CuAAC mediated synthesis of cyclen cored glycodendrimers of high sugar tethers at low generation

Article abstract of DOI:10.1016/j.carres.2021.108403

Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, pharmaceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems. Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to produce a variety of novel 12–sugar coated (G₀) glycodendrimers 12-15 adorn with β-Glc-, β-Man-, β-Gal-, β-Lac, along with 36-galactose coated (G₁) glycodendrimer 18 in good-to-high yield. The structures of the developed glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR (¹H & ¹³CNMR), HRMS, MALDI-TOF MS, UV–Vis, IR, and SEC (Size Exclusion Chromatogram) data.

Full text of DOI:10.1016/j.carres.2021.108403

Carbohydrate Research 508 (2021) 108403
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
CuAAC mediated synthesis of cyclen cored glycodendrimers of high sugar
tethers at low generation☆
Anand K. Agrahari, Manoj K. Jaiswal, Mangal S. Yadav, Vinod K. Tiwari*
Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India
A R T I C L E I N F O
A B S T R A C T
Keywords:
Glycodendrimers are receiving considerable attention to mimic a number of imperative features of cell surface
glycoconjugate and acquired excellent relevance to a wide domain of investigations including medicine, phar-
maceutics, catalysis, nanotechnology, carbohydrate-protein interaction, and moreover in drug delivery systems.
Toward this end, an expeditious, modular, and regioselective triazole-forming CuAAC click approach along with
double stage convergent synthetic method was chosen to develop a variety of novel chlorine-containing cyclen
cored glycodendrimers of high sugar tethers at low generation of promising therapeutic potential. We developed
a novel chlorine-containing hypercore unit with 12 alkynyl functionality originated from cyclen scaffold which
was confirmed by its single crystal X-ray data analysis. Further, the modular CuAAC technique was utilized to
produce a variety of novel 12–sugar coated (G0) glycodendrimers 12-15 adorn with β-Glc-, β-Man-, β-Gal-, β-Lac,
along with 36-galactose coated (G1) glycodendrimer 18 in good-to-high yield. The structures of the developed
glycodendrimer architectures have been well elucidated by extensive spectral analysis including NMR (1H &
13CNMR), HRMS, MALDI-TOF MS, UV–Vis, IR, and SEC (Size Exclusion Chromatogram) data.
CuAAC
Click chemistry
Cyclen
Glycodendrimer
Multivalency
Triazole
1. Introduction
other class of multivalent glycoclusters due to their high mono-
dispersity, possibility to organize their size and multiple sugar units at
Several biological processes such as, cellular adhesion, pathogen
invasion, toxin hormone mediation, fertilization, and cell recognition is
greatly depend on the multiple carbohydrate-protein interactions [1–8].
In nature, the low affinity and specificity of monosaccharide ligand can
be circumvent by adopting the multivalency [9,10]. Thus, the glyco-
cluster effect has opened up the opportunity of promoting and/or
inhibiting the carbohydrate protein interaction with synthetic multiva-
lent glycoconjugates [11,12]. Carbohydrates are the integral part of the
living system which firmly responsible for the intercellular and intra-
cellular interaction [13–15]. In addition, the great structural diversity of
the end [23–30]. Macrocyclic polyamines are now frequently used as
carriers of radionuclides in single photon emission computed tomogra-
phy (SPECT), positron emission tomography (PET), and radio-immuno
therapy (RIT) [31]. These versatility of macrocycles (cyclens) towards
N-functionalization offer selective coordination for a plethora of metal
ions [32,33]. For instance, selective extraction of Cu(II) ions from
biocompatible environment by 1,4,7,10-tetraazacyclododecane tetra-
acetic acid (DOTA)- functionalized poly(propyleneimine) (PPI) glyco-
dendrimers [34]. On the contrary, few researchers have also designed
N-acetylgalactosamino dendron-clearing agent derived from DOTA and
studied its effectiveness against DOTA-based pretargeted radio-
immunotherapy (DOTA-PRIT) [35,36]. Apart from this, cyclen systems
possess high thermodynamic and kinetic stability and displayed profuse
application within biomimetic systems, as catalyst, as a fluorescent
probe and in biomedicine [37]. Thereby, in order to construct a
hypercore, N-tetra-alkylation of cyclen facilitates a remarkable modifi-
cation in the macrocycles [38,39]. A number of different chemical
ligation techniques, like amide formation [40], carbamates [41],
carbohydrates like functional groups, linkages (α- or β-), as well the ring
systems (pyranose or furanose form), along with several other signifi-
cant features, such as, biocompatibility, hydrophilicity, minimal
toxicity, and superior ADME properties inspired not only the synthetic
chemists but also the medicinal chemists to design the diverse multi-
valent glycocluster architectures specifically glycopolymers, glycoden-
drimers, neoglycoproteins, or glyconanoparticles [16–22]. Among
these, the glycodendrimers have attracted greater attention than the
☆
This manuscript is dedicated to Prof. (em.) Richard R. Schmidt at Universitat Konstanz, Germany on the occasion of celebration of his 87th birthday anniversary.
* Corresponding author.
E-mail addresses: tiwari_chem@yahoo.co.in, Vinod.Tiwari@bhu.ac.in (V.K. Tiwari).
https://doi.org/10.1016/j.carres.2021.108403
Received 4 June 2021; Received in revised form 12 July 2021; Accepted 19 July 2021
Available online 24 July 2021
0008-6215/© 2021 Elsevier Ltd. All rights reserved.

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
thiourea [42], oxime ligation [43], reductive amination [44],
Pd-mediated Sonogashira [45], cycloaddition reactions [46], thiol-yne
coupling [47], etc. were successfully used to construct the
well-defined glycodendrimer architectures. Among which, copper
(I)-catalyzed azide/alkyne cycloaddition ‘CuAAC’ reaction is the most
efficient, versatile, reliable, regioselective, high-yielding and modular
tool [48,49]. Thus, the Sharpless-Meldal ‘CuAAC’ tool [50] extensively
exploited for the successful construction of regioselective 1,4-disubsti-
tuted 1,2,3-triazole linked dendritic carbohydrate architectures with
great ease [48]. It is evident from the literature that the high-affinity
protein-ligand interactions have large utility in disease diagnosis, pre-
vention, and treatment [51]. Thus, a promising tool to achieve such
scaffold is the generation of multivalent moiety that interacts to multi-
valent target. A very few literatures are available to construct such a
highly functional glycodendrimer at the lowest possible generation [52,
53]. The remarkable advantage of such type of glycodendrimer is the
high functional group density at the low generation which opens a new
area for the interaction of molecule with the surrounding protein
[52–54]. Within the framework of these criteria, we designed and
developed a chlorine-containing hypercore unit having 12 alkynyl
functionality at its outer surface derived from cyclen scaffold diver-
gently. Initially, cyclen cored glycodendrimers (G0) adorned with
various sugars (Glc, Man, Gal, and Lac) were synthesized. Next, the
chlorine containing dendritic wedge was directly grafted over the
hypercore to provide a 36-galactose coated dendrimer at lowest possible
generation (G1) using the modular click tool.
Scheme 1. The construction of alkynyl functionalized compound 3 and 1,3-
dichloro-2-(chloromethyl)-4,5,6-tris(propargyloxy)benzene 4.
implemented reaction conditions were optimized (Table 1).
In this optimization, 3,4,5-tris(propargyloxy)benzene methanol 3,
and sulfuryl chloride (SO2Cl2) were taken as the starting substrates,
stirred at room temperature in various reaction conditions to produce
the desired 1,3-dichloro-2-(chloromethyl)-4,5,6-tris(propargyloxy)ben-
zene 4 as the product. Initially, 3,4,5-tris (propargyloxy)phenyl meth-
anol 3 (1.0 equiv.), SO2Cl2 (3.0 equiv.) were taken in reaction vessel
already having dichloromethane at room temperature, and stirred for
15 min which resulted compound 4 with <20% yield (Table 1, entry 1).
After achieving the targeted product, the reaction was optimized by
varying the parameters like solvents, equivalent of SO2Cl2 used and also
the reaction time. In this regard, the reaction was optimized in different
solvents like DCM, DMF, THF, DCE, and acetone. Further, the reaction
was carried out in the absence of solvent by increasing the equivalent of
SO2Cl2 (12.0 equiv), the yield of compound 4 was found to be 60%
(Table 1, entry 7), which inferred that, the solvent was not necessary to
proceed the reaction. Thus, the best result was obtained when the
compound 3 (1.0 equiv.) was treated with SO2Cl2 (12.0 equiv), at rt for
30 min (Table 1, entry 8). Finally, the developed compound 4 was well
elucidated by 1H NMR, the disappearance of peak at δ 6.75 ppm inferred
the C–H functionalization by chlorine at position 1 and 3, which was
further substantiated by the 13C NMR and HRMS spectroscopy.
After the successful synthesis and complete spectral elucidation of
novel 1,3-dichloro-2-(chloromethyl)-4,5,6-tris(propargyloxy)benzene 4,
it was treated with cyclen azamacrocycle 5, in order to build a 12
alkynyl novel hypercore 6 in 70% yield (Scheme 2). The synthesized
architecture was well elucidated by NMR, IR, HRMS and finally by
Single Crystal XRD data.
2. Results and discussion
To highlight the multivalency for the remarkable carbohydrate-
lectin interaction, we designed the synthesis of cyclen cored 36-galac-
tose coated glycodendrimer (G1) along with glycodendrimer (G0) hav-
ing variety of sugar unit as end groups namely (Glc, Gal, Man and Lac)
using regioselective Cu(I)-catalyzed azide-alkyne click reaction. There
are only few literatures available on the concept of cyclen based den-
drimers [55]. As we know, aromatic ‘aglycones’ have played a pivotal
role in π-π stacking interaction, so, the tris-propargyloxy benzoate den-
dron was selected as potential AB3 branching unit [56]. Thus, for the
successful development of (G0) and (G1) generation cyclen cored gly-
codendrimer of high sugar tethers at low generation, a double stage
convergent method was adapted [57]. The overall schematic plan in-
cludes, the synthesis of alkynyl functionalized cyclen based hypercore
divergently followed by incorporation of clickable azido sugars (Glc,
Gal, Man, and Lac) and finally coupled with galactose-conjugated den-
dritic scaffold to afford desired glycodendrimers. Thus in detail, our
synthesis commenced with the development of targeted hypercore. We
started our reaction with the commercially available trihydroxybenzoic
acid commonly known as gallic acid. In this regard, 3,4,5-tris-hydrox-
ybenzoic acid was esterified to 3,4,5-tris-hydroxybenzoate 1, which on
subsequently propargylated by reacting with propargyl bromide, in the
presence of K2CO3, 18-crown-6 ether (co-catalyst) in anhydrous acetone
to their respective propargyl derivative 2. Furthermore, the ester func-
tionality of tris-(propargyloxy)benzoate 2 was reduced to 3,4,5-tris
(propargyloxy)methanol 3 using LAH in anhydrous tetrahydrofuran at
room temperature for 4 h (Scheme 1). In 1H NMR, the two distinct
signals at δ 2.50 and 2.45 ppm were observed with ratio 2:1, which
displayed two chemically non-equivalent acetylenic-H in scaffold 3. It is
evidenced from the available literature; chlorinated scaffolds constitute
the family of compounds having high therapeutic potential [58]. Thus,
these findings encouraged us to design chlorine containing novel den-
dron and ultimately the novel chloro-containing cyclen cored
glycodendrimer.
After that, clickable 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide
8 [18], 2,3,4,6-tetra-O-acetyl, β-D-mannopyranosyl azide 9 [56], 2,3,4,
Table 1
Optimization to produce a chlorine functionalized dendron 4.[a]
.
Entry
Substrate (equiv.)
SO2Cl2 (equiv.)
Solventa
Time
Yield (%)b
1
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
3.0
3.0
3.0
6.0
6.0
6.0
12.0
12.0
6.0
6.0
6.0
6.0
DCM
DCM
DCM
DCM
DCM
DCM
–
15 min
1 h
<20
<30
40
2
3
12 h
4
15 min
6 h
20
5
45
6
12 h
50
7
15 min
30 min
12 h
60
8
-
80
9
DCE
THF
DMF
Acetone
40
10
11
12
12 h
Trace
Trace
Trace
12 h
Therefore, the scaffold 3 was chlorinated by utilizing sulfuryl chlo-
ride (SO2Cl2) at room temperature for 30 min, that furnished 1,3-
dichloro-2-(chloromethyl)-4,5,6-tris(propargyloxy)benzene 4 (Scheme
1) having two chlorine group at the position-1 and 3. Further, the
12 h
a
b
Anhydrous solvents were used.
Yields were reported after flash column chromatography (SiO2).
2

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
Scheme 2. Synthesis of cyclen-based dodecavalent-alkyne functionalized hypercore and single crystal XRD of the developed hypercore.
6-tetra-O-acetyl-β-D-galactopyranosyl azide 10 [30], and 2′,3′,6′,2′′,3′′,
4′′,6′′-hepta-O-acetyl-β-D-lactopyranosyl azide 11 [57] were synthesized
by the corresponding acetylated sugar derivatives using HBr (33%) in
acetic acid followed by azidation in DMF (Scheme 3). After chromato-
graphic purification, the developed azido derivatives were well char-
acterized by 1H and 13C NMR in the available experimental literature.
To this end, clickable 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl
azide 8, 2,3,4,6-tetra-O-acetyl- β-D-mannopyranosyl azide 9, 2,3,4,6-
tetra-O-acetyl-β-D-galactopyranosyl azide 10, and 2′,3′,6′,2′′,3′′,4′′,6′′-
hepta-O-acetyl-β-D-lactopyranosyl azide 11 were chosen as surface
group functionality and these were grafted over the dodeca-
propargylated scaffold i.e. hypercore 6 using the modular click
reaction to afford the (G0) glycodendrimers in good yields. After chro-
matographic refining, compounds 12–15 were isolated in 90%, 70%,
85% and 68% yields, respectively (Scheme 4). The symmetrically
dodeca-substituted cyclen cored glycodendrimers were fully elucidated
by 1H NMR, 13C NMR, IR and MALDI-TOF MS. The two distinct signals in
1H NMR at δ 8.67 and 8.37 ppm for compound 12, were observed with
ratio 2:1, which displayed the two chemically non-equivalent triazolyl
galactoside. In 13C NMR, the peak appeared at δ 143.7, 139.2 & 124.2,
123.4 ppm for compound 12, confirmed the presence of triazolyl car-
bons. In this continuation, the same NMR pattern was observed for tri-
azolyl region of synthesized glycodendrimers 13, 14 and 15. In addition,
complete absence of the characteristic alkyne peak in IR spectra
confirmed the unequivocal formation of desired final glycodendrimers.
The first generation galacto-dendron was developed by stitching AB3
monomer 4 with 2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl azide 10
using CuSO4 and sodium L-ascorbate to afford the chlorine functional-
ized dendritic wedge 16. The two distinct triazolyl peak at δ 8.24 and
8.10 ppm in 1H NMR for compound 16 were noticed with ratio 2:1,
which have shown the two chemically non-equivalent triazolyl galac-
tosides. While in 13C NMR, the peaks appeared at δ 143.7, 143.3 &
123.2, 122.7 ppm for compound 16, inferred the presence of triazolyl
carbons. Further, the chlorine functionalized dendritic architecture was
treated with NaN3 in DMF to afford the targeted azide functionalized
dendritic wedge 17 (Scheme 5). This transformation was elucidated by
IR and NMR spectra, in which, peak at 2104.5 confirms the formation of
Scheme 3. Synthesis of various azido-sugars (8–11).
3

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
Scheme 4. Synthesis of click inspired (G0) generation Glc-, Man-, Gal-, and Lac-, coated cyclen cored glycodendrimers.[a] Molar ratios: CuSO4/5H2O (0.3 equiv./
propargyl group), NaAsc (0.3 equiv./propargyl group), THF/Water (1:1, v/v), 45 ◦C; [b]Yields reported after purification by flash column chromatography (SiO2).
corresponding dendritic azide 17, while in 13C NMR down field shift was
noticed, during conversion from –CH2Cl (δ 41.2 ppm) to –CH2N3 (δ 49.3
ppm) for the scaffold 17, which substantiated the unequivocal formation
of respective azide dendron 17. Finally, the synthesized galactose coated
dendritic wedge was confirmed by its HRMS data.
corroborate the absence of free azide or alkyne functionality in the
constructed glycodendrimers, thereby supporting the generation of
targeted glycodendrimer 18 (See, Supporting Information, Figs. S37,
S38).
Moreover, the size exclusion chromatogram (SEC) displayed the size
progression from 12 adorned sugar glycodendrimer to 36-galactose
coated glycodendrimers, while the low polydispersity index (PDI)
ranging between 1.01 and 1.07 depicted the well defined molecular
structures of all the five synthesized glycodendrimers 12–15 and 18
(Fig. 2). In addition, retention time was also investigated and found to be
At the end, the azide-functionalized dendritic wedge 17 was grafted
over the hypercore 6 using CuSO4.5H2O/NaAsc under THF/Water (1:1)
to furnish the 36-galactose coated glycodendrimer 18 in quantitative
yield (Fig. 1). There was no vibrating band of azide and alkyne in IR
spectra of synthesized cyclen cored glycodendrimer 18 which
4

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
Scheme 5. Synthesis of click mediated azide functionalized galacto-conjugated first generation dendritic wedge (17).
Fig. 1. Structure of developed 36 peripheral galactose coated cyclen cored glycodendrimer (18).
15.28, 15.24, 15.24, 14.85 and 14.40 for glycodendrimers 12–15 and
18, respectively.
spectroscopy.
Absorption studies of developed cyclen-cored glycodendrimers were
also investigated, glycodendrimer 12, 13, 14, 15, 18 and hypercore 6
have shown UV–visible absorbance at 276.86, 276.39, 275.91, 275.44,
278.11 and 280.16 nm respectively (Fig. 3). By observing the absorption
pattern of developed glycodendrimers, it can be inferred that, the con-
structed dendrimers are synthesized from the same dendrimer core unit
6. Thus, we may come to a fruitful end where, core 6 is involved to build
these glyco-motifs, which was also substantiated by UV–Vis
3. Experimental
3.1. Materials & techniques
All reagents and solvents were of pure analytical grade. Thin layer
Chromatography (TLC) was performed on 60 F-254 silica gel, percoated
on aluminum plates and seen by UV lamp, 5% H2SO4/methanol solution
(charring agent). In addition, alkaline KMnO4 solution was used to
5

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
and extracted with ethyl acetate. The organic layer was washed with
saturated aq. NH4Cl (2 × 10 mL), water (10 mL) and finally with aq.
brine solution (2 × 5 mL). Organic layers were collected, dried over
anhydrous sodium sulphate, filtered, and evaporated under reduced
pressure (below 50 ◦C). The resulting crude mass was purified by flash
column chromatography to afford the targeted glyco-conjugate in good
yield.
3.3. Synthesis of methyl 3, 4, 5-tris(hydroxyl) benzoate (1)
To a stirred solution of 3,4,5-tris(hydroxyl)benzoic acid (5.0 g, 32.4
mmol) in anhydrous methanol (80 mL), the catalytic amount of conc.
H2SO4 (1.0 mL) was added dropwise in the cold condition. Then, the
reaction was refluxed for 4 h with constant stirring, after completion of
reaction (monitored by TLC), the resulting mixture was evaporated
under reduced pressure. The resulted crude mass was extracted with
ethyl-acetate, washed with aqueous NaHCO3 solution (2 × 50 mL), dried
over anhydrous Na2SO4, filtered and evaporated under reduced pressure
to afford targeted scaffold 1. The spectroscopic datas were matched
those reported in the literature [18].
Fig. 2. SEC diagram of the developed glycodendrimers 12–15 and 18.
3.4. Synthetic procedure for the synthesis of methyl 3, 4, 5-tris
(propargyloxy)benzoate (2)
To a solution of compound 1 (5.0 g, 27.1 mmol) in anhydrous
acetone, K2CO3 (26.30 g, 190 mmol, 8 equiv.) and 18-crown-6-ether
(250 μL) as co-catalyst were added, followed by the addition of prop-
argyl bromide (16.46 mL, 217 mmol, 8.0 equiv.). Then, the reaction was
refluxed for 12 h, upon completion of reaction (monitored by TLC),
resulting reaction mixture was evaporated under reduced pressure
(below 50 ◦C) to obtain the crude mass. The crude residue thus obtained
was subjected to flash column chromatography (SiO2) to afford the
desired compound 2 in 74% yield as white powder. The spectral datas
were matched with the reported literature [18].
Yield (6.0 g, 74%); Rf = 0.5 (15% Ethyl acetate/n-hexane); 1H NMR
(500 MHz, CDCl3): δ 7.45 (s, 2H), 4.81–4.79 (m, 6H), 3.90–3.89 (m, 3H),
2.53–2.52 (m, 2H), 2.45–2.44 (m, 1H); 13C NMR (125 MHz, CDCl3): δ
166.2, 151.2, 141.0, 125.7, 109.8, 78.6, 77.9, 76.1, 75.5, 60.2, 57.0, and
52.3 ppm.
Fig. 3. Absorbance spectra of the developed hypercore 6 and glycodendrimers
12–15 & 18.
3.5. Synthesis of 3, 4, 5-tris (propargyloxy)phenyl methanol (3)
locate the alkynes with subsequent heating. Flash column chromatog-
raphy was performed using silica gel (100–200) mesh size. The 1H and
13C spectra were recorded in 500 MHz and 125 MHz, respectively. All
NMR spectra were recorded at 25 ◦C and reported in ppm (δ) indicated
with respect to deuterated solvents. The resonance multiplicity in the 1H
NMR spectra are described as ‘s’ (singlet), ‘d’ (doublet), ‘dd’ (double
doublet), ‘t’ (triplet), and ‘m’ (multiplet) and residual protic solvent of
CDCl3 (1H NMR, 7.26 ppm; 13C NMR, 77.0 ppm). Mass spectra (MS) was
recorded on Sciex-X500R QTOF whereas MALDI-TOF MS (with 2,5-
To a solution of methyl 3,4,5-tris (propargyloxy)benzoate 2 (3.0 g,
10.05 mmol) in anhydrous THF (40.0 mL), LiAlH4 (0.45 g, 11.8 mmol,
1.2 equiv.) was added portion wise at 0 ◦C under inert condition (argon).
Then, the reaction was stirred for 6 h at room temperature till to the
completion of reaction (monitored by TLC). The resulting mixture was
quenched by 5% aq. NaOH and the resulting precipitate was filtered
through sintered funnel; next, the obtained filtrate was extracted with
ethyl acetate (150 mL), washed with water (2 × 20.0 mL) and subse-
quent brine wash. The extracted part was evaporated under reduced
pressure (below 50 ◦C), and the crude mass thus obtained was subjected
to flash column chromatography (SiO2) to produce the target compound
3 in 84% yield. The spectral data were closely matched with the reported
literature [54].
dihydroxy benzoic acid ‘DHB’,
α-cyano-4-hydroxycinnamic acid ‘4-
HCCA’ matrix). IR was recorded in Nujol mulls in KBr pellets. The
polydispersity index (Mw/Mn) of the developed samples was taken in
◦
DMF at 40 C with a flow rate of 0.5 mL/min on two polystyrene gel
columns. The calibration of columns were done against seven poly
(methyl methacrylate) (PMMA) standard samples. The absorbance
spectrum was also recorded by utilizing UV–Vis spectroscopy.
Yield (2.27 g, 84%); Rf = 0.5 (25% EtOAc/n-hexane); 1H NMR (500
MHz, CDCl3): δ 6.72 (s, 2H), 4.71–4.70 (m, 4H), 4.684–4.681 (m, 2H),
4.58 (s, 2H), 2.49–2.48 (m, 2H), 2.43 (t, J = 2.5 Hz, 1H); 13C NMR (125
MHz, CDCl3): δ 151.5, 137.2, 136.1, 106.8, 79.1, 78.4, 75.8, 75.1, 64.9,
60.2, and 56.8 ppm.
3.2. General experimental procedure for Cu(I)-catalyzed azide-alkyne
cycloaddition reaction
Polypropargylated alkyne analogues and its clickable counterparts i.
e. organic azides, CuSO.45H2O (0.3 equiv. per propargyl) and sodium
ascorbate (0.3 equiv. per propargyl) were heated in a mixture of THF/
Water (1:1) at 55 ◦C for 12 h. After the completion of reaction (moni-
tored by TLC), the resulting reaction mixture was passed through cellite,
3.6. Synthesis of dendritic wedge 1,3-dichloro-2-(chloromethyl)-4,5,6-
tris(propargyloxy)benzene (4)
A mixture of 3,4,5-tris (propargyloxy)phenyl methanol 3 (2.0 g, 7.39
mmol) and sulfuryl chloride (7.17 mL, 12.0 equiv.) were stirred for 30
6

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Carbohydrate Research 508 (2021) 108403
min at room temperature. Upon completion of reaction (monitored by
TLC), the resulting mixture was diluted with water followed by
neutralization using aq. NaOH (at 0 ◦C), then extracted with ethyl ace-
tate, dried over anhydrous Na2SO4, filtered, and evaporated under
reduced pressure (below 50 ◦C). Further, the resulting residue was pu-
rified by flash column chromatography to afford the compound 4 in
literature [18].
White crystalline solid, yield (3.25 g, 68%); Rf = 0.5 (40% ethyl
1
acetate/n-hexane); H NMR (500 MHz, CDCl3): δ 5.21 (t, J = 9.5 Hz,
1H), 5.10 (t, J = 9.5 Hz, 1H), 4.97–4.93 (m, 1H), 4.64 (d, J = 9.5 Hz,
1H), 4.28–4.25 (m, 1H), 4.18–4.15 (m, 1H), 3.80–3.77 (m, 1H),
2.09–2.07 (m, 6H), 2.02–2.0 (m, 6H); 13C NMR (125 MHz, CDCl3): δ
170.5, 170.0, 169.2, 169.1, 87.8, 73.9, 72.5, 70.6, 67.8, 61.6, 20.6, and
20.5 ppm.
1
good yield. Yield (2.11 g, 80%); Rf = 0.5 (15% EtOAc/n-hexane); H
NMR (500 MHz, CDCl3): δ 4.81 (s, 4H), 4.76 (s, 4H), 2.51 (s, 1H), 2.49 (s,
2H); 13C NMR (125 MHz, CDCl3): δ 146.9, 146.3, 129.9, 126.3, 77.86,
77.83, 76.6, 76.4, 61.2, 61.0, and 41.1 ppm; HRMS: m/z = C16H12Cl3O+3 ;
calculated = 356.9847; found = 356.9874 (M + H)+.
3.10. Synthesis of 2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl azide (9)
This compound was synthesized as the procedure of compound 8
[18], and the NMR data was matched with the earlier reported literature
[60]. Yellow viscous, yield (1.91 g, 40%); Rf = 0.4 (40% ethyl aceta-
te/n-hexane); 1H NMR (500 MHz, CDCl3): δ 5.42 (s, 1H), 5.25–5.21 (m,
1H), 5.03–5.0 (m, 1H), 4.72 (s, 1H), 4.26–4.23 (m, 1H), 4.19–4.16 (m,
1H),3.76–3.73 (m, 1H), 2.18 (s, 3H), 2.08 (s, 3H), 2.02 (s, 3H), 1.96 (s,
3H); 13C NMR (125 MHz, CDCl3): δ 170.5, 169.87, 169.85, 169.4, 85.0,
74.5, 70.8, 69.1, 65.2, 62.2, 20.6, 20.5 and 20.4 ppm.
3.7. Synthesis of novel hypercore (6)
The azamacrocycle cyclen unit 5 (20 mg, 0.116 mmol, 1.0 equiv.)
and 1,3-dichloro-2-(chloromethyl)-4,5,6-tris(propargyloxy)benzene
4
(187 mg, 0.522 mmol, 4.5 equiv.) were dissolved in a mixture of
aqueous NaOH (1 M, 15 mL) and CH3CN (15 mL). The reaction was
allowed to stir for 10 h at room temperature, and the resulting mixture
was extracted with ethyl acetate (2 × 75 mL). The organic layer was
collected, dried over anhydrous Na2SO4, filtered and then evaporated
3.11. 2,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl azide (10)
◦
under reduced pressure (below 50 C). The obtained crude mass was
subjected to column chromatography (SiO2) to afford the desired
hypercore 6 in good yield (70%). Yield (118 mg, 70%); Rf = 0.3 (25%
EtOAc/n-hexane); 1H NMR (500 MHz, CDCl3): δ 4.81 (d, J = 2.0 Hz, 8H),
4.76–4.75 (m, 16H), 3.61 (s, 8H), 2.75 (s, 16H), 2.50 (t, J = 3.0 Hz,
12H); 13C NMR (125 MHz, CDCl3): δ 146.3, 144.8, 131.94, 126.96, 78.1,
78.0, 76.3, 76.2, 60.9, 60.7, 54.7, and 50.5 ppm. IR (KBr): νmax 3289.27,
3259.16, 2931.97, 2125.90, 1570.69, 1450.89 cm1. HRMS: m/z =
The glycosylated azide 10 was synthesized as the procedure of earlier
reported literature, and the NMR data were also matched [30]. White
1
solid, yield (3.53 g, 74%); Rf = 0.5 (45% ethyl acetate/n-hexane); H
NMR (500 MHz, CDCl3): δ 5.41 (d, J = 2.5 Hz, 1H), 5.15 (t, J = 9.5 Hz,
1H), 5.04–5.01 (m, 1H), 4.59 (d, J = 9.0 Hz, 1H), 4.19–4.12 (m, 2H),
4.01 (t, J = 6.5 Hz, 1H), 2.16 (s, 3H), 2.08 (s, 3H), 1.98 (s, 3H), 13C NMR
(125 MHz, CDCl3): δ 170.3, 170.0, 169.9, 169.3, 88.2, 72.8, 70.6, 68.0,
66.8, 61.1, 20.6, 20.5, and 20.4 ppm.
C
72H61Cl8N4O+12; calculated = 1457.1730; found = 1457.1626 (M +
H)+.
3.12. 2′,3′,6′,2′′,3′′,4′′,6′′-hepta-O-acetyl-β-D-lactopyranosyl azide (11)
3.8. General procedure for the acetylation of sugar scaffolds (A)
To a stirred solution of per-o-acetylated D-lactose (5.0 g, 7.55 mmol)
in anhydrous DCM at 0 ◦C, HBr (33%) in acetic acid (12 mL) was added
and the resulting reaction mixture was stirred for 6 h at (0- to 10 ◦C).
Upon completion of the reaction (monitored by TLC), the resulting
mixture was diluted with DCM, and then washed with sodium bicar-
bonate solution. The organic layer was collected and dried over anhy-
drous Na2SO4, filtered, and evaporated in vacuo to obtain per-O-
acetylated lactose bromide. Further, anomeric bromide (4.2 g, 6.0
mmol) and NaN3 (1.17 g, 18.0 mmol) were dissolved in anhydrous DMF,
The procedure was carried out according to the earlier reported
literature [59]. D-sugars i.e. Glu, Man, Gal and Lac (5.0 g each) were
taken in a round bottom flask, already having acetic anhydride (25 mL
for Glc, Gal, and Man, while 50 mL for Lac) followed by addition of
iodine (0.25 g for Glc, Gal and Man, while 0.5 g for Lac) and then the
reaction was stirred for 8 h. After the completion of reaction, DCM was
added to dilute the reaction media, and then washed with hypo solution
followed by sodium carbonate solution. Organic layer was collected,
dried over anhydrous Na2SO4, filtered and evaporated (below 50 ◦C) to
obtain the targeted acetylated sugars in good yields. The synthesized
compounds were well characterized by the NMR in the available
experimental literature [59].
◦
and the reaction was stirred at 80 C for 6 h. After the completion of
reaction (monitored by TLC), solvent was evaporated under reduced
pressure (below 50 ◦C), extracted with EtOAc (2 × 100 mL) and finally
washed with cold water (2 × 15 mL). The organic layer was evaporated
under vacuum (below 50 ◦C), and the resulted crude mass was purified
using flash column chromatography (SiO2) to afford high yield of lactose
azide 11 (72%). Further, the spectral data was matched with the earlier
reported literature [61].
3.9. Synthesis of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide (8)
The procedure was carried out according to the earlier reported
literature [18]. To a stirred solution of per-o-acetylated D-glucose 7 (5.0
g, 12.8 mmol) in anhydrous DCM at 0 ◦C, HBr (33%) in acetic acid (12
mL) was added slowly and the resulting mixture was stirred for 3–4 h at
(0–10 ◦C). Upon completion of the reaction (monitored by TLC), the
reaction mixture was diluted with DCM, and then washed with sodium
bicarbonate solution. The organic layer was collected and dried over
anhydrous Na2SO4, filtered, and evaporated in vacuo to obtain per--
O-acetylated galactose bromide. Further, anomeric bromide (4.0 g, 9.7
mmol) and NaN3 (1.89 g, 29.2 mmol) were dissolved in anhydrous DMF,
Yellow liquid, yield (3.51 g, 72%); Rf = 0.4 (60% ethyl acetate/n-
hexane); 1H NMR (500 MHz, CDCl3): δ 5.33 (s, 1H), 5.19 (t, J = 9.0 Hz,
1H), 5.10–5.06 (m, 1H), 4.94 (d, J = 10.5 Hz, 1H), 4.84 (t, J = 9.0 Hz,
1H), 4.61 (d, J = 8.5 Hz, 1H), 4.50–4.46 (m, 2H), 4.11–4.06 (m, 3H),
3.87–3.78 (m, 2H), 3.70–3.69 (m, 1H), 2.12 (d, J = 7.0 Hz, 6H),
2.05–2.03 (m, 12H), 1.94 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 170.29,
170.27, 170.06, 170.0, 169.5, 169.4, 16.0, 101.0, 87.6, 75.7, 74.7, 72.4,
70.9, 70.8, 70.7, 69.0, 66.5, 61.6, 60.7, 20.7, 20.6, 20.5, and 20.4 ppm.
◦
and the reaction was stirred at 80 C for 6 h. After the completion of
3.13. Synthesis of glucose coated cyclen cored ‘G0’ glycodendrimer 12
reaction (monitored by TLC), solvent was evaporated, extracted with
EtOAc and finally washed with cold water two times. The organic layer
was evaporated under vacuum (below 50 ◦C) to obtain the crude mass,
thus the obtained residue was subjected to column chromatography
(SiO2) to afford the 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl azide 8 in
good yield. The NMR data was also matched with earlier reported
Compound 8 (153 mg, 411
μ
mmol, 15.0 equiv.) was reacted with
mol, 4.5
mol, 4.5 equiv) in THF/
hypercore 6 (40 mg, 27.4 mol), CuSO4⋅5H2O (31 mg, 123
μ
μ
equiv), and sodium L-ascorbate (24 mg, 123
μ
water (1:1) using procedure A. The resulting residue was purified by
silica gel column chromatography (DCM/MeOH) to afford
7

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
glycodendrimer 12 as a white solid; Yield (146 mg, 90%), Rf = 0.5 (5%
MeOH/CH2Cl2); 1H NMR (500 MHz, CDCl3): δ 8.67 (s, 4H), 8.37 (s, 8H),
6.10 (d, J = 9.5 Hz, 12H), 5.74–5.63 (m, 12H), 5.44–5.31 (m, 44H),
4.98–4.89 (m, 4H), 4.26–4.10 (m, 36H), 3.45 (s, 8H), 2.59 (s, 16H), 2.07
MeOH/CH2Cl2); 1H NMR (500 MHz, CDCl3): δ 8.51 (s, 4H), 8.26 (s, 8H),
5.99–5.93 (m, 12H), 5.65–5.59 (m, 12H), 5.46–5.43 (m, 12H), 5.36 (s,
12H), 5.19–5.10 (m, 36H), 5.02–5.00 (m, 12H), 4.65 (dd, J = 19.5, 7.5
Hz, 12H), 4.51 (d, J = 11.0 Hz, 12H), 4.22–3.98 (m, 72H), 3.63 (s, 8H),
2.78 (s, 16H), 2.15 (s, 36H), 2.05–2.01 (m, 144H), 1.96 (s, 36H),
1.80–1.78 (m, 36H); 13C NMR (125 MHz, CDCl3): δ 170.4, 170.3, 170.1,
170.0, 169.7, 169.2, 147.6, 143.75, 143.72, 143.6, 139.4, 127.04,
127.01,124.3, 124.2, 124.1, 123.4, 115.9, 114.1, 101.0, 85.1, 75.6,
72.9, 70.9, 70.55, 70.51, 69.1, 66.6, 62.1, 60.6, 20.7, 20.6, 20.4, and
20.2 ppm; IR (KBr): νmax3453.88, 2924.61, 2853.37, 1754.95, 1371.68,
1229.91 cmꢀ 1. MALDI-TOF MS: Exact mass: C384H480Cl8N40O216
calculated = 9386.5314; found = 9383.315.
(s, 36H), 2.03 (s, 36H), 1.96 (s, 12H), 1.89 (s, 24H), 1.78 (s, 36H); 13
C
NMR (125 MHz, CDCl3): δ 170.59, 170.5, 170.1, 16.6, 169.5, 168.9,
168.6, 146.7, 145.3, 143.7, 139.2, 126.9, 124.2, 123.4, 118.9, 113.9,
85.4, 74.8, 74.6, 73.0, 70.2, 70.0, 67.8, 67.6, 65.4, 61.6, 61.4, 20.6,
20.5, 20.4, 20.1, and 20.0 ppm.IR (KBr): νmax3422.28, 2956.59,
2923.79, 2852.60, 1754.96, 1463.73, 1226.67 cmꢀ 1. MALDI-TOF MS:
Exact mass: C240H288Cl8N40O120Na + calculated = 5958.5072; found =
5957.218 (M + Na)+.
3.14. Synthesis of G(0) generation mannose coated cyclen cored
glycodendrimer 13
3.17. Synthesis of glycoconjugate dendron 16
The scaffold 1,3-dichloro-2-(chloromethyl)-4,5,6-tris(propargyloxy)
benzene 4 (0.1 g, 0.279 mmol) was reacted with 2,3,4,6-tetra-O-acetyl-
β-D-galactopyranosyl azide 10 (417 mg, 1.11 mmol, 4.0 equiv.), using
CuSO4⋅5H2O (62 mg, 0.251 mmol, 0.9 equiv.), and sodium L-ascorbate
(50 mg, 0.251 mmol, 0.9 equiv.) under THF/water (1:1) solvent ac-
cording to procedure A. The resulting crude was purified by flash col-
umn chromatography (SiO2) to furnish the chlorine functionalized
glycoconjugate 16 in good yield. Yield (330 mg, 80%) Rf = 0.4 (60%
ethyl acetate/n-hexane); 1H NMR (500 MHz, CDCl3): δ 8.24 (s, 1H), 8.10
(s, 2H), 5.89 (d, J = 9.5 Hz, 3H), 5.64–5.60 (m, 3H), 5.54 (s, 3H),
5.31–5.24 (m, 9H), 4.83 (s, 2H), 4.26–4.11 (m, 9H), 2.22–2.21 (m, 9H),
2.03–1.99 (m, 18H), 1.84–1.81 (m, 9H); 13C NMR (125 MHz, CDCl3): δ
170.3, 170.09, 170.03, 169.8, 168.9, 147.7, 146.9, 143.7, 143.6, 129.8,
126.0, 123.2, 122.7, 86.1, 73.84, 73.80, 70.8, 67.8, 67.7, 66.8, 66.4,
66.3, 61.0, 60.3, 41.2, 20.6, 20.5, 20.4, 20.19, and 20.14 ppm; HRMS:
m/z = C58H68Cl3N9O30K+; calculated = 1516.2740; found = 1516.2721
(M + K)+.
2,3,4,6-tetra-O-acetyl-β-D-mannopyranosyl azide 9 (153 mg, 411
μ
mmol, 15.0 equiv) was reacted with hypercore 6 (40 mg, 27.4 μmol), in
the presence of catalyst CuSO4⋅5H2O (31 mg, 123
μmol, 4.5 equiv), and
sodium L-ascorbate (24 mg, 123 mol, 4.5 equiv) in THF/water (1:1)
μ
using procedure A. The resulting residue was purified by flash column
chromatography (SiO2) using a gradient of DCM/MeOH to afford gly-
codendrimer 13 as a white solid. Yield (114 mg, 70%) Rf = 0.4 (5%
MeOH/CH2Cl2); 1H NMR (500 MHz, CDCl3): δ 8.46 (s, 4H), 8.29 (s, 8H),
6.32 (s, 12H), 5.76 (s, 12H), 5.42–5.39 (m, 24H), 5.19–5.09 (m, 24H),
4.33–4.22 (m, 24H), 4.07 (s, 12H), 3.65 (s, 8H), 2.81 (s, 16H), 2.09 (s,
36H), 2.05 (s, 36H), 2.01 (s, 24H), 1.98 (s, 48H); 13C NMR (125 MHz,
CDCl3): δ 170.8, 170.7, 169.9, 169.8, 169.7, 169.5, 147.5, 143.1, 132.1,
127.0, 124.2, 123.9, 114.0, 84.4, 75.3, 70.8, 68.6, 66.5, 66.2, 65.4, 65.3,
62.6, 62.4, 54.8, 50.0, 20.7, 20.6, 20.5, and 20.4 ppm; IR (KBr):
νmax3472.94, 2924.87, 2853.30, 1755.15, 1371.33, 1225.41 cmꢀ 1
.
MALDI-TOF MS: Exact mass:
C240H288Cl8N40O120 calculated =
5935.5180; found = 5934.975.
3.18. Synthesis of glycoconjugate dendron 17
3.15. Synthesis of G(0) generation galactose coated cyclen cored
glycodendrimer 14
To a solution of glycoconjugate dendron 16 (0.3 g, 0.203 mmol) in
DMF, sodium azide (52 mg, 0.812 mmol, 4.0 equiv.) was added under
inert condition and the reaction was stirred at 80 ◦C for 14 h. The
resulting reaction mixture was evaporated in vacuo, and the residue was
extracted with EtOAc (2 × 20 mL), washed with brine solution (2 × 15
mL) and dried over anhydrous Na2SO4. The organic layer was concen-
trated and subjected to column chromatography to afford the desired
azide functionalized dendritic wedge 17 in excellent yield. Yield (295
mg, 98%); Rf = 0.4 (60% ethyl acetate/n-hexane); 1H NMR (500 MHz,
CDCl3): δ 8.17 (s, 1H), 8.06 (s, 2H), 5.86 (d, J = 9.0 Hz, 3H), 5.57–5.48
(m, 6H), 5.26–5.19 (m, 9H), 4.57 (s, 2H), 4.42–4.03 (m, 9H), 2.16–2.15
(m, 9H), 1.96–1.93 (m, 18H), 1.78–1.75 (m, 9H); 13C NMR (125 MHz,
CDCl3): δ 170.1, 169.97, 169.91, 169.6, 168.7, 147.5, 146.6, 143.5,
143.3, 127.8, 126.0, 123.1, 122.6, 85.8, 73.6, 70.6, 67.6, 66.7, 66.1,
60.9, 60.1, 49.3, 20.8, 20.4, 20.2, and 19.9 ppm; IR (KBr): νmax 3452.12,
2925.42, 2853.98, 2105.01, 1754.93, 1371.87, 1220.37 cmꢀ 1; HRMS:
m/z = C58H69Cl2N12O+30; calculated = 1483.3615; found = 1483.3653
(M + H)+.
2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl azide 10 (153 mg, 411
mmol, 15.0 equiv.) was reacted with hypercore 6 (40 mg, 27.4 mol),
in the presence of catalyst CuSO4⋅5H2O (31 mg, 123 mol, 4.5 equiv.),
and sodium L-ascorbate (24 mg, 123 mol, 4.5 equiv.) in THF/water
μ
μ
μ
μ
(1:1) using method described in general experimental procedure. The
resulting residue was purified by flash column chromatography (SiO2)
using a gradient of DCM/MeOH to afford glycodendrimer 14 as a white
solid; Yield (138 mg, 85%); Rf = 0.5 (40% MeOH/CH2Cl2); 1H NMR
(500 MHz, CDCl3): δ 8.44 (s, 4H), 8.25 (s, 8H), 5.98–5.93 (m, 12H),
5.72–5.67 (m, 12H), 5.54 (s, 12H), 5.31–5.19 (m, 36H), 4.33–4.16 (m,
36H), 3.67 (s, 8H), 2.83 (s, 16H), 2.23–2.20 (m, 36H), 2.0 (d, J = 12.5
Hz, 72H), 1.78–1.77 (m, 36H); 13C NMR (125 MHz, CDCl3): δ 170.3,
170.2, 170.1, 169.8, 168.8, 147.4, 145.8, 143.7, 131.9, 126.9, 124.0,
123.6, 85.9, 85.8, 73.6, 70.9, 67.9, 67.7, 66.8, 66.4, 66.2, 61.0, 60.9,
54.8, 50.2, 20.5, 20.4, 20.16, and 20.12 ppm; IR (KBr): νmax 3473.14,
2924.59, 2853.37, 1755.15, 1371.91, 1222.14 cmꢀ 1; MALDI-TOF MS:
Exact mass: C240H288Cl8N40O120 calculated = 5935.5180; found =
5796.566.
3.19. Synthetic procedure for 36 peripheral galactosylated
glycodendrimer (18)
3.16. Synthesis of G(0) generation lactose coated cyclen cored
glycodendrimer 15
The glycoconjugate dendron 17 (229 mg, 154 μmol, 15.0 equiv.) was
reacted with hypercore unit 6 (20 mg, 10.2
μ
mol), CuSO.45H2O (15 mg,
2′,3′,6′,2′′,3′′,4′′,6′′-hepta-O-acetyl-β-D-lactopyranosyl azide 11 (204
61.7 μmol, 6.0 equiv.), and sodium-L-ascorbate (12 mg, 61.7 μmol, 6.0
mg, 309
μ
mmol, 15.0 equiv) was reacted with hypercore 6 (30 mg, 20.6
equiv) according to procedure A to afford the glycodendrimer 18 in
moderate yield. Yield (99 mg, 50%); Rf = 0.50 (10% MeOH/CH2Cl2); 1H
NMR (500 MHz, CDCl3): δ 8.39–8.33 (m, 12H), 8.22–8.16 (m, 28H),
8.08 (s, 8H), 5.97–5.94 (m, 36H), 5.81–5.77 (m, 27H), 5.66–5.64 (m,
36H), 5.54 (d, J = 7.5 Hz, 36H), 5.29–5.23 (m, 127H), 5.00–4.90 (m,
8H), 4.33–4.14 (m, 108H), 3.72 (s, 8H), 2.86 (s, 16H), 2.22–2.18 (m,
μ
mol), in the presence of CuSO4⋅5H2O (23 mg, 92.6
μ
mol, 4.5 equiv.),
and sodium L-ascorbate (18 mg, 92.6
μmol, 4.5 equiv.) in THF/water
(1:1) using procedure A. The resulting residue was purified by flash
column chromatography (SiO2) using a gradient of DCM/MeOH afford
glycodendrimer 15 as a white solid; Yield (131 mg, 68%) Rf = 0.3 (5%
8

A.K. Agrahari et al.
Carbohydrate Research 508 (2021) 108403
108H), 2.02–1.96 (m, 216H), 1.83–1.76 (m, 108H); 13C NMR (125 MHz,
CDCl3): δ 170.3, 170.18, 170.13, 169.8, 168.8147.9, 147.8, 147.5,
145.4, 143.54, 143.52, 143.4, 126.9, 126.8, 124.3, 124.0, 123.6, 123.3,
119.0, 115.2, 115.1, 114.0, 86.0, 85.9, 85.8, 73.6, 70.9, 67.9, 67.8, 66.9,
66.8, 66.33, 66.30, 61.0, 20.6, 20.5, and 20.1 ppm; IR (KBr): νmax
3463.87, 2923.19, 2852.27, 1755.06, 1371.92, 1222.54 cmꢀ 1. MALDI-
TOF MS: Exact mass: C768H876Cl32N148O372 calculated = 19240.4212;
found = 19300 (aprox).
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The work described herein constitutes the development of high
functional glycodendrimer at lowest possible generation by utilizing
double stage convergent method. On one hand, the use of a chlorine-
containing hypercore derived from cyclen scaffold; possessing 12
alkynyl functionalities facilitate the expeditious synthesis of G0 and G1
generation glycodendrimers in good yields by using the click chemistry.
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Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
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