4O11 ([M + H]+): m/z 601.2146; found: m/z 601.2148.
Glycoconjugate 46: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
β
-D-galactopyranoside 22 and
, product was obtained as a yellow solid (222.2 mg, 74%); m.p.: 69–72 ◦C;
30.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
= δ 1.85, 1.95, 2.05, 2.13 (4s, 12H, CH3CO),
8-(2-azidoethoxy)quinoline
5
24
[
α
]
−
D
3.83-3.92 (m, 1H, H-5gal), 4.10-4.16 (m, 2H, H-6agal, H-6bgal), 4.60 (d, 1H, J = 8.0 Hz, H-1gal), 4.62–4.69
(m, 2H, CH2N), 4.79 and 4.90 (qAB, 2H, J = 12.6 Hz, CH2C), 4.94 (dd, 1H, J = 3.4 Hz, J = 10.4 Hz
H-3gal), 4.97-5.05 (m, 2H, CH2O), 5.17 (dd, 1H, J = 8.0 Hz, J = 10.4 Hz, H-2gal), 5.35 (dd, 1H, J = 0.7 Hz,
J = 3.4 Hz, H-4gal), 6.99–7.12 (m, 1H, H-7chin), 7.38–7.58 (m, 3H, H-3chin, H-5chin, H-6chin), 8.12–8.34
(m, 2H, H-4chin, H-5triaz), 8.99 (bs, 1H, H-2chin); 13C NMR (100 MHz, DMSO-d6):
δ 20.26, 20.28, 20.35,
20.47, 49.18, 61.17, 61.76, 67.25, 67.43, 68.53, 69.91, 70.19, 98.99, 110.74, 120.57, 121.98, 124.93, 126.84,
129.15, 136.26, 139.30, 143.07, 149.00, 153.50, 169.03, 169.41, 169.85, 169.88; HRMS (ESI-TOF): calcd for
C28H33N4O11 ([M + H]+): m/z 601.2146; found: m/z 601.2145.
Glycoconjugate 47: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
β
-D-glucopyranoside 21 and
, product was obtained as a yellow solid (307.3 mg, 100%); m.p.:
32.4 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.83, 1.91, 1.98, 2.02
2-methyl-8-(2-azidoethoxy)quinoline
8
24
119-123 ◦C; [
α
]
−
D
(4s, 12H, CH3CO), 2.69 (s, 3H, CH3), 3.93 (ddd, 1H, J = 2.4 Hz, J = 4.9 Hz, J = 10.0 Hz, H-5glu), 4.01
(dd, 1H, J = 2.4 Hz, J = 12.3 Hz, H-6aglu), 4.15 (dd, 1H, J = 4.9 Hz, J = 12.3 Hz, H-6bglu), 4.59 (t, 2H, J =
4.9 Hz, CH2N), 4.65 and 4.81 (qAB, 2H, J = 12.3 Hz, CH2C), 4.74 (dd, 1H, J = 8.0 Hz, J = 9.6 Hz H-2glu),
4.87 (d, 1H, J = 8.0 Hz, H-1glu), 4.86–4.95 (m, 3H, CH2O, H-4glu), 5.20 (dd-t, 1H, J = 9.6 Hz, J = 9.6 Hz,
H-3glu), 7.20 (dd, 1H, J = 1.2 Hz, J = 7.7 Hz, H-7chin), 7.39-7.46 (m, 2H, H-3chin, H-6chin), 7.50 (dd, 1H, J
= 1.2 Hz, J = 8.2 Hz, H-5chin), 8.20 (d, 1H, J = 8.4 Hz, H-4chin), 8.59 (s, 1H, H-5triaz); 13C NMR (100 MHz,
DMSO-d6):
δ 20.15, 20.22, 20.34, 20.46, 25.01, 49.18, 61.60, 61.90, 67.58, 68.04, 70.58, 70.80, 72.05, 98.51,
111.21, 120.48, 122.52, 125.45, 125.65, 127.35, 136.04, 139.29, 142.89, 153.20, 157.55, 168.88, 169.20, 169.45,
169.99; HRMS (ESI-TOF): calcd for C29H35N4O11 ([M + H]+): m/z 615.2302; found: m/z 615.2304.
Glycoconjugate 48: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
β
-D-galactopyranoside 22 and
, product was obtained as a yellow solid (218.2 mg, 71%); m.p.:
20.8 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.83, 1.89, 2.01, 2.11 (4s,
2-methyl-8-(2-azidoethoxy)quinoline
8
23
52–56 ◦C; [
α
]
−
D
12H, CH3CO), 2.69 (s, 3H, CH3), 3.99–4.10 (m, 2H, H-5gal, H-6agal), 4.13–4.21 (m, 1H, H-6bgal), 4.59 (t,
2H, J = 5.0 Hz, CH2N), 4.64 and 4.81 (qAB, 2H, J = 12.3 Hz, CH2C), 4.79 (d, 1H, J = 8.0 Hz, H-1gal),
4.86–4.97 (m, 3H, CH2O, H-2gal), 5.11 (dd, 1H, J = 0.9 Hz, J = 10.3 Hz, H-4gal), 5.24 (dd, 1H, J = 3.6 Hz, J
= 10.3 Hz, H-3gal), 7.20 (dd, 1H, J = 1.2 Hz, J = 7.7 Hz, H-7chin), 7.38-7.47 (m, 2H, H-3chin, H-6chin), 7.50
(dd, 1H, J = 1.2 Hz, J = 8.2 Hz, H-5chin), 8.21 (d, 1H, J = 8.4 Hz, H-4chin), 8.60 (s, 1H, H-5triaz); 13C NMR
(100 MHz, DMSO-d6):
δ 20.25, 20.28, 20.35, 20.47, 25.01, 49.19, 61.19, 61.76, 67.26, 67.59, 68.53, 69.89,
70.20, 98.94, 111.22, 120.48, 122.52, 125.40, 125.66, 127.35, 136.04, 139.31, 142.97, 153.21, 157.56, 168.98,
169.40, 169.85, 169.89; HRMS (ESI-TOF): calcd for C29H35N4O11 ([M + H]+): m/z 615.2302; found: m/z
615.2303.
Glycoconjugate 49: Starting from propargyl
β
-D-glucopyranoside 23 and 8-(2-azidoethoxy)quinoline
25
5
, product was obtained as a yellow solid (205.4 mg, 95%); m.p.: 42-45 ◦C; [
α
]
= −17.2 (c = 1.0,
D
MeOH); 1H NMR (400 MHz, DMSO-d6):
δ 2.92-3.09 (m, 2H, H-2glu, H-5glu), 3.10-3.17 (m, 2H, H-3glu,
H-4glu), 3.40–3.50 (m, 1H, H-6aglu), 3.66–3.75 (m, 1H, H-6bglu), 4.08 (bs, 1H, OH), 4.27 (d, 1H, J = 7.8 Hz,
H-1glu), 4.57 (bs, 1H, OH), 4.60–4.66 (m, 3H, CH2N, CH2C), 4.83–4.95 (m, 4H, CH2O, CH2C, OH), 5.02
(bs, 1H, OH), 7.25 (dd, 1H, J = 1.5 Hz, J = 7.5 Hz, H-7chin), 7.47–7.58 (m, 3H, H-3chin, H-5chin, H-6chin),
8.32 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.40 (s, 1H, H-5triaz), 8.89 (dd, 1H, J = 1.7 Hz, J = 4.2 Hz,
H-2chin); 13C NMR (100 MHz, DMSO-d6):
δ 49.12, 61.15, 61.47, 67.36, 70.10, 73.37, 76.70, 76.94, 102.14,

Molecules 2019, 24, 4181
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110.57, 120.51, 121.91, 124.96, 126.71, 129.08, 135.85, 139.69, 143.78, 149.27, 153.68; HRMS (ESI-TOF):
calcd for C20H25N4O7 ([M + H]+): m/z 433.1723; found: m/z 433.1723.
Glycoconjugate 50: Starting from propargyl
5
β
-D-galactopyranoside 24 and 8-(2-azidoethoxy)quinoline
, product was obtained as a yellow solid (144.9 mg, 67%); m.p.: 44–45 ◦C; [
α
]
= −12.9 (c = 1.0,
23
D
MeOH); 1H NMR (400 MHz, DMSO-d6): δ 3.21–3.39 (m, 3H, H-2gal, H-3gal, H-4gal), 3.40–3.48 (m, 1H,
H-5gal), 3.50–3.57 (m, 1H, H-6agal), 3.59–3.66 (m, 1H, H-6bgal), 4.21 (d, 1H, J = 7.4 Hz, H-1gal), 4.61 and
4.83 (qAB, 2H, J = 12.2 Hz, CH2C), 4.63 (t, 2H, J = 5.2 Hz, CH2N), 4.90 (t, 2H, J = 5.2 Hz, CH2O), 7.25
(dd, 1H, J = 1.5 Hz, J = 7.5 Hz, H-7chin), 7.47–7.58 (m, 3H, H-3chin, H-5chin, H-6chin), 8.32 (dd, 1H, J =
1.7 Hz, J = 8.3 Hz, H-4chin), 8.40 (s, 1H, H-5triaz), 8.89 (dd, 1H, J = 1.7 Hz, J = 4.2 Hz, H-2chin); 13C NMR
(100 MHz, DMSO-d6):
δ 49.11, 60.52, 61.31, 67.37, 68.18, 70.44, 73.40, 75.32, 102.69, 110.58, 120.51, 121.92,
124.91, 126.70, 129.07, 135.83, 139.70, 143.85, 149.30, 153.69; HRMS (ESI-TOF): calcd for C20H25N4O7
([M + H]+): m/z 433.1723; found: m/z 433.1725.
Glycoconjugate 51: Starting from propargyl
quinoline
(c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
β
-D-glucopyranoside 23 and 2-methyl-8-(2-azidoethoxy)
24
8
, product was obtained as a yellow solid (196.4 mg, 88%); m.p.: 120–121 ◦C; [
α
]
= 20.0
−
D
δ
2.69 (s, 3H, CH3), 2.92–3.08 (m, 2H, H-2glu, H-5glu),
3.09-3.19 (m, 2H, H-3glu, H-4glu), 3.40–3.49 (m, 1H, H-6aglu), 3.66–3.73 (m, 1H, H-6bglu), 4.09 (bs, 1H,
OH), 4.27 (d, 1H, J = 7.8 Hz, H-1glu), 4.33 (bs, 1H, OH), 4.53 (t, 1H, J = 5.6 Hz, OH), 4.60 (t, 2H, J =
5.2 Hz, CH2N), 4.63 and 4.87 (qAB, 2H, J = 12.1 Hz, CH2C), 4.89 (t, 2H, J = 5.2 Hz, CH2O), 4.99 (d,
1H, J = 4.9 Hz, OH), 7.21 (dd, 1H, J = 1.3 Hz, J = 7.7 Hz, H-7chin), 7.39–7.45 (m, 2H, H-3chin, H-6chin),
7.50 (dd, 1H, J = 1.2 Hz, J = 8.2 Hz, H-5chin), 8.20 (d, 1H, J = 8.4 Hz, H-4chin), 8.54 (s, 1H, H-5triaz); 13
NMR (100 MHz, DMSO-d6): 25.11, 49.11, 61.14, 61.48, 67.56, 70.08, 73.35, 76.70, 76.93, 102.19, 111.16,
C
δ
120.45, 122.54, 125.21, 125.66, 127.35, 136.01, 139.28 143.77, 153.21, 157.61; HRMS (ESI-TOF): calcd for
C21H27N4O7 ([M + H]+): m/z 447.1880; found: m/z 447.1882.
Glycoconjugate 52: Starting from propargyl
quinoline
c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
β
-D-galactopyranoside 24 and 2-methyl-8-(2-azidoethoxy)
24
8
, product was obtained as a yellow solid (174.1 mg, 78%); m.p.: 52–54 ◦C; [
α
]
= −15.0
D
(
δ 2.69 (s, 3H, CH3), 3.21–3.38 (m, 4H, H-2gal, H-3gal,
H-4gal, H-5gal), 3.49–3.57 (m, 1H, H-6agal), 3.60–3.66 (m, 1H, H-6bgal), 4.22 (d, 1H, J = 7.3 Hz, H-1gal),
4.32 (d, 1H, J = 4.5 Hz, OH), 4.58 (t, 1H, J = 5.6 Hz, OH), 4.60 (t, 2H, J = 5.2 Hz, CH2N), 4.60 and 4.87
(qAB, 2H, J = 12.0 Hz, CH2C), 4.66 (d, 1H, J = 5.2 Hz, OH), 4.83 (t, 1H, J = 2.2 Hz, OH), 4.89 (t, 2H,
J = 5.2 Hz, CH2O), 7.21 (dd, 1H, J = 1.3 Hz, J = 7.7 Hz, H-7chin), 7.38–7.46 (m, 2H, H-3chin, H-6chin),
7.50 (dd, 1H, J = 1.2 Hz, J = 8.2 Hz, H-5chin), 8.20 (d, 1H, J = 8.4 Hz, H-4chin), 8.54 (s, 1H, H-5triaz); 13
NMR (100 MHz, DMSO-d6): 25.10, 49.11, 60.45, 61.28, 67.57, 68.13, 70.41, 73.42, 75.28, 102.72, 111.18,
C
δ
120.45, 122.53, 125.19, 125.66, 127.35, 136.01, 139.28, 143.79, 153.21, 157.62; HRMS (ESI-TOF): calcd for
C21H27N4O7 ([M + H]+): m/z 447.1880; found: m/z 447.1879.
Glycoconjugate 53: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
azidopropoxy)quinoline
= 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
β
-D-glucopyranoside 21 and 8-(3-
25
6
, product was obtained as a yellow oil (307.3 mg, 100%); [
α
]
= −21.4 (c
D
δ
1.88, 1.92, 1.98, 2.03 (4s, 12H, CH3CO), 2.43 (p, 2H,
J = 6.5 Hz, CH2), 3.99 (ddd, 1H, J = 2.4 Hz, J = 4.9 Hz, J = 10.0 Hz, H-5glu), 4.10 (dd, 1H, J = 2.4 Hz,
J = 12.3 Hz, H-6aglu), 4.15–4.24 (m, 3H, CH2N, H-6bglu), 4.66 (t, 2H, J = 6.9 Hz, CH2O), 4.65 and 4.80
(qAB, 2H, J = 12.1 Hz, CH2C), 4.76 (dd, 1H, J = 8.0 Hz, J = 9.6 Hz H-2glu), 4.88 (d, 1H, J = 8.0 Hz,
H-1glu), 4.91 (dd-t, 1H, J = 9.6 Hz, J = 9.7 Hz, H-4glu), 5.25 (dd-t, 1H, J = 9.6 Hz, J = 9.6 Hz, H-3glu), 7.19
(dd, 1H, J = 1.9 Hz, J = 7.1 Hz, H-7chin), 7.47–7.53 (m, 2H, H-3chin, H-6chin), 7.56 (dd, 1H, J = 4.0 Hz,
J = 8.2 Hz, H-5chin), 8.24 (s, 1H, H-5triaz), 8.33 (dd, 1H, J = 1.6 Hz, J = 8.2 Hz, H-4chin), 8.89 (bs, 1H,
H-2chin); 13C NMR (100 MHz, DMSO-d6):
δ 20.23, 20.25, 20.35, 20.47, 29.57, 46.66, 61.64, 61.85, 65.39,
68.11, 70.61, 70.83, 72.03, 98.47, 109.82, 119.93, 121.85, 124.50, 126.77, 129.03, 135.78, 139.79, 142.94,
149.01, 154.20, 168.92, 169.22, 169.48, 170.01; HRMS (ESI-TOF): calcd for C29H35N4O11 ([M + H]+): m/z
615.2302; found: m/z 615.2303.

Molecules 2019, 24, 4181
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Glycoconjugate 54: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
β
-D-galactopyranoside 22 and
25
8-(3-azidopropoxy)quinoline
6
, product was obtained as a yellow oil (307.3 mg, 100%); [
α
]
= −16.2
D
(c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
δ
1.89, 1.90, 2.01, 2.11 (4s, 12H, CH3CO), 2.43 (p, 2H,
J = 6.4 Hz, CH2), 4.01–4.11 (m, 2H, H-5gal, H-6agal), 4.15–4.24 (m, 3H, H-6bgal, CH2N), 4.64 and 4.79
(qAB, 2H, J = 12.4 Hz, CH2C), 4.66 (t, 2H, J = 6.8 Hz, CH2O), 4.79 (d, 1H, J = 8.0 Hz, H-1gal), 4.92 (dd,
1H, J = 8.0 Hz, J = 10.3 Hz, H-2gal), 5.15 (dd, 1H, J = 3.6 Hz, J = 10.3 Hz, H-3gal), 5.25 (dd, 1H, J = 0.9 Hz,
J = 3.6 Hz, H-4gal), 7.20 (dd, 1H, J = 1.5 Hz, J = 7.4 Hz, H-7chin), 7.46–7.61 (m, 3H, H-3chin, H-5chin
H-6chin), 8.24 (s, 1H, H-5triaz), 8.31–8.35 (m, 1H, H-4chin), 8.90 (bs, 1H, H-2chin); 13C NMR (100 MHz,
DMSO-d6): 20.28, 20.29, 20.35, 20.47, 29.58, 46.66, 61.22, 61.72, 65.39, 67.28, 68.57, 69.91, 70.19, 98.89,
,
δ
109.81, 119.94, 124.47, 125.27, 126.76, 128.16, 128.86, 135.77, 143.00, 148.99, 154.22, 169.03, 169.42, 169.86,
169.89; HRMS (ESI-TOF): calcd for C29H35N4O11 ([M + H]+): m/z 615.2302; found: m/z 615.2302.
Glycoconjugate 55: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
2-methyl-8-(3-azidopropoxy)quinoline , product was obtained as a yellow oil (204.3 mg, 65%);
20.2 (c = 1.0, CHCl3); H NMR (400 MHz, DMSO-d6): 1.88, 1.92, 1.98, 2.03 (4s, 12H,
β-D-glucopyranoside 21 and
9
23
1
[
α
]
=
−
δ
D
CH3CO), 2.42 (p, 2H, J = 6.5 Hz, CH2), 2.67 (s, 3H, CH3), 3.98 (ddd, 1H, J = 2.4 Hz, J = 4.9 Hz, J =
10.0 Hz, H-5glu), 4.04 (dd, 1H, J = 2.4 Hz, J = 12.4 Hz, H-6aglu), 4.15–4.24 (m, 3H, CH2N, H-6bglu),
4.64 and 4.80 (qAB, 2H, J = 12.3 Hz, CH2C), 4.65 (t, 2H, J = 6.9 Hz, CH2O), 4.75 (dd, 1H, J = 8.0 Hz, J
= 9.6 Hz H-2glu), 4.87 (d, 1H, J = 8.0 Hz, H-1glu), 4.91 (dd-t, 1H, J = 9.6 Hz, J = 9.8 Hz, H-4glu), 5.24
(dd-t, 1H, J = 9.6 Hz, J = 9.6 Hz, H-3glu), 7.16 (dd, 1H, J = 1.2 Hz, J = 7.6 Hz, H-7chin), 7.38–7.50 (m, 3H,
H-3chin, H-5chin, H-6chin), 8.19 (d, 1H, J = 8.4 Hz, H-4chin), 8.25 (s, 1H, H-5triaz); 13C NMR (100 MHz,
DMSO-d6):
δ 20.23, 20.24, 20.35, 20.48, 25.05, 29.52, 46.64, 61.64, 61.83, 65.57, 68.11, 70.60, 70.83, 72.03,
98.46, 110.37, 119.86, 122.44, 124.47, 125.70, 127.32, 135.98, 139.32, 142.93, 153.67, 157.30, 168.92, 169.23,
169.48, 170.01; HRMS (ESI-TOF): calcd for C30H37N4O11 ([M + H]+): m/z 629.2459; found: m/z 629.2458.
Glycoconjugate 56: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
2-methyl-8-(3-azidopropoxy)quinoline
8.8 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
(p, 2H, J = 6.3 Hz, CH2), 2.67 (s, 3H, CH3), 4.01–4.11 (m, 2H, H-5gal, H-6agal), 4.15–4.24 (m, 3H, H-6agal
β
-D-galactopyranoside 22 and
24
9
, product was obtained as a yellow oil (242.0 mg, 77%); [
α
]
D
=
−
δ 1.89, 1.90, 2.01, 2.11 (4s, 12H, CH3CO), 2.42
,
CH2N), 4.64 and 4.79 (qAB, 2H, J = 12.6 Hz, CH2C), 4.66 (t, 2H, J = 6.9 Hz, CH2O), 4.78 (d, 1H, J =
8.0 Hz, H-1gal), 4.92 (dd, 1H, J = 8.0 Hz, J = 10.4 Hz, H-2gal), 5.14 (dd, 1H, J = 3.6 Hz, J = 10.4 Hz, H-3gal),
5.25 (dd, 1H, J = 0.9 Hz, J = 3.6 Hz, H-4gal), 7.16 (dd, 1H, J = 0.8 Hz, J = 7.5 Hz, H-7chin), 7.37–7.51 (m,
3H, H-3chin, H-5chin, H-6chin), 8.19 (d, 1H, J = 8.4 Hz, H-4chin), 8.25 (s, 1H, H-5triaz); 13C NMR (100 MHz,
DMSO-d6): δ18.53, 20.28, 20.29, 20.35, 20.48, 29.53, 46.64, 61.23, 61.70, 65.55, 68.57, 69.91, 70.19, 72.20,
98.88, 110.33, 119.87, 122.45, 124.46, 125.71, 127.31, 135.96, 139.32, 143.02, 153.26, 158.61, 169.03, 169.43,
169.87, 169.90; HRMS (ESI-TOF): calcd for C30H37N4O11 ([M + H]+): m/z 629.2459; found: m/z 629.2455.
Glycoconjugate 57: Starting from propargyl
β
-D-glucopyranoside 23 and 8-(3-azidopropoxy)quinoline
24
6
, product was obtained as a white solid (223.2 mg, 100%); m.p.: 77–79 ◦C; [
α
]
= −19.2 (c = 1.0,
D
MeOH); 1H NMR (400 MHz, DMSO-d6):
δ 2.42 (p, 2H, J = 6.4 Hz, CH2), 2.94-3.09 (m, 2H, H-2glu, H-5glu),
3.10-3.17 (m, 2H, H-3glu, H-4glu), 3.40–3.50 (m, 1H, H-6aglu), 3.67–3.75 (m, 1H, H-6bglu), 4.05–4.11 (m,
1H, OH), 4.21 (t, 2H, J = 6.1 Hz, CH2N), 4.27 (d, 1H, J = 7.8 Hz, H-1glu), 4.34 (t, 1H, J = 5.1 Hz, OH), 4.57
(t, 1H, J = 5.9 Hz, OH), 4.64 (t, 1H, J = 7.1 Hz, CH2O), 4.64 and 4.85 (qAB, 2H, J = 12.2 Hz, CH2C), 5.01
(d, 1H, J = 4.9 Hz, OH), 7.20 (dd, 1H, J = 2.2 Hz, J = 6.8 Hz, H-7chin), 7.47–7.58 (m, 3H, H-3chin, H-5chin
H-6chin), 8.29 (s, 1H, H-5triaz), 8.32 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.90 (dd, 1H, J = 1.6 Hz, J =
4.1 Hz, H-2chin); 13C NMR (100 MHz, DMSO-d6):
29.61, 46.61, 61.16, 61.57, 65.43, 70.11, 73.39, 76.69,
,
δ
76.94, 102.14, 109.84, 119.92, 121.86, 124.42, 126.79, 129.04, 135.81, 139.76, 143.89, 149.07, 154.19; HRMS
(ESI-TOF): calcd for C21H27N4O7 ([M + H]+): m/z 447.1880; found: m/z 447.1880.
Glycoconjugate 58: Starting from propargyl
quinoline , product was obtained as a yellow solid (169.7 mg, 76%); m.p.: 50–54 C; [
11.2 (c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
2.42 (p, 2H, J = 6.5 Hz, CH2), 3.22-3.40 (m,
β-D-galactopyranoside 24 and 8-(3-azidopropoxy)
◦
24
6
α
]
=
D
−
δ

Molecules 2019, 24, 4181
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4H, H-2gal, H-3gal, H-4gal, H-5gal), 3.50-3.58 (m, 1H, H-6agal), 3.60–3.66 (m, 1H, H-6bgal), 4.20 (t, 2H, J =
6.0 Hz, CH2N), 4.21 (d, 1H, J = 6.3 Hz, H-1gal), 4.34 (d, 1H, J = 4.4 Hz, OH), 4.57–4.71 (m, 2H, OH), 4.62
and 4.83 (qAB, 2H, J = 12.4 Hz, CH2C), 4.64 (t, 2H, J = 7.0 Hz, CH2O), 4.86 (d, 1H, J = 5.7 Hz, OH),
7.20 (dd, 1H, J = 2.1 Hz, J = 6.8 Hz, H-7chin), 7.46–7.59 (m, 3H, H-3chin, H-5chin, H-6chin), 8.28 (s, 1H,
H-5triaz), 8.32 (dd, 1H, J = 1.6 Hz, J = 8.4 Hz, H-4chin), 8.90 (dd, 1H, J = 1.7 Hz, J = 4.1 Hz, H-2chin); 13
NMR (100 MHz, DMSO-d6): 29.62, 46.61, 60.53, 61.42, 65.44, 68.18, 70.47, 73.39, 75.32, 102.70, 109.85,
C
δ
119.91, 121.85, 124.36, 126.79, 129.04, 135.79, 139.76, 143.96, 149.08, 154.19; HRMS (ESI-TOF): calcd for
C21H27N4O7 ([M + H]+): m/z 447.1880; found: m/z 447.1879.
Glycoconjugate 59: Starting from propargyl
quinoline
1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
β
-D-glucopyranoside 23 and 2-methyl-8-(3-azidopropoxy)
23
9
, product was obtained as a yellow solid (200.3 mg, 87%); m.p.: 47-50 ◦C; [
α
]
= −16.6 (c =
D
δ
2.42 (p, 2H, J = 6.5 Hz, CH2), 2.68 (s, 3H, CH3), 2.93–3.09
(m, 2H, H-2glu, H-5glu), 3.10–3.20 (m, 2H, H-3glu, H-4glu), 3.40–3.50 (m, 1H, H-6aglu), 3.66–3.75 (m, 1H,
H-6bglu), 4.20 (t, 2H, J = 6.2 Hz, CH2N), 4.26 (d, 1H, J = 7.8 Hz, H-1glu), 4.34 (t, 2H, J = 5.0 Hz, OH),
4.56 (t, 1H, J = 5.8 Hz, OH), 4.63 and 4.84 (qAB, 2H, J = 12.2 Hz, CH2C), 4.64 (t, 2H, J = 6.9 Hz, CH2O),
5.00 (d, 1H, J = 4.9 Hz, OH), 7.16 (dd, 1H, J = 1.3 Hz, J = 7.6 Hz, H-7chin), 7.38–7.49 (m, 3H, H-3chin
H-5chin, H-6chin), 8.19 (d, 1H, J = 8.4 Hz, H-4chin), 8.26 (s, 1H, H-5triaz); 13C NMR (100 MHz, DMSO-d6):
25.09, 29.57, 46.60, 61.16, 61.56, 65.57, 70.12, 73.40, 76.70, 76.95, 102.15, 110.35, 119.86, 122.48, 124.40,
,
δ
125.75, 131.21, 136.01, 139.31, 143.15, 150.40, 153.68; HRMS (ESI-TOF): calcd for C22H29N4O7 ([M +
H]+): m/z 461.2036; found: m/z 461.2039.
Glycoconjugate 60: Starting from propargyl
quinoline
(c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
β
-D-galactopyranoside 24 and 2-methyl-8-(3-azidopropoxy)
24
9
, product was obtained as a brown solid (149.7 mg, 65%); m.p.: 50–54 ◦C; [
α
]
= 4.6
−
D
δ
2.42 (p, 2H, J = 6.5 Hz, CH2), 2.67 (s, 3H, CH3),
3.22–3.42 (m, 4H, H-2gal, H-3gal, H-4gal, H-5gal), 3.49–3.57 (m, 1H, H-6agal), 3.60–3.66 (m, 1H, H-6bgal),
4.20 (t, 2H, J = 5.9 Hz, CH2N), 4.21 (d, 1H, J = 7.0 Hz, H-1gal), 4.34 (bs, 1H, OH), 4.54-4.72 (m, 4H,
CH2O, CH2C, OH), 4.77-4.89 (m, 2H, CH2C, OH), 7.16 (dd, 1H, J = 1.2 Hz, J = 7.6 Hz, H-7chin), 7.37-7.50
(m, 3H, H-3chin, H-5chin, H-6chin), 8.19 (d, 1H, J = 8.4 Hz, H-4chin), 8.26 (s, 1H, H-5triaz); 13C NMR
(100 MHz, DMSO-d6):
δ 25.00, 29.56, 46.58, 60.52, 61.40, 65.59, 68.18, 70.48, 73.40, 75.31, 102.71, 110.44,
119.85, 122.51, 124.32, 125.81, 127.34, 136.18, 139.12, 143.96, 153.58, 157.34; HRMS (ESI-TOF): calcd for
C22H29N4O7 ([M + H]+): m/z 461.2036; found: m/z 461.2038.
Glycoconjugate 61: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
β
-D-glucopyranoside 21 and 8-(4-
23
azidobutoxy)quinoline
7
, product was obtained as a yellow oil (301.7 mg, 96%); [
α
]
= −17.8 (c =
D
1.0, CHCl3); 1H NMR (400 MHz, CDCl3): δ 1.61 (bs, 2H, CH2), 1.92, 1.98, 2.01, 2.08 (4s, 12H, CH3CO),
2.26 (p, 2H, J = 7.1 Hz, CH2), 3.69 (ddd, 1H, J = 2.4 Hz, J = 4.7 Hz, J = 9.9 Hz, H-5glu), 4.12 (dd, 1H, J
= 2.4 Hz, J = 12.3 Hz, H-6aglu), 4.24 (dd, 1H, J = 4.7 Hz, J = 12.3 Hz, H-6aglu), 4.28 (t, 2H, J = 6.1 Hz,
CH2N), 4.58 (t, 2H, J = 6.9 Hz, CH2O), 4.68 (d, 1H, J = 8.0 Hz, H-1glu), 4.81 and 4.93 (qAB, 2H, J =
12.6 Hz, CH2C), 5.00 (dd, 1H, J = 8.0 Hz, J = 9.5 Hz H-2glu), 5.08 (dd-t, 1H, J = 9.4 Hz, J = 9.8 Hz, H-4glu),
5.17 (dd-t, 1H, J = 9.4 Hz, J = 9.4 Hz, H-3glu), 7.05 (dd, 1H, J = 1.4 Hz, J = 7.5 Hz, H-7chin), 7.38–7.49 (m,
3H, H-3chin, H-5chin, H-6chin), 7.95 (s, 1H, H-5triaz), 8.14 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.93
(dd, 1H, J = 1.7 Hz, J = 4.2 Hz, H-2chin); 13C NMR (100 MHz, CDCl3):
δ 20.60, 20.67, 20.75, 20.79, 25.61,
27.83, 49.93, 61.85, 62.86, 68.36, 71.24, 71.89, 72.86, 77.22, 99.66, 108.81, 119.91, 121.71, 123.74, 126.69,
129.54, 135.96, 140.35, 143.77, 149.32, 154.59, 169.35, 169.42, 170.19, 170.65; HRMS (ESI-TOF): calcd for
C29H35N4O11 ([M + H]+): m/z 629.2459; found: m/z 629.2458.
Glycoconjugate 62: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
8-(4-azidobutoxy)quinoline
= 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
β
-D-galactopyranoside 22 and
25
7
, product was obtained as a yellow oil (292.3 mg, 93%); [
α
]
= −12.8 (c
D
δ
1.78–1.87 (m, 2H, CH2), 1.90, 1.90, 2.01, 2.10 (4s, 12H,
CH3CO), 2.05–2.10 (m, 2H, CH2), 4.01-4.11 (m, 2H, H-5gal, H-6agal), 4.16-4.25 (m, 3H, H-6bgal, CH2N),
4.54 (t, 2H, J = 7.0 Hz, CH2O), 4.64 and 4.80 (qAB, 2H, J = 12.4 Hz, CH2C), 4.81 (d, 1H, J = 8.0 Hz, H-1gal),
4.92 (dd, 1H, J = 8.0 Hz, J = 10.3 Hz, H-2gal), 5.15 (dd, 1H, J = 3.6 Hz, J = 10.3 Hz, H-3gal), 5.25 (dd, 1H, J

Molecules 2019, 24, 4181
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= 0.9 Hz, J = 3.6 Hz, H-4gal), 7.17–7.21 (m, 1H, H-7chin), 7.47–7.57 (m, 3H, H-3chin, H-5chin, H-6chin), 8.25
(s, 1H, H-5triaz), 8.31 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.85 (bs, 1H, H-2chin); 13C NMR (100 MHz,
DMSO-d6):
δ 20.29, 20.32, 20.35, 20.48, 25.53, 27.04, 49.08, 61.21, 61.81, 67.28, 67.85, 68.58, 69.90, 70.19,
98.97, 109.37, 119.55, 121.79, 124.44, 126.80, 129.00, 135.76, 139.72, 142.87, 148.92, 154.38, 169.05, 169.42,
169.86, 169.89; HRMS (ESI-TOF): calcd for C30H37N4O11 ([M + H]+): m/z 629.2459; found: m/z 629.2459.
Glycoconjugate 63: Starting from propargyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside 21 and
2-methyl-8-(4-azidobutoxy)quinoline 10, product was obtained as a yellow oil (295.6 mg, 92%);
23
[
α
]
= δ 1.80 (p, 2H, J = 6.6 Hz, CH2), 1.88,
18.8 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
−
D
1.91, 1.97, 2.02 (4s, 12H, CH3CO), 2.08 (p, 2H, J = 7.4 Hz, CH2), 2.63 (s, 3H, CH3), 3.97 (ddd, 1H, J =
2.4 Hz, J = 4.9 Hz, J = 10.0 Hz, H-5glu), 4.03 (dd, 1H, J = 2.4 Hz, J = 12.4 Hz, H-6aglu), 4.14–4.24 (m, 3H,
CH2N, H-6bglu), 4.59 (t, 2H, J = 6.9 Hz, CH2O), 4.64 and 4.80 (qAB, 2H, J = 12.4 Hz, CH2C), 4.75 (dd,
1H, J = 8.0 Hz, J = 9.7 Hz H-2glu), 4.90 (d, 1H, J = 8.0 Hz, H-1glu), 4.91 (dd-t, 1H, J = 9.7 Hz, J = 9.7 Hz,
H-4glu), 5.24 (dd-t, 1H, J = 9.6 Hz, J = 9.6 Hz, H-3glu), 7.15 (dd, 1H, J = 1.8 Hz, J = 7.2 Hz, H-7chin),
7.38–7.47 (m, 3H, H-3chin, H-5chin, H-6chin), 8.18 (d, 1H, J = 8.4 Hz, H-4chin), 8.34 (s, 1H, H-5triaz); 13
NMR (100 MHz, DMSO-d6): 20.23, 20.30, 20.34, 20.47, 24.93, 25.25, 27.23, 49.08, 61.64, 61.92, 68.09,
C
δ
68.14, 70.60, 70.82, 72.03, 98.53, 109.64, 119.42, 122.41, 124.62, 125.74, 127.26, 135.96, 139.19, 142.70,
153.89, 157.21, 168.92, 169.21, 169.46, 170.00; HRMS (ESI-TOF): calcd for C31H39N4O11 ([M + H]+): m/z
643.2615; found: m/z 643.2618.
Glycoconjugate 64: Starting from propargyl 2,3,4,6-tetra-O-acetyl-
2-methyl-8-(4-azidobutoxy)quinoline 10, product was obtained as a yellow oil (321.3 mg, 100%); [
β
-D-galactopyranoside 22 and
24
α
]
D
=
−
13.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
δ
1.81 (p, 2H, J = 6.6 Hz, CH2), 1.89, 1.89, 2.00,
2.10 (4s, 12H, CH3CO), 2.03–2.10 (m, 2H, CH2), 2.63 (s, 3H, CH3), 4.01–4.11 (m, 2H, H-5gal, H-6agal),
4.15–4.25 (m, 3H, H-6agal, CH2N), 4.59 (t, 2H, J = 7.0 Hz, CH2O), 4.64 and 4.80 (qAB, 2H, J = 12.9 Hz,
CH2C), 4.81 (d, 1H, J = 8.0 Hz, H-1gal), 4.92 (dd, 1H, J = 8.0 Hz, J = 10.3 Hz, H-2gal), 5.14 (dd, 1H, J =
3.6 Hz, J = 10.3 Hz, H-3gal), 5.24 (dd, 1H, J = 0.9 Hz, J = 3.6 Hz, H-4gal), 7.15 (dd, 1H, J = 1.8 Hz, J =
7.2 Hz, H-7chin), 7.38–7.47 (m, 3H, H-3chin, H-5chin, H-6chin), 8.18 (d, 1H, J = 8.4 Hz, H-4chin), 8.33 (s, 1H,
H-5triaz); 13C NMR (100 MHz, DMSO-d6):
δ 20.22, 20.28, 20.34, 20.47, 24.93, 25.26, 27.25, 49.08, 61.20,
61.78, 67.28, 68.14, 68.57, 69.89, 70.19, 98.95, 109.64, 119.41, 122.40, 124.57, 125.74, 127.26, 135.96, 139.19,
142.78, 153.89, 157.21, 168.02, 169.41, 169.84, 169.88; HRMS (ESI-TOF): calcd for C31H39N4O11 ([M +
H]+): m/z 643.2615; found: m/z 643.2612.
Glycoconjugate 65: Starting from propargyl
β
-D-glucopyranoside 23 and 8-(4-azidobutoxy)quinoline
7
,
product was obtained as a yellow solid (165.8 mg, 72%); m.p.: 49–51 ◦C; [
α
]
= −20.2 (c = 1.0, MeOH);
24
D
1H NMR (400 MHz, DMSO-d6):
δ 1.77-1.89 (m, 2H, CH2), 2.03-2.15 (m, 2H, CH2), 2.94–3.09 (m, 2H,
H-2glu, H-5glu), 3.10–3.17 (m, 2H, H-3glu, H-4glu), 3.40–3.50 (m, 1H, H-6aglu), 3.67–3.75 (m, 1H, H-6bglu),
4.05–4.11 (m, 1H, OH), 4.21 (m, 2H, CH2N), 4.27 (d, 1H, J = 7.8 Hz, H-1glu), 4.34 (t, 1H, J = 5.1 Hz, OH),
4.52 (t, 1H, J = 6.8 Hz, CH2O), 4.57 (t, 1H, J = 5.9 Hz, OH), 4.64 and 4.85 (qAB, 2H, J = 12.2 Hz, CH2C),
5.01 (d, 1H, J = 4.9 Hz, OH), 7.17–7.22 (m, 1H, H-7chin), 7.45–7.61 (m, 3H, H-3chin, H-5chin, H-6chin), 8.28
(s, 1H, H-5triaz), 8.31–8.35 (m, 1H, H-4chin), 8.87 (bs, 1H, H-2chin); 13C NMR (100 MHz, DMSO-d6):
δ
25.61, 26.96, 49.06, 61.16, 61.59, 67.84, 70.11, 73.38, 76.70, 76.95, 102.15, 109.35, 119.64, 121.85, 124.42,
126.84, 128.86, 135.68, 139.79, 143.73, 148.98, 154.35; HRMS (ESI-TOF): calcd for C22H29N4O7 ([M +
H]+): m/z 461.2036; found: m/z 461.2036.
Glycoconjugate 66: Starting from propargyl
β
-D-galactopyranoside 24 and 8-(4-azidobutoxy)quinoline
24
7
, product was obtained as a yellow solid (207.2 mg, 90%); m.p.: 62–64 ◦C; [
α
]
= −13.0 (c = 1.0,
D
MeOH); 1H NMR (400 MHz, DMSO-d6):
δ 1.83 (p, 2H, J = 6.3 Hz, CH2), 2.08 (p, 2H, J = 7.1 Hz, CH2),
3.24–3.30 (m, 1H, H-2gal), 3.33–3.48 (m, 3H, H-3gal, H-4gal, H-5gal), 3.50–3.57 (m, 1H, H-6agal), 3.61–3.66
(m, 1H, H-6bgal), 4.21 (t, 2H, J = 6.3 Hz, CH2N), 4.22 (d, 1H, J = 7.5 Hz, H-1gal), 4.31–4.36 (m, 2H, OH),
4.52 (t, 2H, J = 7.0 Hz, CH2O), 4.62 and 4.83 (qAB, 2H, J = 12.1 Hz, CH2C), 4.67 (d, 1H, J = 5.1 Hz, OH),
4.87 (d, 1H, J = 4.6 Hz, OH), 7.17–7.21 (m, 1H, H-7chin), 7.46–7.57 (m, 3H, H-3chin, H-5chin, H-6chin),

Molecules 2019, 24, 4181
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8.27 (s, 1H, H-5triaz), 8.31 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.87 (dd, 1H, J = 1.7 Hz, J = 4.1 Hz,
H-2chin); 13C NMR (100 MHz, DMSO-d6):
25.59, 26.98, 49.03, 60.52, 61.45, 67.82, 68.18, 70.47, 73.40,
δ
75.32, 102.73, 109.39, 119.55, 121.80, 124.33, 126.80, 129.00, 135.75, 139.71, 143.77, 148.99, 154.38; HRMS
(ESI-TOF): calcd for C22H29N4O7 ([M + H]+): m/z 461.2036; found: m/z 461.2035.
Glycoconjugate 67: Starting from propargyl
β
-D-glucopyranoside 23 and 2-methyl-8-(4-azidobutoxy)
quinoline 10, product was obtained as an orange solid (180.3 mg, 76%); m.p.: 75–78 ◦C; [
α
]
= −17.6
24
D
(c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
δ 1.82 (p, 2H, J = 6.5 Hz, CH2), 2.08 (p, 2H, J = 7.0 Hz,
CH2), 2.64 (s, 3H, CH3), 2.94–3.09 (m, 2H, H-2glu, H-5glu), 3.10–3.19 (m, 2H, H-3glu, H-4glu), 3.41–3.49
(m, 1H, H-6aglu), 3.66–3.74 (m, 1H, H-6bglu), 4.20 (t, 2H, J = 6.3 Hz, CH2N), 4.27 (d, 1H, J = 7.8 Hz,
H-1glu), 4.55 (d, 1H, J = 5.9 Hz, OH), 4.56 (t, 2H, J = 6.9 Hz, CH2O), 4.64 and 4.86 (qAB, 2H, J = 12.2 Hz,
CH2C), 4.89 (t, 2H, J = 5.2 Hz, OH), 4.91 (t, 1H, J = 4.7 Hz, OH), 5.01 (d, 1H, J = 4.9 Hz, OH), 7.15
(dd, 1H, J = 1.8 Hz, J = 7.1 Hz, H-7chin), 7.38–7.47 (m, 3H, H-3chin, H-5chin, H-6chin), 8.18 (d, 1H, J =
8.4 Hz, H-4chin), 8.31 (s, 1H, H-5triaz); 13C NMR (100 MHz, DMSO-d6):
δ 25.40, 25.44, 27.09, 49.07,
61.13, 61.55, 68.07, 70.09, 73.37, 76.69, 76.93, 102.13, 109.62, 119.44, 122.43, 124.51, 125.78, 127.28, 135.98,
139.16, 145.72, 148.08, 153.85; HRMS (ESI-TOF): calcd for C23H31N4O7 ([M + H]+): m/z 475.2193; found:
m/z 475.2194.
Glycoconjugate 68: Starting from propargyl
β
-D-galactopyranoside 24 and 2-methyl-8-(4-azidobutoxy)
quinoline 10, product was obtained as an orange solid (156.6 mg, 66%); m.p.: 38–41 ◦C; [
α
]
= −6.0 (c
23
D
= 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
δ 1.82 (m, 2H, CH2), 2.08 (m, 2H, CH2), 2.64 (s, 3H,
CH3), 3.23–3.43 (m, 4H, H-2gal, H-3gal, H-4gal, H-5gal), 3.49–3.58 (m, 1H, H-6agal), 3.61–3.66 (m, 1H,
H-6bgal), 4.15–4.25 (m 3H, H-1gal, CH2N), 4.56 (t, 2H, J = 6.8 Hz, CH2O), 4.62 and 4.83 (qAB, 2H, J
= 12.1 Hz, CH2C), 7.16 (m, 1H, H-7chin), 7.36–7.52 (m, 3H, H-3chin, H-5chin, H-6chin), 8.19 (d, 1H, J =
8.2 Hz, H-4chin), 8.29 (s, 1H, H-5triaz); 13C NMR (100 MHz, DMSO-d6):
δ 24.94, 25.40, 27.10, 49.06, 60.50,
61.43, 68.08, 68.17, 70.47, 73.41, 75.31, 102.73, 109.74, 119.43, 122.45, 124.40, 125.81, 127.28, 136.09, 139.06,
143.74, 153.83, 157.26; HRMS (ESI-TOF): calcd for C23H31N4O7 ([M + H]+): m/z 475.2193; found: m/z
475.2199.
Glycoconjugate 69: Starting from 2-azidoethyl 2,3,4,6-tetra-O-acetyl-
β
-D-glucopyranoside 27 and
, product was obtained as a yellow solid (234.2 mg, 78%); m.p.:
13.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
= δ 1.92, 1.98, 2.02, 2.06 (4s, 12H,
8-(2-propyn-1-yloxy)quinoline
3
22
52–55 ◦C; [
α
]
−
D
CH3CO), 3.67 (ddd, 1H, J = 2.4 Hz, J = 4.7 Hz, J = 10.0 Hz, H-5glu), 3.93–3.99 (m, 1H, CH2O), 4.11
(dd, 1H, J = 2.4 Hz, J = 12.4 Hz, H-6aglu), 4.19–4.24 (m, 2H, H-6bglu, CH2O.), 4.48 (d, 1H, J = 7.9 Hz,
H-1glu), 4.49–4.62 (m, 2H, CH2N), 4.95 (dd, 1H, J = 7.9 Hz, J = 9.5 Hz H-2glu), 5.04 (dd, 1H, J = 9.4 Hz,
J = 10.0 Hz, H-4glu), 5.16 (dd-t, 1H, J = 9.4 Hz, J = 9.5 Hz, H-3glu), 5.54 (s, 2H, CH2Ochin), 7.32–7.50
(m, 4H, H-3chin, H-5chin, H-6chin, H-7chin), 7.84 (s, 1H, H-5triaz), 8.14 (d, 1H, J = 8.0 Hz, H-4chin), 8.94
(bs, 1H, H-2chin); 13C NMR (100 MHz, CDCl3):
δ 20.53, 20.55, 20.64, 20.70, 50.06, 61.74, 62.79, 67.58,
68.25, 70.90, 71.99, 72.52, 100.54, 110.09, 120.29, 121.63, 124.62, 126.77, 129.50, 136.05, 140.21, 143.85,
149.26, 153.90, 169.29, 169.35, 170.08, 170.54; HRMS (ESI-TOF): calcd for C28H33N4O11 ([M + H]+): m/z
601.2146; found: m/z 601.2149.
Glycoconjugate 70: Starting from 2-azidoethyl 2,3,4,6-tetra-O-acetyl-
β
-D-galactopyranoside 28 and
, product was obtained as a yellow solid (186.2 mg, 62%); m.p.:
18.4 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.90, 2.00, 2.09, 2.10 (4s,
8-(2-propyn-1-yloxy)quinoline
3
23
55–58 ◦C; [
α
]
−
D
12H, CH3CO), 3.91–3.99 (m, 1H, CH2O), 4.00-4.22 (m, 4H, H-6agal, H-6bgal, H-5gal, CH2O), 4.53–4.66
(m, 2H, CH2N), 4.74 (d, 1H, J = 8.0 Hz, H-1gal), 4.91 (dd, 1H, J = 8.0 Hz, J = 10.4, H-2gal), 5.12 (dd, 1H, J
= 3.6 Hz, J = 10.4 Hz, H-3gal), 5.25 (dd, 1H, J = 0.8 Hz, J = 3.6 Hz, H-4gal), 5.35 (s, 2H, CH2Ochin), 7.41
(dd, 1H, J = 3.4 Hz, J = 5.6 Hz, H-7chin), 7.50–7.57 (m, 3H, H-3chin, H-5chin, H-6chin), 8.15 (s, 1H, H-5triaz),
8.31 (dd, 1H, J = 1.6 Hz, J = 8.3 Hz, H-4chin), 8.83 (bs, 1H, H-2chin); 13C NMR (100 MHz, DMSO-d6):
δ
20.28, 20.32, 20.34, 20.47, 49.34, 61.21, 61.88, 67.26, 68.31, 69.98, 70.08, 79.14, 99.61, 110.10, 120.05,

Molecules 2019, 24, 4181
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121.82, 124.97, 126.72, 129.03, 135.75, 139.75, 142.46, 148.92, 153.85, 169.13, 169.43, 169.86, 169.88; HRMS
(ESI-TOF): calcd for C28H33N4O11 ([M + H]+): m/z 601.2146; found: m/z 601.2140.
Glycoconjugate 71: Starting from 2-azidoethyl 2,3,4,6-tetra-O-acetyl-
β
-D-glucopyranoside 27 and
, product was obtained as a pink solid (298.1 mg, 97%); m.p.:
13.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.89, 1.92, 1.98, 2.01 (4s,
2-methyl-8-(2-propyn-1-yloxy)quinoline
4
24
50–53 ◦C; [
α
]
−
D
12H, CH3CO), 2.63 (s, 3H, CH3), 3.91–4.00 (m, 2H, H-5glu, CH2O), 4.04 (dd, 1H, J = 2.5 Hz, J = 12.4 Hz,
H-6aglu), 4.09–4.13 (m, 1H, CH2O), 4.17 (dd, 1H, J = 5.0 Hz, J = 12.4 Hz, H-6bglu), 4.52–4.66 (m, 2H,
CH2N), 4.75 (dd, 1H, J = 8.1 Hz, J = 9.7 Hz, H-2glu), 4.85 (d, 1H, J = 8.1 Hz, H-1glu), 4.90 (dd-t, 1H, J =
9.4 Hz, J = 9.8 Hz, H-4glu), 5.23 (dd-t, 1H, J = 9.4 Hz, J = 9.7 Hz, H-3glu), 5.34 (s, 2H, CH2Ochin), 7.37
(dd, 1H, J = 1.7 Hz, J = 7.4 Hz, H-7chin), 7.41 (d, 1H, J = 8.4 Hz, H-3chin), 7.43 (dd, 1H, J = 7.4 Hz, J
= 8.1 Hz, H-6chin), 7.47 (dd, 1H, J = 1.7 Hz, J = 8.1 Hz, H-5chin), 8.16 (s, 1H, H-5triaz), 8.18 (d, 1H, J =
8.4 Hz, H-4chin); 13C NMR (100 MHz, DMSO-d6):
δ 20.19, 20.20, 20.31, 20.43, 24.85, 49.27, 61.60, 61.71,
67.39, 68.07, 70.51, 71.87, 79.12, 99.12, 110.26, 119.83, 122.40, 125.05, 125.60, 127.29, 135.90, 139.17, 142.50,
153.34, 157.19, 168.98, 169.19, 169.44, 169.97; HRMS (ESI-TOF): calcd for C29H35N4O11 ([M + H]+): m/z
615.2302; found: m/z 615.2303.
Glycoconjugate 72: Starting from 2-azidoethyl 2,3,4,6-tetra-O-acetyl-
β
-D-galactopyranoside 28 and
, product was obtained as a pink solid (236.6 mg, 77%); m.p.:
13.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.89, 1.90, 2.00, 2.10 (4s,
2-methyl-8-(2-propyn-1-yloxy)quinoline
4
24
60–63 ◦C; [
α
]
−
D
12H, CH3CO), 2.62 (s, 3H, CH3), 3.95 (m, 1H, CH2O), 4.00–4.08 (m, 2H, H-6agal, H-6bgal), 4.08–4.21 (m,
2H, CH2O, H-5gal), 4.52–4.66 (m, 2H, CH2N), 4.74 (d, 1H, J = 8.0 Hz, H-1gal), 4.92 (dd, 1H, J = 8.0 Hz, J
= 10.4, H-2gal), 5.12 (dd, 1H, J = 3.6 Hz, J = 10.4 Hz H-3gal), 5.25 (dd, 1H, J = 0.8 Hz, J = 3.6 Hz, H-4gal),
5.34 (s, 2H, CH2Ochin), 7.37 (dd, 1H, J = 1.6 Hz, J = 7.4 Hz, H-7chin), 7.41 (d, 1H, J = 8.4 Hz, H-3chin),
7.43 (dd, 1H, J = 7.4 Hz, J = 8.2 Hz, H-6chin), 7.47 (dd, 1H, J = 1.6 Hz, J = 8.2 Hz, H-5chin), 8.15 (s, 1H,
H-5triaz), 8.18 (d, 1H, J = 8.4 Hz, H-4chin); 13C NMR (100 MHz, DMSO-d6):
δ 20.30, 20.37, 20.50, 21.05,
24.89, 49.36, 61.23, 61.79, 67.29, 68.31, 70.01, 70.11, 79.17, 99.65, 110.33, 119.90, 122.46, 125.05, 125.67,
127.35, 135.96, 139.23, 142.58, 153.40, 157.25, 169.18, 169.46, 169.89, 169.9k2; HRMS (ESI-TOF): calcd for
C29H35N4O11 ([M + H]+): m/z 615.2302; found: m/z 615.2305.
Glycoconjugate 73: Starting from 2-azidoethyl
quinoline , product was obtained as a beige solid (134.1 mg, 62%); m.p.: 60–63 C; [
(c = 1.0, MeOH); H NMR (400 MHz, DMSO-d6):
β-D-glucopyranoside 29 and 8-(2-propyn-1-yloxy)
◦
23
3
α
]
=
−
9.6
D
1
δ
2.95-3.08 (m, 1H, H-5glu), 3.10–3.19 (m, 3H,
H-2glu, H-3glu, H-4glu), 3.40-3.48 (m, 1H, H-6aglu), 3.65–3.72 (m, 1H, H-6bglu), 3.91–3.98 (m, 1H, CH2O),
4.07-4.14 (m, 1H, CH2O), 4.26 (d, 1H, J = 7.8 Hz, H-1glu), 4.52–4.56 (m, 1H, OH), 4.60–4.66 (m, 2H,
CH2N), 4.88–4.96 (m, 2H, OH), 5.10–5.14 (d, 1H, J = 4.7 Hz, OH), 5.34 (s, 2H, CH2Ochin), 7.39–7.45 (m,
1H, H-7chin), 7.50–7.57 (m, 3H, H-3chin, H-5chin, H-6chin), 8.32 (dd, 1H, J = 1.8 Hz, J = 8.1 Hz, H-4chin),
8.38 (s, 1H, H-5triaz), 8.83 (dd, 1H, J = 1.8 Hz, J = 4.1 Hz, H-2chin); 13C NMR (100 MHz, DMSO-d6):
δ
49.74, 61.06, 61.82 67.36, 70.01, 73.27, 76.59, 76.96, 102.95, 109.96, 119.95, 121.81, 125.69, 126.73, 129.03,
135.78, 139.67, 142.32, 148.96, 153.84; HRMS (ESI-TOF): calcd for C20H25N4O7 ([M + H]+): m/z 433.1723;
found: m/z 433.1719.
Glycoconjugate 74: Starting from 2-azidoethyl
quinoline
NMR (400 MHz, D2O):
β
-D-galactopyranoside 30 and 8-(2-propyn-1-yloxy)
25
3
, product was obtained as a brown oil (118.9 mg, 55%); [
α
]
D = 10.8 (c = 1.0, MeOH); 1H
δ
3.44-3.54 (m, 1H, H-2gal), 3.57–3.74 (m, 4H, H-3gal, H-5gal, H-6agal, H-6bgal),
3.91 (d, 1H, J = 3.2 Hz, H-4gal), 4.11-4.21 (m, 1H, CH2O), 4.30–4.40 (m, 2H, CH2O, H-1gal), 4.72-4.78 (m,
2H, CH2Ntriaz), 5.66 (s, 2H, CH2Ochin), 7.78 (dd, 1H, J = 2.3 Hz, J = 6.4 Hz, H-7chin), 7.85-7.97 (m, 2H,
H-3chin, H-5chin), 8.06–8.16 (m, 1H, H-6chin), 8.35 (s, 1H, H-5triaz), 9.05 (d, 1H, J = 4.7 Hz, H-2chin), 9.14
(d, 1H, J = 8.1 Hz, H-4chin); 13C NMR (100 MHz, D2O):
δ 50.49, 60.83, 62.27, 67.96, 68.45, 70.52, 72.54,
75.05, 102.97, 114.63, 120.83, 122.17, 126.24, 129.37, 129.92, 130.37, 142.07, 143.05, 147.30, 147.5; HRMS
(ESI-TOF): calcd for C20H25N4O7 ([M + H]+): m/z 433.1723; found: m/z 433.1720.

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Glycoconjugate 75: Starting from 2-azidoethyl
β
-D-glucopyranoside 29 and 2-methyl-8-(2-propyn-1-
24
yloxy)quinoline
4
, product was obtained as a brown oil (129.5 mg, 58%); [
α
]
= 1.6 (c = 1.0, MeOH);
D
1H NMR (400 MHz, D2O):
δ
3.01 (s, 3H, CH3), 3.18 (dd-t, 1H, J = 8.2 Hz, J = 8.3 Hz, H-4glu), 3.29 (dd-t,
1H, J = 8.6 Hz, J = 9.0 Hz, H-2glu), 3.38–3.47 (m, 2H, H-3glu, H-5glu), 3.63 (dd, 1H, J = 4.7 Hz, J = 12.3 Hz,
H-6aglu), 3.81–3.90 (m, 1H, H-6bglu), 4.10–4.22 (m, 1H, CH2O), 4.27–4.37 (m, 1H, CH2O), 4.41 (d, 1H, J
= 7.8 Hz, H-1glu), 4.68–4.77 (m, 2H, CH2N), 5.64 (s, 2H, CH2Ochin), 7.64–7.96 (m, 4H, H-3chin, H-5chin
,
H-6chin, H-7chin), 8.30 (s, 1H, H-5triaz), 8.91 (d, 1H, J = 8.3 Hz, H-4chin); 13C NMR (100 MHz, D2O):
δ
19.99, 50.45, 60.60, 62.10, 67.96, 69.49, 72.88, 75.53, 75.82, 102.32, 114.65, 120.85, 124.20, 126.25, 128.08,
129.08, 129.44, 146.30, 146.98, 155.63, 157.49; HRMS (ESI-TOF): calcd for C21H27N4O7 ([M + H]+): m/z
447.1880; found: m/z 447.1880.
Glycoconjugate 76: Starting from 2-azidoethyl
yloxy)quinoline
(c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
β
-D-galactopyranoside 30 and 2-methyl-8-(2-propyn-1-
23
4
, product was obtained as a pink solid (131.7 mg, 59%); m.p.: 102-105 ◦C; [
α
]
= 4.8
D
δ
2.63 (s, 3H, CH3), 3.33–3.39 (m, 2H, H-2gal, H-3gal),
3.40–3.48 (m, 1H, H-5gal), 3.49–3.55 (m, 2H, H-6agal, H-6bgal), 3.63 (dd-t, 1H, J = 0.8 Hz, J = 3.6 Hz,
H-4gal), 3.88–3.96 (m, 1H, CH2O), 4.06–4.14 (m, 1H, CH2O), 4.19 (d, 1H, J = 7.3 Hz, H-1gal), 4.35 (d, 1H,
J = 4.6 Hz, OH), 4.53–4.64 (m, 3H, CH2N, OH), 4.69 (d, 1H, J = 5.0 Hz, OH), 4.95 (d, 1H, J = 4.4 Hz, OH),
5.33 (s, 2H, CH2Ochin), 7.38 (dd, 1H, J = 2.0 Hz, J = 7.2 Hz, H-7chin), 7.41 (d, 1H, J = 8.4 Hz, H-3chin),
7.44 (dd, 1H, J = 7.2 Hz, J = 7.8 Hz, H-6chin), 7.47 (dd, 1H, J = 1.8 Hz, J = 7.8 Hz, H-5chin), 8.18 (d, 1H, J =
8.4 Hz, H-4chin), 8.37 (s, 1H, H-5triaz); 13C NMR (100 MHz, DMSO-d6):
δ 24.89, 49.75, 60.46, 61.66, 67.16,
68.14, 70.35, 73.29, 75.39, 103.53, 110.20, 119.77, 122.42, 125.65, 125.69, 127.30, 135.93, 139.16, 142.39,
153.37, 157.23; HRMS (ESI-TOF): calcd for C21H27N4O7 ([M + H]+): m/z 447.1880; found: m/z 447.1881.
Glycoconjugate 77: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-glucopyranosyl)azidoacetamide 33 and
, product was obtained as a light yellow solid (205.5 mg, 67%); m.p.:
1.94, 1.97, 1.99, 2.00 (4s, 12H,
8-(2-propyn-1-yloxy)quinoline
3
25
97–100 ◦C; [
α
]
D = 4.4 (c = 0.6, CHCl3); 1H NMR (400 MHz, DMSO-d6):
δ
CH3CO), 3.99 (m, 1H, H-6aglu), 4.10–4.18 (m, 2H, H-5glu, H-6bglu), 4.87 (dd-t, 1H, J = 9.4 Hz, J = 9.4 Hz,
H-4glu), 4.93 (dd-t, 1H, J = 9.7 Hz, J = 9.7 Hz, H-2glu), 5.16 and 5.22 (qAB, 2H, J = 16.5 Hz, CH2CO),
5.34–5.41 (m, 3H, H-1glu, CH2Ochin), 5.45 (dd-t, 1H, J = 9.4 Hz, J = 9.4 Hz, H-3glu), 7.41 (dd, 1H, J =
3.6 Hz, J = 5.4 Hz, H-7chin), 7.49–7.57 (m, 3H, H-3chin, H-5chin, H-6chin), 8.24 (s, 1H, H-5triaz), 8.32 (dd,
1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.83 (d, 1H, J = 2.7 Hz, H-2chin), 9.25 (d, 1H, J = 9.3 Hz, CONH); 13
NMR (100 MHz, DMSO-d6): 20.27, 20.30, 20.33, 20.48, 51.40, 61.73, 67.72, 70.58, 72.13, 72.64, 76.85,
C
δ
79.12, 109.94, 119.95, 121.81, 126.38, 126.69, 129.02, 135.73, 139.70, 142.37, 148.94, 153.82, 166.17, 169.13,
169.25, 169.44, 169.94; HRMS (ESI-TOF): calcd for C28H32N5O11 ([M + H]+): m/z 614.2098; found: m/z
614.2095.
Glycoconjugate 78: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-galactopyranosyl)azidoacetamide 34
, product was obtained as a yellow solid (227.0 mg, 74%); m.p.:
1.92, 1.98, 1.99, 2.12 (4s,
and 8-(2-propyn-1-yloxy)quinoline
3
22
100–103 ◦C; [
α
]
D = 14.8 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
δ
12H, CH3CO), 3.98 (dd, 1H, J = 6.7 Hz, J = 11.3 Hz, H-6agal), 4.05 (dd, 1H, J = 5.9 Hz, J = 11.3 Hz,
H-6bgal), 4.35 (m, 1H, H-5gal), 5.08 (dd, 1H, J = 9.0 Hz, J = 9.4 Hz, H-2gal), 5.13 and 5.21 (qAB, 2H, J
= 16.5 Hz, CH2CO), 5.27-5.44 (m, 5H, H-1gal, H-3gal, H-4gal, CH2Ochin), 7.42 (dd, 1H, J = 3.2 Hz, J =
5.8 Hz, H-7chin), 7.50–7.58 (m, 3H, H-3chin, H-5chin, H-6chin), 8.24 (s, 1H, H-5triaz), 8.28–8.35 (m, 2H,
H-4chin, H-2chin), 9.34 (d, 1H, J = 9.5 Hz, CONH); 13C NMR (100 MHz, DMSO-d6):
δ 20.33, 20.38, 20.48,
20.72, 51.37, 61.42, 61.75, 67.54, 68.24, 70.66, 71.43, 77.22, 109.95, 119.98, 121.88, 124.11, 126.39, 126.70,
135.73, 139.72, 142.38, 148.91, 153.85, 166.09, 169.31, 169.37, 169.78, 169.85; HRMS (ESI-TOF): calcd for
C28H32N5O11 ([M + H]+): m/z 614.2098; found: m/z 614.2091.
Glycoconjugate 79: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-glucopyranosyl)azidoacetamide 33 and
, product was obtained as a pink solid (254.2 mg, 81%); m.p.:
= 5.2 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
δ 1.94, 1.97, 1.99, 2.00 (4s, 12H,
D
2-methyl-8-(2-propyn-1-yloxy)quinoline
4
27
93–96 ◦C; [
α
]
CH3CO), 2.63 (s, 3H, CH3), 3.94–4.03 (m, 1H, H-6aglu), 4.06–4.18 (m, 2H, H-5glu, H-6bglu), 4.87 (dd-t,

Molecules 2019, 24, 4181
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J = 9.4 Hz, J = 10.4 Hz, H-4glu), 4.92 (dd-t, J = 9.7 Hz, J = 9.8 Hz, H-2glu), 5.15 and 5.21 (qAB, 2H, J
= 16.5 Hz, CH2CO), 5.33–5.48 (m, 4H, H-1glu, H-3glu, CH2Ochin), 7.38 (dd, 1H, J = 1.6 Hz, J = 7.5 Hz,
H-7chin), 7.41 (d, 1H, J = 8.4 Hz, H-3chin), 7.43 (dd, 1H, J = 7.5 Hz, J = 8.0 Hz, H-6chin), 7.47 (dd, 1H, J =
1.6 Hz, J = 8.0 Hz, H-5chin), 8.18 (d, 1H, J = 8.4 Hz, H-4chin), 8.24 (s, 1H, H-5triaz), 9.25 (d, 1H, J = 9.3 Hz,
CONH); 13C NMR (100 MHz, DMSO-d6):
δ 20.21, 20.24, 20.27, 20.41, 24.85, 51.34, 61.53, 67.65, 70.51,
72.06, 72.57, 76.78, 79.06, 110.09, 119.72, 122.38, 125.54, 126.38, 127.27, 135.85, 139.11, 142.37, 153.27,
157.15, 166.10, 169.06, 169.19, 169.37, 169.87; HRMS (ESI-TOF): calcd for C29H34N5O11 ([M + H]+): m/z
628.2255; found: m/z 628.2256.
Glycoconjugate 80: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-galactopyranosyl)azidoacetamide 34
, product was obtained as a pink solid (244.8 mg, 78%);
= 11.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
δ 1.92, 1.98, 1.99, 2.12
D
and 2-methyl-8-(2-propyn-1-yloxy)quinoline
4
27
m.p.: 98–101 ◦C; [
α
]
(4s, 12H, CH3CO), 2.63 (s, 3H, CH3), 3.98 (dd, 1H, J = 6.6 Hz, J = 11.3 Hz, H-6agal), 4.06 (dd, 1H, J =
5.9 Hz, J = 11.3 Hz, H-6bgal), 4.35 (m, 1H, H-5gal,), 5.07 (dd-t, 1H, J = 9.4 Hz, J = 9.4 Hz, H-2gal), 5.12
and 5.20 (qAB, 2H, J = 16.5 Hz, CH2CO), 5.26–5.44 (m, 5H, H-1gal, H-3gal, H-4gal, CH2Ochin), 7.32–7.54
(m, 4H, H-3chin, H-5chin, H-6chin, H-7chin)8.21 (d, 1H, J = 7.9 Hz, H-4chin), 8.24 (s, 1H, H-5triaz), 9.33 (d,
1H, J = 9.5 Hz, CONH); 13C NMR (100 MHz, DMSO-d6):
δ 20.23, 20.26, 20.31, 20.40, 24.84, 51.30, 61.54,
67.47, 68.16, 70.59, 71.35, 77.14, 79.06, 110.10, 119.72, 122.36, 125.54, 126.38, 127.24, 135.85, 139.11, 142.36,
153.27, 157.15, 166.02, 169.23, 169.29, 169.71, 169.77; HRMS (ESI-TOF): calcd for C29H34N5O11 ([M +
H]+): m/z 628.2255; found: m/z 628.2253.
Glycoconjugate 81: Starting from N-(
yloxy)quinoline
16.7 (c = 2.0, DMSO); 1H NMR (400 MHz, DMSO-d6):
β
-D-glucopyranosyl)azidoacetamide 35 and 8-(2-propyn-1-
25
3
, product was obtained as a brown solid (133.6 mg, 60%); m.p.: 160-163 ◦C; [
α
]
=
D
δ
3.04–3.15 (m, 3H, H-2glu, H-4glu, H-5glu), 3.21
(dd-t, 1H, J = 8.4 Hz, J = 8.6 Hz, H-3glu), 3.42 (m, 1H, H-6aglu), 3.63 (m, 1H, H-6bglu), 4.00–4.50 (m, 4H,
OH), 4.71 (dd-t, 1H, J = 8.9 Hz, J = 9.0 Hz, H-1glu), 5.17 and 5.22 (qAB, 2H, J = 16.5 Hz, CH2CO), 5.57 (s,
2H, CH2Ochin), 7.60–8.10 (m, 5H, H-3chin, H-4chin, H-5chin, H-6chin, H-7chin), 8.39 (s, 1H, H-5triaz), 8.96
(d, 1H, J = 7.4 Hz, H-2chin), 9.04 (d, 1H, J = 8.8 Hz, CONH); 13C NMR (100 MHz, DMSO-d6):
δ 51.55,
60.72, 62.36, 69.74, 72.44, 77.18, 78.65, 79.63, 112.94, 120.36, 122.56, 126.79, 128.94, 132.86, 136.25, 136.88,
141.50, 146.25, 151.30, 165.67; HRMS (ESI-TOF): calcd for C20H24N5O7 ([M + H]+): m/z 446.1676; found:
m/z 446.1679.
Glycoconjugate 82: Starting from N-(
yloxy)quinoline
14.5 (c = 2.0, DMSO); 1H NMR (400 MHz, DMSO-d6):
β
-D-galactopyranosyl)azidoacetamide 36 and 8-(2-propyn-1-
25
3
, product was obtained as a brown solid (129.2 mg, 58%); m.p.: 170-173 ◦C; [
α
]
=
D
δ
3.34 (dd, 1H, J = 3.2 Hz, J = 9.4 Hz, H-3gal),
3.36–3.46 (m, 3H, H-2gal, H-5gal, H-6agal), 3.50 (dd, 1H, J = 5.8 Hz, J = 10.5 Hz, H-6bgal), 3.69 (d,
1H, J = 3.0 Hz, H-4gal), 4.09–4.42 (m, 4H, OH), 4.69 (dd-t, 1H J = 8.9 Hz, J = 9.0 Hz, H-1gal), 5.18
(s, 2H, CH2CO), 5.60 (s, 2H, CH2Ochin), 7.56–8.16 (m, 4H, H-3chin, H-5chin, H-6chin, H-7chin), 8.41 (s,
1H, H-5triaz), 8.85–9.20 (m, 3H, H-2chin, H-4chin, CONH); 13C NMR (100 MHz, DMSO-d6):
δ 51.62,
60.31, 68.02, 69.66, 73.85, 76.75, 79.08, 80.07, 112.53, 120.38, 126.83, 126.96, 129.01, 130.10, 141.66, 142.90,
146.07, 150.24, 152.06, 165.58; HRMS (ESI-TOF): calcd for C20H24N5O7 ([M + H]+): m/z 446.1676; found:
m/z 446.1670.
Glycoconjugate 83: Starting from N-(
β
-D-glucopyranosyl)azidoacetamide 35 and 2-methyl-8-(2-
, product was obtained as a brown solid (140.1 mg, 61%); m.p.: 135–138
2.8 (c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
= δ 2.92 (s, 3H, CH3), 3.04–3.24 (m,
propyn-1-yloxy)quinoline
4
26
◦C; [
α
]
−
D
3H, H-2glu, H-4glu, H-5glu), 3.39–3.47 (m, 2H, H-3glu, H-6aglu,), 3.62 (dd, 1H, J = 1.6 Hz, J = 12.1 Hz,
H-6bglu), 4.69 (dd-t, 1H, J = 8.9 Hz, J = 9.0 Hz, H-1glu), 5.15 and 5.20 (qAB, 2H, J = 16.5 Hz, CH2CO),
5.60 (s, 2H, CH2Ochin), 7.73–7.93 (m, 4H, H-3chin, H-5chin, H-6chin, H-7chin), 8.34 (s, 1H, H-5triaz), 8.89 (d,
1H, J = 8.3 Hz, H-4chin), 9.04 (d, 1H, J = 8.8 Hz, CONH); 13C NMR (100 MHz, DMSO-d6):
δ
18.45, 51.52,
60.71, 62.31, 69.74, 72.42, 77.18, 78.65, 79.62, 113.85, 120.30, 124.31, 126.87, 127.70, 128.48, 141.31, 143.79,

Molecules 2019, 24, 4181
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148.61, 158.29, 163.67, 165.65; HRMS (ESI-TOF): calcd for C21H26N5O7 ([M + H]+): m/z 460.1832; found:
m/z 460.1830.
Glycoconjugate 84: Starting from N-(
β
-D-galactopyranosyl)azidoacetamide 36 and 2-methyl-8-(2-
, product was obtained as a brown solid (179.2 mg, 78%); m.p.: 145–148 ◦C;
= 5.0 (c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
δ 2.88 (s, 3H, CH3), 3.34 (dd, 1H, J =
D
propyn-1-yloxy)quinoline
4
24
[
α
]
3.2 Hz, J = 9.4 Hz, H-3gal), 3.37-3.54 (m, 4H, H-2gal, H-5gal, H-6agal, H-6bgal), 3.69 (d, 1H, J = 3.0 Hz,
H-4gal), 3.95–4.31 (m, 4H, OH), 4.67 (dd-t, 1H, J = 8.9 Hz, J = 9.0 Hz, H-1gal), 5.17 (s, 2H, CH2CO), 5.59
(s, 2H, CH2Ochin), 7.62–7.98 (m, 4H, H-3chin, H-5chin, H-6chin, H-7chin), 8.34 (s, 1H, H-5triaz), 8.84 (bs,
1H, H-4chin), 9.01 (d, 1H, J = 9.0 Hz, CONH); 13C NMR (100 MHz, DMSO-d6):
δ 18.45, 51.55, 60.30,
62.27, 68.01, 69.65, 73.85, 76.74, 80.06, 113.46, 120.27, 124.12, 126.87, 128.23, 131.53, 141.40, 142.91, 149.12,
158.22, 162.36, 165.59; HRMS (ESI-TOF): calcd for C21H26N5O7 ([M + H]+): m/z 460.1832; found: m/z
460.1831.
Glycoconjugate 85: Starting from 2,3,4,6-tetra-O-acetyl-N-(β-D-glucopyranosyl)propiolamide 37 and
8-(2-azidoethoxy)quinoline
5
, product was obtained as a yellow solid (220.9 mg, 72%); m.p.: 89–94 ◦C;
23
1
[
α
]
=
−
18.0 (c = 1.0, CHCl3); H NMR (400 MHz, DMSO-d6):
δ
1.86, 1.94, 1.98, 2.00 (4s, 12H,
D
CH3CO), 3.98 (dd, 1H, J = 3.9 Hz, J = 14.0 Hz, H-6aglu), 4.07–4.18 (m, 2H, H-5glu, H-6bglu), 4.66 (t,
2H, J = 5.1 Hz, CH2N), 4.90 (dd-t, 1H, J = 9.6 Hz, J = 9.6 Hz, H-4glu), 4.98 (t, 2H, J = 5.1 Hz, CH2O),
5.20 (dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-2glu), 5.38 (dd-t, 1H, J = 9.5 Hz, J = 9.5 Hz, H-1glu), 5.59 (dd-t,
1H, J = 9.3 Hz, J = 9.4 Hz, H-3glu), 7.25 (dd, 1H, J = 1.4 Hz, J = 7.5 Hz, H-7chin), 7.47–7.59 (m, 3H,
H-3chin, H-5chin, H-6chin), 8.32 (dd, 1H, J = 1.7 Hz, J = 8.4 Hz, H-4chin), 8.87 (dd, 1H, J = 1.5 Hz, J =
4.1 Hz, H-2chin), 8.98 (s, 1H, H-5triaz), 9.20 (d, 1H, J = 9.5 Hz, NHCO); 13C NMR (100 MHz, DMSO-d6):
δ
20.30, 20.31, 20.37, 20.50, 49.56, 61.85, 67.07, 67.85, 70.49, 72.04, 73.03, 76.79, 110.69, 120.60, 121.93,
126.69, 128.20, 129.08, 135.86, 139.71, 141.83, 149.25, 153.60, 160.03, 169.02, 169.32, 169.54, 169.97; HRMS
(ESI-TOF): calcd for C28H32N5O11 ([M + H]+): m/z 614.2098; found: m/z 614.2097.
Glycoconjugate 86: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-galactopyranosyl)propiolamide 38 and
, product was obtained as a white solid (285.3 mg, 93%); m.p.: 187–189 ◦C;
6.8 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
= δ 1.96, 2.00, 2.01, 2.17 (4s, 12H, CH3CO),
8-(2-azidoethoxy)quinoline
5
24
[
α
]
−
D
4.03–4.17 (m, 3H, H-5gal, H-6agal, H-6bgal), 4.63 (t, 2H, J = 4.9 Hz, CH2N), 5.02 (t, 2H, J = 4.9 Hz, CH2O),
5.15 (dd, 1H, J = 3.3 Hz, J = 10.1 Hz, H-3gal), 5.30 (dd-t, 1H, J = 9.3 Hz, J = 10.1 Hz, H-2gal), 5.41 (dd-t,
1H, J = 9.3 Hz, J = 9.5 Hz, H-1gal), 5.45 (dd, 1H, J = 0.6 Hz, J = 3.3 Hz, H-4gal), 7.04 (dd, 1H, J = 1.7 Hz, J
= 7.2 Hz, H-7chin), 7.40–7.50 (m, 3H, H-3chin, H-5chin, H-6chin), 7.83 (d, 1H, J = 9.5 Hz, NHCO); 8.14 (dd,
1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.95 (s, 1H, H-5triaz), 9.00 (dd, 1H, J = 1.7 Hz, J = 4.2 Hz. H-2chin);
13C NMR (100 MHz, CDCl3):
δ 20.57, 20.63, 20.64, 20.67, 50.14, 61.27, 67.24, 67.53, 68.08, 71.17, 72.32,
78.15, 110.28, 121.34, 122.02, 126.42, 128.22, 129.64, 135.98, 140.36, 142.35, 149.81, 153.67, 160.32, 169.90,
170.15, 170.35, 170.46; HRMS (ESI-TOF): calcd for C28H32N5O11 ([M + H]+): m/z 614.2098; found: m/z
614.2095.
Glycoconjugate 87: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-glucopyranosyl)propiolamide 37 and
, product was obtained as a yellow solid (207.1 mg, 66%); m.p.:
14.8 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.85, 1.93, 1.98, 2.00 (4s,
2-methyl-8-(2-azidoethoxy)quinoline
8
24
167–172 ◦C; [
α
]
−
D
12H, CH3CO), 2.72 (s, 3H, CH3), 3.98 (dd, 1H, J = 4.5 Hz, J = 14.3 Hz, H-6aglu), 4.07–4.18 (m, 2H, H-5glu
,
H-6bglu), 4.54–4.67 (m, 2H, CH2N), 4.90 (dd-t, 1H, J = 9.4 Hz, J = 9.5 Hz, H-4glu), 4.98 (t, 2H, J = 5.0 Hz,
CH2O), 5.21 (dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-2glu),5.38 (dd-t, 1H, J = 9.5 Hz, J = 9.5 Hz, H-1glu), 5.60
(dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-3glu), 7.21 (dd, 1H, J = 1.2 Hz, J = 7.7 Hz, H-7chin), 7.38–7.46 (m, 2H,
H-3chin, H-6chin), 7.50 (dd, 1H, J = 1.1 Hz, J = 8.2 Hz, H-5chin), 8.20 (d, 1H, J = 8.5, H-4chin), 9.17 (d, 1H, J
= 9.5 Hz, NHCO), 9.20 (s, 1H, H-5triaz); 13C NMR (100 MHz, DMSO-d6):
δ 20.29, 20.31, 20.37, 20.50,
25.00, 49.59, 61.86, 67.17, 67.85, 70.52, 72.01, 73.01, 76.75, 111.06, 120.46, 122.58, 125.63, 127.30, 128.62,
136.02, 139.28, 141.93, 153.06, 157.80, 160.08, 169.01, 169.32, 169.53, 169.97; HRMS (ESI-TOF): calcd for
C29H33N5O11 ([M + H]+): m/z 628.2255; found: m/z 628.2252.

Molecules 2019, 24, 4181
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Glycoconjugate 88: Starting from 2,3,4,6-tetra-O-acetyl-N-(β-D-galactopyranosyl)propiolamide 38 and
2-methyl-8-(2-azidoethoxy)quinoline
8
, product was obtained as a white solid (257.3 mg, 82%); m.p.:
25
107–109 ◦C; [
α
]
= δ 1.95, 2.00, 2.02, 2.17 (4s, 12H,
−
7.2 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
D
CH3CO), 2.88 (s, 3H, CH3), 4.03–4.17 (m, 3H, H-5gal, H-6agal, H-6bgal), 4.59 (t, 2H, J = 4.9 Hz, CH2N),
5.00 (t, 2H, J = 4.8 Hz, CH2O), 5.15 (dd, 1H, J = 3.4 Hz, J = 10.2 Hz, H-3gal), 5.30 (dd-t, 1H, J = 9.4 Hz, J
= 10.2 Hz, H-2gal), 5.42 (dd-t, 1H, J = 9.4 Hz, J = 9.5 Hz, H-1gal), 5.45 (dd, 1H, J = 0.7 Hz, J = 3.4 Hz,
H-4gal), 7.02 (dd, 1H, J = 1.3 Hz, J = 7.5 Hz, H-7chin), 7.32–7.39 (m, 2H, H-3chin, H-6chin), 7.42 (dd, 1H, J
= 1.3 Hz, J = 8.2 Hz, H-5chin), 7.84 (d, 1H, J = 9.6 Hz, NHCO), 8.02 (d, 1H, J = 8.4 Hz, H-4chin), 9.26 (s,
1H, H-5triaz); 13C NMR (100 MHz, CDCl3):
δ 20.57, 20.61, 20.64, 20.66, 25.62, 50.18, 61.23, 67.23, 67.45,
68.08, 71.18, 72.25, 78.11, 110.54, 121.14, 122.90, 125.38, 127.79, 128.65, 136.04, 139.94, 142.40, 153.15,
159.03, 160.36, 169.90, 170.15, 170.34, 170.41; HRMS (ESI-TOF): calcd for C29H34N5O11 ([M + H]+): m/z
628.2255; found: m/z 628.2254.
Glycoconjugate 89: Starting from N-(
quinoline
= 1.0, DMSO); 1H NMR (400 MHz, DMSO-d6):
β
-D-glucopyranosyl)propiolamide 39 and 8-(2-azidoethoxy)
28
5
, product was obtained as a white solid (133.6 mg, 60%); m.p.: 169–171 ◦C; [
α
]
D = 5.0 (c
δ
3.05-3.11 (m, 1H, H-5glu), 3.13–3.18 (m, 2H, H-2glu,
H-4glu), 3.33–3.37 (m, 1H, H-3glu), 3.38–3.44 (m, 1H, H-6aglu), 3.60–3.67 (m, 1H, H-6bglu), 4.48 (t, 1H,
J = 5.9 Hz, 6-OH), 4.66 (t, 2H, J = 4.6 Hz, CH2N), 4.83–4.93 (m, 3H, H-1glu, OH), 4.95–5.01 (m, 3H,
CH2O, OH), 7.25 (d, 1H, J = 7.5 Hz, H-7chin), 7.47–7.62 (m, 3H, H-3chin, H-5chin, H-6chin), 8.32 (d, 1H, J =
10.4 Hz, H-4chin), 8.68 (d, 1H, J = 9.1 Hz, NHCO), 8.88 (bs, 1H, H-2chin), 8.94 (s, 1H, H-5triaz); 13C NMR
(100 MHz, DMSO-d6):
δ 49.52, 60.97, 67.11, 69.97, 71.83, 77.44, 78.70, 79.51, 110.64, 120.60, 121.96, 126.69,
127.68, 129.08, 135.84, 139.71, 142.53, 149.29, 153.63, 160.08; HRMS (ESI-TOF): calcd for C20H24N5O7
([M + H]+): m/z 446.1676; found: m/z 446.1678.
Glycoconjugate 90: Starting from N-(
quinoline
1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
β
-D-galactopyranosyl)propiolamide 40 and 8-(2-azidoethoxy)
25
5
, product was obtained as a white solid (189.3 mg, 85%); m.p.: 162–164 ◦C; [
α
]
D = 24.8 (c =
δ
3.34-3.54 (m, 4H, H-2gal, H-3gal, H-4gal H-5gal), 3.57–3.65
(m, 1H, H-6agal), 3.66–3.72 (m, 1H, H-6bgal), 4.29 (d, 1H, J = 4.9 Hz, OH), 4.56 (t, 1H, J = 5.4, 6-OH), 4.66
(t, 2H, J = 5.1 Hz, CH2N), 4.74 (d, 1H, J = 5.5 Hz, OH), 4.79 (d, 1H, J = 5.5 Hz, OH), 4.87 (dd-t, 1H, J =
9.0 Hz, J = 9.1 Hz, H-1gal), 4.98 (t, 2H, J = 5.0 Hz, CH2O), 7.26 (dd, 1H, J = 1.4 Hz, J = 7.5 Hz, H-7chin),
7.47–7.59 (m, 3H, H-3chin, H-5chin, H-6chin), 8.32 (dd, 1H, J = 1.5 Hz, J = 8.2 Hz, H-4chin), 8.48 (d, 1H, J =
9.1 Hz, NHCO), 8.88 (dd, 1H, J = 1.7 Hz, J = 4.1 Hz, H-2chin), 8.95 (s, 1H, H-5triaz); 13C NMR (100 MHz,
DMSO-d6):
δ 49.52, 60.42, 67.13, 68.37, 69.33, 74.03, 76.82, 79.93, 110.69, 120.60, 121.93, 126.68, 127.61,
129.07, 135.84, 139.72, 142.47, 149.29, 153.62, 159.97; HRMS (ESI-TOF): calcd for C20H24N5O7 ([M +
H]+): m/z 446.1676; found: m/z 446.1675.
Glycoconjugate 91: Starting from N-(
β
-D-glucopyranosyl)propiolamide 39 and 2-methyl-8-(2-
, product was obtained as a white solid (144.7 mg, 63%); m.p.: 159–161 ◦C;
3.6 (c = 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6):
= δ 2.72 (s, 3H, CH3), 3.03–3.12 (m, 1H,
azidoethoxy)quinoline
8
25
[α
]
−
D
H-5glu), 3.13–3.27 (m, 2H, H-2glu, H-4glu), 3.34–3.46 (m, 2H, H-3glu, H-6aglu), 3.60–3.68 (m, 1H, H-6bglu),
4.47 (t, 1H, J = 5.9 Hz, 6-OH), 4.55–4.67 (m, 2H, CH2N), 4.86–4.93 (m, 3H, H-1glu, OH), 4.94–5.02 (m,
3H, CH2O, OH), 7.21 (dd, 1H, J = 1.2 Hz, J = 7.7 Hz, H-7chin), 7.39–7.47 (m, 2H, H-3chin, H-6chin), 7.50
(dd, 1H, J = 1.1 Hz, J = 8.2 Hz, H-5chin), 8.20 (d, 1H, J = 8.4 Hz, H-4chin), 8.63 (d, 1H, J = 9.1 Hz, NHCO),
9.15 (s, 1H, H-5triaz); 13C NMR (100 MHz, DMSO-d6):
δ 25.07, 49.57, 60.99, 67.27, 69.97, 71.85, 77.42,
78.68, 79.47, 111.02, 120.47, 122.62, 125.64, 127.31, 128.11, 136.02, 139.28, 142.63, 153.11, 157.85, 160.12;
HRMS (ESI-TOF): calcd for C20H24N5O7 ([M + H]+): m/z 460.1832; found: m/z 460.1830.
Glycoconjugate 92: Starting from N-(
β
-D-galactopyranosyl)propiolamide 40 and 2-methyl-8-(2-
, product was obtained as a white solid (186.1 mg, 81%); m.p.: 148–151 ◦C;
2.72 (s, 3H, CH3), 3.34–3.55 (m, 4H,
azidoethoxy)quinoline
8
28
[
α
]
D = 23.0 (c = 1.0, DMSO); 1H NMR (400 MHz, DMSO-d6):
δ
H-2gal, H-3gal, H-4gal H-5gal), 3.57–3.66 (m, 1H, H-6agal), 3.66–3.72 (m, 1H, H-6bgal), 4.28 (d, 1H, J =
5.0 Hz, OH), 4.52–4.67 (m, 3H, CH2N, 6-OH), 4.73 (d, 1H, J = 5.5 Hz, OH), 4.79 (d, 1H, J = 5.5 Hz, OH),

Molecules 2019, 24, 4181
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4.88 (dd-t, 1H, J = 9.0 Hz, J = 9.1 Hz, H-1gal), 4.98 (t, 2H, J = 5.0 Hz, CH2O), 7.21 (dd, 1H, J = 1.2 Hz, J =
7.7 Hz, H-7chin), 7.39–7.46 (m, 2H, H-3chin, H-6chin), 7.50 (dd, 1H, J = 1.1 Hz, J = 8.2 Hz, H-5chin), 8.20
(d, 1H, J = 8.4 Hz, H-4chin), 8.43 (d, 1H, J = 9.1 Hz, NHCO), 9.16 (s, 1H, H-5triaz); 13C NMR (100 MHz,
DMSO-d6):
δ 25.04, 49.56, 60.40, 67.28, 68.37, 69.36, 74.02, 76.78, 79.89, 111.08, 120.47, 122.59, 125.62,
127.30, 128.04, 136.00, 139.29, 142.57, 153.11, 157.83, 160.00; HRMS (ESI-TOF): calcd for C21H26N5O7
([M + H]+): m/z 460.1832; found: m/z 460.1836.
Glycoconjugate 93: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-glucopyranosyl)propiolamide 37 and
, product was obtained as a yellow solid (210.2 mg, 67%); m.p.:
18.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.89, 1.94, 1.99, 2.00 (4s,
8-(3-azidopropoxy)quinoline
6
24
178–180 ◦C; [
α
]
−
D
12H, CH3CO), 2.40–2.50 (m, 2H, CH2), 4.00 (dd, 1H, J = 4.4 Hz, J = 14.2 Hz, H-6aglu), 4.06–4.18 (m, 2H,
H-5glu, H-6bglu), 4.21 (t, 2H, J = 6.0 Hz, CH2N), 4.72 (t, 2H, J = 6.8 Hz, CH2O), 4.91 (dd-t, 1H, J = 9.5 Hz,
J = 9.5 Hz, H-4glu), 5.21 (dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-2glu), 5.39 (dd-t, 1H, J = 9.5 Hz, J = 9.5 Hz,
H-1glu), 5.61 (dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-3glu), 7.20 (dd, 1H, J = 1.8 Hz, J = 7.1 Hz, H-7chin),
7.46–7.59 (m, 3H, H-3chin, H-5chin, H-6chin), 8.32 (dd, 1H, J = 1.5 Hz, J = 8.1 Hz, H-4chin), 8.90 (dd, 1H, J
= 1.7 Hz, J = 4.0 Hz, H-2chin), 8.90 (s, 1H, H-5triaz), 9.17 (d, 1H, J = 9.5 Hz, NHCO); 13C NMR (100 MHz,
DMSO-d6):
δ 20.32, 20.33, 20.38, 20.52, 29.36, 47.24, 61.85, 65.52, 67.84, 70.52, 72.04, 73.02, 76.80, 109.92,
119.97, 121.84, 126.77, 127.67, 129.03, 135.79, 139.77, 141.83, 149.07, 154.18, 160.10, 169.04, 169.32, 169.54,
169.98; HRMS (ESI-TOF): calcd for C29H34N5O11 ([M + H]+): m/z 628.2255; found: m/z 628.2252.
Glycoconjugate 94: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-galactopyranosyl)propiolamide 38 and
, product was obtained as a white solid (263.6 mg, 84%); m.p.: 98–100 ◦C;
5.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
= δ 1.99, 2.00, 2.03, 2.17 (4s, 12H, CH3CO),
8-(3-azidopropoxy)quinoline
6
25
[
α
]
−
D
2.62 (p, 2H, J = 6.2 Hz, CH2), 4.04–4.18 (m, 3H, H-5gal, H-6agal, H-6bgal), 4.24 (t, 2H, J = 5.8 Hz, CH2N),
4.81 (t, 2H, J = 6.6 Hz, CH2O), 5.17 (dd, 1H, J = 3.3 Hz, J = 10.2 Hz, H-3gal), 5.31 (dd-t, 1H, J = 9.4 Hz, J
= 10.2 Hz, H-2gal), 5.42 (dd-t, 1H, J = 9.4 Hz, J = 9.5 Hz, H-1gal), 5.46 (dd, 1H, J = 0.6 Hz, J = 3.3 Hz,
H-4gal), 7.06 (dd, 1H, J = 1.7 Hz, J = 7.2 Hz, H-7chin), 7.41–7.50 (m, 3H, H-3chin, H-5chin, H-6chin), 7.85 (d,
1H, J = 9.5 Hz, NHCO), 8.16 (dd, 1H, J = 1.7 Hz, J = 8.3 Hz, H-4chin), 8.52 (s, 1H, H-5triaz), 9.01 (dd, 1H,
J = 1.7 Hz, J = 4.2 Hz. H-2chin); 13C NMR (100 MHz, CDCl3):
δ 20.53, 20.57, 20.64, 20.68, 29.67, 47.73,
61.28, 65.36, 67.24, 68.11, 71.16, 72.33, 78.16, 109.94, 120.67, 121.82, 126.62, 127.18, 129.61, 136.09, 140.39,
142.04, 149.55, 154.23, 160.36, 169.90, 170.15, 170.36, 170.45; HRMS (ESI-TOF): calcd for C29H34N5O11
([M + H]+): m/z 628.2255; found: m/z 628.2253.
Glycoconjugate 95: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-glucopyranosyl)propiolamide 37 and
, product was obtained as a beige solid (195.7 mg, 61%); m.p.:
18.0 (c = 1.0, CHCl3); 1H NMR (400 MHz, DMSO-d6):
= δ 1.88, 1.94, 1.99, 2.00 (4s,
2-methyl-8-(3-azidopropoxy)quinoline
9
24
197–198 ◦C; [
α
]
−
D
12H, CH3CO), 2.41–2.49 (m, 2H, CH2), 2.67 (s, 3H, CH3), 3.96–4.02 (m, 1H, H-6aglu), 4.05–4.17 (m, 2H,
H-5glu, H-6bglu), 4.20 (t, 2H, J = 6.2 Hz, CH2N), 4.71 (t, 2H, J = 6.9 Hz, CH2O), 4.91 (dd-t, 1H, J = 9.5 Hz,
J = 9.5 Hz, H-4glu), 5.20 (dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-2glu), 5.38 (dd-t, 1H, J = 9.5 Hz, J = 9.5 Hz,
H-1glu), 5.59 (dd-t, 1H, J = 9.3 Hz, J = 9.4 Hz, H-3glu), 7.17 (dd, 1H, J = 1.3 Hz, J = 7.6 Hz, H-7chin),
7.36–7.44 (m, 2H, H-3chin, H-6chin), 7.47 (dd, 1H, J = 1.2 Hz, J = 8.2 Hz, H-5chin), 8.19 (d, 1H, J = 8.4 Hz,
H-4chin), 8.83 (s, 1H, H-5triaz), 9.17 (d, 1H, J = 9.5 Hz, NHCO); 13C NMR (100 MHz, DMSO-d6):
δ 20.31,
20.37, 20.51, 20.74, 25.03, 29.25, 47.14, 61.84, 65.56, 67.83, 70.51, 72.02, 73.01, 76.78, 110.54, 119.91, 122.44,
125.68, 127.32, 127.58, 135.97, 139.34, 141.77, 153.64, 157.35, 160.06, 169.02, 169.31, 169.53, 169.97; HRMS
(ESI-TOF): calcd for C30H36N5O11 ([M + H]+): m/z 642.2411; found: m/z 642.2408.
Glycoconjugate 96: Starting from 2,3,4,6-tetra-O-acetyl-N-(
β
-D-galactopyranosyl)propiolamide 38 and
, product was obtained as a white solid (202.1 mg, 63%); m.p.:
4.6 (c = 1.0, CHCl3); 1H NMR (400 MHz, CDCl3):
= δ 1.98, 2.00, 2.03, 2.17 (4s, 12H,
2-methyl-8-(3-azidopropoxy)quinoline
9
25
121–123 ◦C; [
α
]
−
D
CH3CO), 2.60 (p, 2H, J = 6.4 Hz, CH2), 2.80 (s, 3H, CH3), 4.04–4.17 (m, 3H, H-5gal, H-6agal, H-6bgal),
4.24 (t, 2H, J = 5.9 Hz, CH2N), 4.82 (t, 2H, J = 6.7 Hz, CH2O), 5.16 (dd, 1H, J = 3.4 Hz, J = 10.2 Hz,
H-3gal), 5.30 (dd-t, 1H, J = 9.4 Hz, J = 10.1 Hz, H-2gal), 5.40 (dd-t, 1H, J = 9.4 Hz, J = 9.5 Hz, H-1gal), 5.46