Click inspired synthesis of triazole-linked vanillin glycoconjugates

Article abstract of DOI:10.1007/s10719-016-9729-4

The 1,3-dipolar cycloaddition of deoxy-azido sugars 1 with alkyne derivatives of p-vanillin, 3-methoxy-4-(prop-2-ynyloxy)benzaldehyde (2) and 2-methoxy-1-(prop-2-ynyloxy)-4-((prop-2-ynyloxy)methyl)benzene) (4) to afford regioselective triazole-linked vanillinglycoconjugates 5 and 6 was investigated in the presence of CuI/DIPEA in dichloromethane. All the developed glycoconjugates were characterized on the basis of IR, NMR, and MS. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10719-016-9729-4

Glycoconj J
DOI 10.1007/s10719-016-9729-4
ORIGINAL ARTICLE
Click inspired synthesis of triazole-linked vanillin glycoconjugates
Pratibha Dwivedi1,2 & Kunj B. Mishra1 & Pritika2 & Bhuwan B. Mishra1,2
&
Vinod K. Tiwari1
Received: 18 May 2016 /Revised: 19 August 2016 /Accepted: 2 September 2016
#
Springer Science+Business Media New York 2016
Abstract The 1,3-dipolar cycloaddition of deoxy-azido sugars
1 with alkyne derivatives of p-vanillin, 3-methoxy-4-(prop-2-
ynyloxy)benzaldehyde (2) and 2-methoxy-1-(prop-2-ynyloxy)-
4-((prop-2-ynyloxy)methyl)benzene) (4) to afford regioselec-
tive triazole-linked vanillinglycoconjugates 5 and 6 was inves-
tigated in the presence of CuI/DIPEA in dichloromethane. All
the developed glycoconjugates were characterized on the basis
of IR, NMR, and MS.
to exhibit unusual biological activities as the different molec-
ular segments act cooperatively [4–6].
Glutathione-S-transferase(s) (GST) enzyme from Brugia
malayi has been exploited as a target in lymphatic filariasis
therapeutics [7]. The components of the glutathione (GSH)
system, mainly GST enzymes, are critical, antioxidant and
detoxification compounds responsible for the long-term exis-
tence of filarial worms in the mammalian host. Inhibition of
parasitic GST affects the survival of the parasites or helps in
the enhancement of activity of presently available antifilarial
drugs. Hence, they are major chemotherapeutic targets in fi-
larial species. Azeez et al., docked 58 phytochemicals from
different plants to GST enzyme of B. malayi, and assessed
their binding affinity and consequently their inhibitory activ-
ity. Among these phytochemicals, the compound p-vanillin by
virtue of forming greater number of hydrogen bonds and
strong hydrogen bonding interactions to GST, was identified
as a promising lead to treat lymphatic filariasis [8]. However,
the limited solubility of p-vanillin in water restricts its perva-
sive application. Therefore, development of glycohybrids
consisting of sugar residues fastened to p-vanillin via triazole
moiety would be crucial as the resulting triazolyl
glycoconjugates with fare water solubility in addition to the
ability of triazole ring to contribute in numerous noncovalant
interactions, including hydrogen bonding dipole-dipole inter-
actions, and π-stacking interactions etc. may have added stim-
ulus in GST inhibitory activity.
.
.
.
Keywords Vanillin Click chemistry Carbohydrates
Glycoconjugates
Introduction
The coupling of two or more molecular entities with distinct
properties to form novel conjugates with combined properties
of parent components via ‘click’ chemistry, has emerged as a
fast growing technology in recent years [1–3]. Several new
conjugates arising through such conjugation have been found
Electronic supplementary material The online version of this article
(doi:10.1007/s10719-016-9729-4) contains supplementary material,
which is available to authorized users.
* Bhuwan B. Mishra
bbmchem@gmail.com; bhuwan@ciab.res.in
Among the reactions comprising the click universe, the
perfect example is the Huisgen 1,3-dipolar cycloaddition of
terminal alkynes and organic azides to form 1,4-disubstituted-
1,2,3-triazoles [9–11]. In addition, because of the important
role of carbohydrates in biological systems [12, 13], and their
great chemotherapeutic potential [14], a wide variety of
glycoconjugates so far have been reported using azide-
alkyne cycloaddition approach [15–20]. However, the
* Vinod K. Tiwari
tiwari_chem@yahoo.co.in
1
Department of Chemistry, Centre of Advanced Study, Faculty of
Science, Banaras Hindu University, Varanasi -221005, India
2
Center of Innovative and Applied Bioprocessing (CIAB), C-127,
IInd Floor, Phase VIII, Industrial Area, SAS Nagar,
Mohali, Punab -160071, India

Glycoconj J
synthesis of p-vanillin glycoconjugates via ‘click’ chemistry
has not yet realized. Thus, in view of strong binding efficacy
of p-vanillin to GST of B. malayi, and the utility of carbohy-
drates in numerous chemical, biological, medicinal, and phar-
macological investigations, we herein report the high-yielding
synthesis of triazole-linked vanillin glycoconjugates 5 and 6
via Cu(I) catalyzed click reaction of azido-sugars (1a-i) and p-
vanillin based terminal alkynes 2 and 4. We also investigated
the deprotection of representative compounds, i.e. 5a, 6c, 6f,
and 6i to afford glycoconjugates 7–10 bearing triazolyl
fastend sugar residues attached to vanillin skeleton. To the
best of our knowledge no such effort has been made earlier,
and all the developed terminal alkynes 2 and 4 in addition to
triazolyl glycoconjugates 5–10 are novel.
unaffected by most organic and inorganic functional groups
[15, 16]. Hence, the CuAAC reaction of terminal alkyne 2
(95 mg, 0.5 mmol) and azido-sugar 1a (1.2 eqv, 0.6 mmol)
was carried out in presence of DIPEA (0.087 ml, 0.5 mmol)
and CuI (47 mg, 0.25 mmol) in dry CH2Cl2 at room temper-
ature under inert atmosphere for 10 h to afford 1-(5-((4-for-
myl-2-methoxyphenoxy)methyl)-1H-1,2,3-triazol-1-yl)-
2,3,4-tri-O-acetyl-β-D-xylopyranose 5a regioselectively in
94 % yields. The regioisomeric nature of compound 5a was
established based on its spectroscopic data. In mass spectrum,
compound 5a displayed a molecular ion peak [M + H]+ at m/z
492. The 300 MHz 1H NMR spectrum of compound 5a exhib-
ited a total of twenty five proton resonances. A singlet integrat-
ed to one proton appeared at δ 9.83 was identified for aldehydic
function while a triazolyl proton singlet resonated at δ 7.92. A
multiplet integrated to two protons observed between δ 7.43–
7.32 in addition to a one proton doublet resonated at δ 7.16
(J = 8.7 Hz) was attributed for unsubstituted positions in phe-
nyl-ring. The anomeric proton of xylose resonated as doublet at
δ 5.84 (J = 8.4 Hz) while a multiplet integrated to four protons
was attributed to a oxymethylene function and two sugar pro-
tons. The proton resonances corresponding to three acetyl func-
tions in compound 5a were observed as singlets, three proton
each appeared at δ 2.07, δ 2.04, and δ 1.83. Finally, single-
crystal X-ray analysis unambiguously evidenced the structure
of compound 5a (Fig. 1 & Table 1).
Result and discussion
The synthetic strategy begins with the cheap and readily avail-
able monosaccharides, i.e., D-glucose, D-galactose and D-
xylose etc., which after processing to a number of high-
yielding steps for protection and modification, afforded
deoxy-azido sugars 1a-i in good yields [21–26].
After the synthesis of azido-sugars 1a-i, we next attempted the
synthesis of p-vanillin based terminal alkynes 2 & 4. The
propargylation of p-vanillin using Cs2CO3 in dry DMF under
inert condition furnished 3-methoxy-4-(prop-2-
ynyloxy)benzaldehyde 2 in excellent yields. Likewise, terminal
alkyne 2-methoxy-1-(prop-2-ynyloxy)-4-((prop-2-
ynyloxy)methyl)benzene) 4 was prepared by reduction of p-van-
illin with NaBH4 in dry THF at room temperature followed by
propargylation of resulting 4-(hydroxymethyl)-2-methoxyphenol
3 in presence of Cs2CO3 in dry DMF (Scheme 1).
Once having established the reaction conditions for the
regioselective cycloaddition of p-vanillin based alkyne 2 and
the azido-sugar 1a, we explored the scope of other sugar
azides in such a cycloaddition, and prepared a library of
triazole-linked vanillin glycoconjugates 5 in efficient yields
(Table 2). We also investigated the reaction under microwave
(MW) condition, where a significant reduction of reaction time
to 10 min was observed.
Once the synthesis of terminal alkynes 2 and 4 was accom-
plished, we further explored their click reaction with deoxy-
azido sugars 1(a-i). Generally, CuAAC reaction proceeds in
many protic and aprotic solvents, including water, and is
The structures of all the developed glycoconjugates 5 were
1
elucidated using spectral studies (IR, H, and 13C NMR).
Single-crystal X-ray analysis unambiguously evidenced the
structure of compound 5b (Fig. 2).
Further, we extended the work, and successfully prepared a
series of bis-triazolyl vanillin-glycoconjugates 6 by reaction
of alkyne 4 with azido-sugars 1 under optimized reaction con-
dition (Table 3). The structure of all the developed
glycoconjugates 6 were deduced from their spectral studies
(IR, NMR, and MS).
Fig. 1 Molecular structure of 5a. Thermal ellipsoids of C, N, and O are
Scheme 1 Synthesis of p-vanillin based terminal alkynes 2 and 4
set at 40 % probability

Glycoconj J
Table 1 Crystallographic refinement data for compound 5a
Table 2 Synthesis of triazole-linked p-vanillin glycoconjugates 5 via
CuAAC reaction
Property
Data
Empirical Formula
Formula Weight
Crystal System
Space group
a (Å)
C22 H25 N3 O10
491.45
Entrya
Sugar azides
Click productb
Yield (%)c
Yield (%)d
Monoclinic
P 21
1
94
95
12.8377(16)
5.4479(4)
1a
b (Å)
c (Å)
17.5773(15)
90, 105.297(11), 90
1185.8(2)
α, β, γ (o)
V (Å3)
5a
92
92
2
Z
2
Density (calc)
F(000)
1.376
1b
516
μ (mm−1
)
0.110
Crystal Size [mm]
Temperature (K)
Radiation / λ
0.16 x 0.18 x 0.24
293
5b
3
90
90
MoK\α / 0.71073
3.18, 29.10
-17:10; −6:6; −24:21
5128, 4193, 0.030
2183
θ Min-Max [o]
1c
h, k, l
Tot.,UniqData, R(int)
Obs. data [I > 2.0 σ(I)]
Nref, Npar
5c
4
92
94
5128, 156
R1, wR2, S
0.0642, 0.1672, 1.041
0.00, 0.00
1d
Max.and Av. Shift/Error
Min. - Max. resd. Dens. [e/ Å3]
CCDC
-0.241, 0.198
1,472,356
5d
5
90
92
Considering the wide application of sugar-containing
macrocycles in different fields [15], we extended the
synthesis, and successfully developed a macrocycle
comprising bis-triazolyl vanillin glycoconjugate 6i
(78 % isolated yield) by the reaction of alkyne 4 (1.0
equiv) with bis deoxy-azido sugar 1i (1.2 equiv) in
presence of CuI (0.5 equiv) and DIPEA (1.0 equiv) at
room temperature for 10 h under optimized reaction
conditions. Reaction time was significantly reduced to
10 min, when reaction was carried out under microwave
at 100 °C with a stirring rate 200 rpm (Scheme 2).
Finally, for a near future in vitro assay against B. malayi, we
need to remove the various carbohydrate protecting groups
from glycoconjugates (5 & 6), therefore, representative com-
pounds 5a, 6f, and 6i were treated with sodium methoxide in
anhydrous methanol for 24 h at room temperature to afford
corresponding glycoconjugates 7, 8, and 9, respectively
(Fig. 3). Likewise, isopropylidene protected glycoconjugate
6c was deprotected using trifluoroacetic acid-water (3:2 v/v)
in 2 h to afford corresponding triazolyl glycoconjugate 10.
The structure of deprotected glycoconjugates were deduced
from their spectral studies (IR, NMR, and MS).
1e
5e
6
94
93
1f
5f
7
92
92
1g
5g
a Molar ratios: deoxy-azido sugar 1 (1.2 equiv), vanillin alkyne 2 (1.0
equiv), CuI (0.5 equiv) and DIPEA (1.0 equiv)
b Vanillin triazolyl glycoconjugates
c Isolated yield at rt. (time 10 h)
d Isolated yield through reaction under microwave at 100 °C with a stir-
ring rate 200 rpm in 10 min

Glycoconj J
General procedure for synthesis
of 3-methoxy-4-(prop-2-ynyloxy) benzaldehyde (2)
To a solution of p-vanillin (5.0 g, 32.9 mmol) in DMF
(50 mL), caesium carbonate (1.2 equiv., 12.86 g, 39.48 mmol)
and propargyl bromide (1.3 equiv., 3.2 mL, 42.8 mmol) were
added under inert condition. The reaction mixture was stirred
for 12 h at room temperature. After completion of reaction
(monitored by TLC), the reaction mixture was in vacuo con-
centrated, extracted with CH2Cl2, and washed twice with
10 % Na2CO3, water, and brine solution. The organic layer
was dried over anhydrous Na2SO4. Residue obtained after
removal of solvent was purified by flash column chromatog-
raphy using gradient mixtures of n-hexane-ethyl acetate as
eluent to afford compound 2.
Fig. 2 Molecular structure of 5b. Thermal ellipsoids of C, N, and O are
set at 40 % probability (CCDC 1022190)
Conclusion
Diverse deoxy-azido sugars were prepared by nucleo-
philic substitution from O-p-toluene sulfonyl
glycofurano/pyranoses using sodium azide in anhydrous
DMF under inert condition. The deoxy-azido sugars
were further subjected to CuAAC reaction with p--
vanillin based terminal alkynes, to afford triazolyl p-
vanillin-glycoconjugates in excellent yields. The reaction
time has been significantly reduced (10 min) under mi-
crowave heating.
3-Methoxy-4-(prop-2-ynyloxy) benzaldehyde (2) White
1
solid; mp = 68-70 °C; H NMR (400 MHz, CDCl3): δ 9.86
(s, 1H), 7.47–7.43 (m, 3H), 4.86–4.85 (m, 2H), 3.93 (s, 3H),
2.57 (t, J = 1.5 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
190.5, 152.0, 149.9, 130.8, 126.3, 112.5, 110.2, 56.9, 56.0;
MS: m/z 191 [M + H]+.
General procedure for synthesis of vanillyl alcohol (3)
Experimental
The compound p-vanillin was reduced with NaBH4 in dry
THF at room temperature to afford compound 3 [27].
General methods
General procedure for synthesis
of 2-methoxy-1-(prop-2-ynyloxy)-4-((prop-2-ynyloxy)
methyl) benzene (4)
All of the reactions were executed using anhydrous solvents
under an argon atmosphere in 1 h oven-dried glassware at
100 °C. All reagents and solvents were of pure analytical grade.
Thin-layer chromatography (TLC) was performed on 60 F254
silica gel, pre-coated on aluminum plates and revealed with
either a UV lamp (λmax = 254 nm) or a specific color reagent
(iodine vapors) or by spraying with methanol-H2SO4 solution
To a solution of vanillyl alcohol 3 (3.2 g, 20.75 mmol) in
DMF (30 mL), caesium carbonate (2.4 equiv., 16.23 g,
49.82 mmol) and propargyl bromide (2.6 equiv., 4.8 mL,
53.95 mmol) were added under inert condition. The reaction
mixture was stirred for 12 h at room temperature. After com-
pletion of reaction (monitored by TLC), reaction mixture was
in vacuo concentrated, extracted with CH2Cl2, and washed
twice with 10 % Na2CO3, water, and brine solution. The or-
ganic layer was dried over anhydrous Na2SO4. The residue
obtained after removal of the solvent was purified by flash
column chromatography using gradient mixtures of n-hex-
ane-ethyl acetate as eluent to afford compound 4.
1
and subsequent heating at 60 °C. H and 13C NMR spectra
were recorded at 300 and 75 MHz, respectively. Chemical
shifts given in ppm downfield from internal TMS; J values in
Hz. Mass spectra were recorded using electrospray ionization
mass spectrometry (ESI-MS). Infrared spectra were obtained as
Nujol mulls in KBr plates. Elemental analysis was performed
using a C, H, N analyzer, and results were found to be within
0.4 % of the calculated values. Reaction under microwave
condition was carried out on Microwave CEM Discover R
Lab Mate.
2 - m e t h o x y - 1 - ( p ro p - 2 - y n y l o x y ) - 4 - ( ( p ro p - 2 -
1
ynyloxy)methyl)benzene) (4) Yellow liquid; H NMR
General procedure for synthesis of sugar azides (1)
(300 MHz, CDCl3): δ 7.01–6.87 (m, 3H), 4.75, (s, 2H), 4.55
(s, 2H), 4.16 (s, 2H), 3.88 (s, 3H), 2.49 (s, 1H), 2.47 (s, 1H);
13C NMR (75 MHz, CDCl3): δ 155.0, 149.6, 147.0, 129.0,
121.1, 113.9, 112.1, 78.3, 75.9, 69.7, 56.6, 55.9; MS: m/z 231
[M + H]+.
The compounds 1a-i were prepared from readily available
carbohydrates (D-glucose, D-galactose, D-ribose etc.) using
standard protection and modification methodologies [25, 26].

Glycoconj J
Table 3 Synthesis of vanillin glycoconjugates 6 via CuAAC reaction
3
Entrya
Sugar azides
1b
Click productb
Yield (%)c
Yield (%)d
1
90
92
6b
2
1c
91
90
6c
3
1d
90
90
6d
4
1f
89
90
6f
5
6
1g
85
88
87
88
3
6g
1h
6h
a Molar ratios: deoxy-azido sugar 1 (2.4 equiv), vanillin alkyne 4 (1.0 equiv), CuI (0.5 equiv) and DIPEA (1.0 equiv)
b Triazolyl vanillin-glycoconjugates
c Isolated yield at rt. (time 10 h)
d Isolated yield through reaction under microwave at 100 °C with a stirring rate 200 rpm in 10 min

Glycoconj J
Scheme 2 Click inspired
synthesis of vanillin containing
glycomacrocycle
General procedure for synthesis of triazolyl
glycoconjugates 5
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-2,3,4-tri-O-acetyl-β-D-xylopyranose (5a)
Yellowish solid (231 mg, yield 94 %); mp = 140-142 °C; IR
(KBr) νmax: 3210, 3132, 2937, 2870, 1668, 1591, 1511, 1461,
1428, 1301, 1265, 1154, 730, 629 cm−1; 1H NMR (300 MHz,
CDCl3): δ 9.83 (s, 1H), 7.92 (s, 1H), 7.43–7.32 (m, 2H), 7.16
(d, J = 8.7, 1H), 5.84 (d, J = 8.4, 1H), 5.46–5.37 (m, 4H),
5.19–5.14 (m, 1H), 4.31–4.26 (m, 1H), 3.92 (s, 3H), 3.65–
3.58 (m, 1H), 2.07 (s, 3H), 2.04 (s, 3H), 1.83 (s, 3H); 13C
NMR (75 MHz, CDCl3): δ 190.7, 169.6, 169.5, 168.7,
152.6, 149.8, 130.4, 126.3, 121.5, 112.5, 109.2, 86.1, 71.7,
70.2, 68.1, 65.3, 62.4, 55.8, 29.4, 20.4, 20.3, 19.9; MS: m/z
492 [M + H]+; Anal. Calcd for C22H25N3O10: C, 53.77; H,
5.13; N, 8.55. Found: C, 54.16; H, 4.8; N, 8.8.
A solution of 2 (95.1 mg, 0.5 mmol) and azido-sugars 1a (1.2
eqv, 0.6 mmol) in presence of DIPEA (0.087 ml, 0.5 mmol)
and CuI (47.6 mg, 0.25 mmol) in dry CH2Cl2 were stirred at
room temperature under inert atmosphere for 10 h. After com-
pletion of reactions (monitored by TLC), the reaction mixtures
were in vacuo concentrated to obtain crude residues, which
were further purified by silica gel (100–200 mesh) column
chromatography to afford compounds 5a.
An equimolar mixture of azido-sugars 1a (1.2 eqv,
0.6 mmol) and compound 2 (95.1 mg, 0.5 mmol) in anhy-
drous toluene (10 ml) in presence of DIPEA (0.087 ml,
0.5 mmol) and CuI (47.6 mg, 0.25 mmol) were heated at
100 °C for 10 min in a microwave reactor (Microwave CEM
Discover R Lab Mate). After completion (monitored by TLC),
the reaction mixtures were in vacuo concentrated, extracted
with CH2Cl2, washed with water, and dried over anhydrous
Na2SO4 followed by in vacuo concentration. Purification
using flash column chromatography afforded triazolyl O-van-
illin glycoconjugate 5a.
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-methyl-5-deoxy-2,3-O-isopropylidene-β-D-
ribofuranoside (5b) Yellow liquid (193 mg, yield 92 %); IR
(KBr) νmax: 3205, 3135, 2937, 2860, 1670, 1590, 1510, 1465,
1
1425, 1255, 1148, 730, 626 cm−1; H NMR (300 MHz,
CDCl3): δ 9.84 (s, 1H), 7.79 (s, 1H), 7.44–7.41 (m, 2H),
7.28–7.22 (m, 1H), 5.38 (s, 2H), 5.00–4.41 (m, 6H), 3.92 (s,
3H), 3.36 (s, 3H), 1.45 (s, 3H), 1.30 (s, 3H); 13C NMR
(75 MHz, CDCl3): δ 190.8, 152.9, 149.8, 143.3, 130.4,
126.6, 123.5, 112.8, 112.4, 110.0, 109.9, 109.0, 84.9, 81.6,
62.7, 55.9, 55.5, 53.1, 26.2, 24.7; MS: m/z 420 [M + H]+;
Anal. Calcd for C20H25N3O7: C, 57.27; H, 6.01; N, 10.02.
Found: C, 57.56; H, 6.28; N, 10.35.
CHO
OH
N
N
N
N
O
O
HO
HO
HO
O
O
N
OH
O
OCH3
N
N
N
HO
HO
O
HO
HO
O
N
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-
galactopyranose (5c) Yellow liquid (214 mg, yield 90 %); IR
(KBr) νmax: 3190, 3129, 2932, 2865, 1667, 1592, 1515, 1468,
1427, 1268, 1153, 735, 628 cm−1;1H NMR (300 MHz,
CDCl3): δ 9.83 (s, 1H), 7.84 (s, 1H), 7.43–7.40 (m, 2H),
7.23–7.20 (m, 1H), 5.49–5.29 (m, 3H), 4.63–4.61 (m, 2H),
4.48–4.32 (m, 2H), 4.19–4.17 (m, 2H), 3.91 (s, 3H), 1.47 (s,
3H), 1.35 (s, 6H), 1.28 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
190.8, 153.0, 149.9, 142.7, 130.4, 126.6, 124.4, 112.6, 109.8,
108.9, 96.2, 70.9, 70.5, 70.1, 66.9, 62.6, 55.8, 50.4, 25.8, 24.7,
HO
N
OH
8
7
O
N
N
N
OH
O
N
HO
HO
N
HO
O
OH
HO
H3CO
N
N
N
OCH3
HO
O
OH
O
HO
O
N
N
OH
N
HO
10
9
HO
Fig. 3 Structure of deprotected glycoconjugates 7–10

Glycoconj J
24.2; MS: m/z 475 [M + H]+; Anal. Calcd for C23H29N3O8: C,
58.10; H, 6.15; N, 8.84. Found: C, 57.73; H, 5.85; N, 8.53.
CDCl3): δ 9.82 (s, 1H), 7.73 (s, 1H), 7.42–7.20 (m, 8H),
5.97–5.96 (m, 1H), 5.32 (s, 2H), 4.72–4.63 (m, 3H), 4.54–
4.43 (m, 3H), 3.98–3.97 (m, 1H), 3.87 (s, 3H), 1.42 (s, 6H),
1.30 (m, 3H); 13C NMR (75 MHz, CDCl3): δ 190.6, 152.8,
149.6, 142.8, 136.5, 130.2, 128.4, 128.0, 127.7, 126.4, 124.2,
112.3, 111.8, 109.0, 104.9, 81.6, 81.3, 78.4, 77.4, 71.7, 62.4,
55.6, 49.1, 26.4, 25.9; MS: m/z 496 [M + H]+; Anal. Calcd for
C26H29N3O7: C, 63.02; H, 5.90; N, 8.48. Found: C, 63.35; H,
6.16; N, 8.29.
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-methyl-2,3,4-tri-O-benzyl-6-deoxy-α-D-glu-
copyranose (5d) Yellowish solid (313 mg, yield 92 %);
mp = 90-92 °C; IR (KBr) νmax 3215, 3137, 2936, 2870,
1670, 1590, 1520, 1463, 1440, 1275, 1160, 728, 636 cm−1;
1H NMR (300 MHz, CDCl3): δ 9.81 (s, 1H), 7.70 (s, 1H),
7.40–7.18 (m, 18H), 5.37–5.28 (m, 2H), 4.98–4.48 (m, 9H),
4.01–3.90 (m, 5H), 3.39–3.37 (m, 1H), 3.16–3.07 (m, 4H);
13C NMR (75 MHz, CDCl3): δ 190.8, 152.9, 149.8, 143.1,
138.3, 137.8 (2), 130.5, 128.4 (2), 128.1, 127.9, 127.7, 126.6,
124.5, 112.5, 109.1, 98.0, 97.9, 81.8, 81.7, 79.8, 75.7, 74.9,
73.4, 73.2, 68.9, 62.8, 62.7, 56.0, 55.9, 55.1, 50.7, 29.6; MS:
m/z 680 [M + H]+; Anal. Calcd for C39H41N3O8: C, 68.91; H,
6.08; N, 6.18. Found: C, 69.22; H, 5.81; N, 5.79.
General procedure for synthesis of triazolyl
glycoconjugates 6
A solution of compound 4 (58 mg, 0.25 mmol) and azido-
sugars 1b (2.4 eqv, 0.6 mmol) in presence of DIPEA
(0.087 ml, 0.5 mmol) and CuI (47.6 mg, 0.25 mmol) in dry
CH2Cl2 were stirred at room temperature under inert atmo-
sphere for 10 h. After completion of reactions (monitored by
TLC), the reaction mixtures were in vacuo concentrated to
obtain crude residues which were further purified by silica
gel (100–200 mesh) column chromatography to afford com-
pounds 6b.
An equimolar mixture of azido-sugars 1b (1.2 eqv,
0.3 mmol) and compound 4 (29 mg, 0.125 mmol) in
anhydrous toluene (10 ml) in presence of DIPEA
(0.044 ml, 0.25 mmol) and CuI (24 mg, 0.125 mmol)
were heated at 100 °C for 10 min in a microwave (MW)
reactor (Microwave CEM Discover R Lab Mate). After
completion (monitored by TLC), the reaction mixtures
were in vacuo concentrated, extracted with CH2Cl2,
washed with water, and dried over anhydrous Na2SO4
followed by in vacuo concentration. Purification using
flash column chromatography afforded triazolyl
glycoconjugates 6b.
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-3-O-benzyl-6-deoxy-1,2-O-isopropylidene-α-
D-glucofuranose (5e) Yellowish solid (236 mg, yield 90 %);
mp = 52-54 °C; IR (KBr) νmax: 3205, 3135, 2931, 2876, 1665,
1600, 1522, 1460, 1430, 1263, 1157, 733, 628 cm−1; 1H NMR
(300 MHz, CDCl3): δ 9.82 (s, 1H), 7.78 (s, 1H), 7.42–7.18 (m,
8H), 5.93 (d, J = 3.3, 1H), 5.31 (s, 2H), 4.75–4.51 (m, 4H),
4.39–4.35 (m, 2H), 4.08 (s, 1H), 3.93–3.89 (m, 4H), 1.41 (s,
3H), 1.31 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 190.9,
152.9, 149.7, 142.6, 137.0, 130.4, 128.5, 128.1, 127.7,
126.6, 125.0, 112.3, 111.9, 109.1, 105.2, 105.0, 82.0, 81.0,
80.1, 72.1, 67.4, 62.5, 55.8, 55.7, 53.9, 26.6, 26.1; MS: m/z
526 [M + H]+; Anal. Calcd for C27H31N3O8: C, 61.70; H,
5.95; N, 8.00. Found: C, 62.04; H, 6.34; N, 8.31.
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose
(5f) Yellow liquid (262 mg, yield 93 %); IR (KBr) νmax: 3210,
3140, 2930, 2868, 1666, 1597, 1517, 1461, 1444, 1262, 1153,
729, 632 cm−1; 1H NMR (300 MHz, CDCl3): δ 9.85 (s, 1H),
7.98 (s, 1H), 7.45–7.42 (m, 2H), 7.19–7.16 (m, 1H), 5.88 (d,
J = 9.3, 1H), 5.54 (t, J = 9.6, 2H), 5.38 (s, 2H), 5.30–5.24 (m,
1H), 4.25–4.14 (m, 3H), 3.94 (s, 3H), 2.21 (s, 3H), 2.04 (s,
3H), 2.00 (s, 3H), 1.84 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
190.8, 170.2, 169.8, 169.6, 168.9, 152.8, 149.9, 143.8, 130.6,
126.4, 121.7, 112.6, 109.3, 86.2, 86.1, 73.9, 70.6, 67.7, 66.8,
66.7, 62.8, 62.6, 62.5, 61.1, 56.0, 55.9, 20.5, 20.3, 20.1; MS:
m/z 564 [M + H]+; Anal. Calcd for C25H29N3O12: C, 53.29; H,
5.19; N, 7.46. Found: C, 53.49; H, 5.51; N, 7.83.
1-(4-((2-methoxy-4-((methyl-5-deoxy-2,3-O-
isopropylidene-β-D-ribofuranosyl)-1H-1,2,3-triazol-4-
yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-methyl-5′-deoxy-2′,3′-O-isopropylidene-β-D-
ribofuranose (6b) Yellow liquid (155 mg, yield 90 %); IR
(KBr) νmax: 3138, 2955, 2937, 2910, 2874, 2637, 1613, 1443,
1422, 1378, 1212, 1174, 1111, 934, 829, 757, 710, 606 cm−1;
1H NMR (300 MHz, CDCl3): δ 7.74 (s, 1H), 7.67 (s, 1H),
7.00–6.83 (m, 3H), 5.29–5.27 (m, 2H), 5.01–5.00 (m, 2H),
4.754.41 (m, 12H), 3.85 (s, 3H), 3.37 (s, 3H), 3.35 (s, 3H),
1.49 (s, 3H), 1.30 (s, 6H), 1.26 (s, 3H); 13C NMR (75 MHz,
CDCl3): δ 149.5, 147.0, 145.1, 144.2, 131.3, 123.2, 123.1,
122.8, 120.3, 113.9, 112.7, 111.6, 109.9, 85.0, 84.9, 84.8,
81.6, 72.1, 63.1, 63.0, 55.7, 55.3, 52.9, 31.7, 29.1, 26.1 (2),
24.7 (2); MS: m/z 689 [M + H]+; Anal. Calcd for
C32H44N6O11: C, 55.80; H, 6.44; N, 12.20. Found: C, 56.13;
H, 6.13; N, 12.39.
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-3-O-benzyl-1,2-O-isopropylidine-α-D-
xylofuranose (5 g) Yellow liquid (228 mg, yield 92 %); IR
(KBr) νmax: 3217, 3135, 2927, 2856, 1660, 1591, 1519, 1457,
1
1453, 1261, 1167, 728, 631 cm−1; H NMR (300 MHz,

Glycoconj J
1-(4-((2-methoxy-4-( (6-deoxy-1, 2:3, 4-di-O-
isopropylidene-α-D-galactopyranosyl)-1H-1,2,3-triazol-4-
yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-6′-deoxy-1′,2′:3′,4′-di-O-isopropylidene-α-D-
galactopyranose (6c) Yellow liquid (182 mg, yield 91 %); IR
(KBr) νmax: 3135, 2957, 2942, 2915, 2867, 2640, 1605, 1450,
1423, 1370, 1215, 1178, 1110, 932, 831, 755, 716, 610 cm−1;
1H NMR (300 MHz, CDCl3): δ 7.79 (s, 1H), 7.73 (s, 1H),
7.00–6.92 (s, 2H), 6.85–6.82 (d, J = 8.4 Hz, 1H), 5.51 (t,
J = 4.8, 2H), 5.27 (s, 2H), 4.66–4.58 (m, 6H), 4.49–4.40 (m,
4H), 4.32 (m, 2H), 4.21–4.15 (m, 4H), 3.86 (s, 3H), 1.48 (s,
6H), 1.38 (s, 3H), 1.37 (s, 3H), 1.34 (s, 3H), 1.28 (s, 6H), 1.25
(s, 3H); 13C NMR (75 MHz, CDCl3): δ 149.61, 147.2, 144.6,
143.8, 131.3, 124.1, 124.1, 123.8, 123.8, 120.4, 114.1, 111.7,
109.7, 109.7, 108.9, 96.1, 71.9, 71.0, 70.9, 70.6, 70.2, 67.1,
67.0, 63.2, 55.8, 50.3, 29.5 (2), 25.8, 24.7, 24.3; MS: m/z 801
[M + H]+; Anal. Calcd for C38H52N6O13: C, 56.99; H, 6.54;
N, 10.49. Found: C, 56.69; H, 6.33; N, 10.75.
977 [M + H]+; Anal. Calcd for C42H52N6O21: C, 51.64; H,
5.37; N, 8.60. Found: C, 51.26; H, 5.6; N, 8.91.
1-(4-((2-methoxy-4-((3-O-benzyl-1,2-O-isopropylidine-α-
D - x y l o f u r a n o s e ) - 1 H - 1 , 2 , 3 - t r i a z o l - 4 -
yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-3′-O-benzyl-1′,2′-O-isopropylidine-α-D-xylofuranosyl
(6 g) Yellowish solid (179 mg, yield 85 %); mp = 48-50 °C; IR
(KBr) νmax: 3136, 2957, 2931, 2929, 2878, 2633, 1621, 1443,
1418, 1377, 1212, 1175, 932, 827, 754, 608 cm−1; 1H NMR
(300 MHz, CDCl3): δ 7.66 (s, 1H), 7.58 (s, 1H), 7.33–7.32 (m,
10H), 7.00–6.83 (m, 3H), 5.97–5.94 (m, 2H), 5.27–5.24 (m,
3H), 4.74–4.42 (m, 15H), 3.99 (m, 2H), 3.84 (s, 3H), 1.42 (s,
6H), 1.30 (m, 6H); 13C NMR (75 MHz, CDCl3): δ 149.6,
147.1, 144.9, 144.0, 136.7, 131.3, 128.5, 128.1, 127.8,
124.0, 123.6, 123.6, 120.4, 114.1, 111.9, 111.6, 105.1, 81.8,
81.4, 78.7, 78.6, 72.2, 71.8, 63.2, 63.1, 55.7, 49.1, 49.0, 26.6,
26.0; MS: m/z 841 [M + H]+; Anal. Calcd for C44H52N6O11:
C, 62.84; H, 6.23; N, 9.99. Found: C, 62.47; H, 6.44; N, 9.8.
1-(4-((2-methoxy-4-((methyl-2,3,4-tri-O-benzyl-6-deoxy-
α - D - g l u c o p y r a n o s y l ) - 1 H - 1 , 2 , 3 - t r i a z o l - 4 -
yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-methyl-2′,3′,4′-tri-O-benzyl-6′-deoxy-α-D-glucopyra-
nose (6d) Yellowish solid (272 mg, yield 90 %); mp = 65-
67 °C; IR (KBr) νmax: 3131, 2960, 2940, 2920, 2865, 2647,
1610, 1455, 1427, 1378, 1220, 1176, 1148, 938, 840, 756,
720, 618 cm−1; 1H NMR (300 MHz, CDCl3): δ 7.67 (s, 1H),
7.57 (s, 1H), 7.32–7.30 (m, 15H), 6.97–6.81 (m, 3H), 5.26 (m,
4H), 4.99–4.87 (m, 4H), 4.81–4.68 (m, 6H), 4.62–4.47 (m,
14H), 3.98 (m, 2H), 3.83 (s, 3H), 3.42–3.39 (m, 2H), 3.18 (s,
3H), 3.09 (s, 3H). 13C NMR (75 MHz, CDCl3): δ 149.4,
147.0, 144.8, 144.0, 138.2, 137.7, 131.2, 128.3, 128.2,
128.0, 127.8, 127.7, 127.5, 124.1, 123.9, 120.2, 113.7,
111.5, 97.8 (2), 81.6, 79.7, 75.5, 74.7, 73.2, 71.9, 68.9, 63.1,
63.0, 55.7, 55.1, 55.0, 50.5, 50.4. MS: m/z 1209 [M + H]+;
Anal. Calcd for C70H76N6O13: C, 69.52; H, 6.33; N, 6.95.
Found: C, 69.81; H, 5.95; N, 7.27.
1-(4-((2-methoxy-4-((2,3,4,6-tetra-O-acetyl-β-D-
g a l a c t o p y r a n o s y l ) - 1 H - 1 , 2 , 3 - t r i a z o l - 4 -
yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-2′,3′,4′,6′-tetra-O-acetyl-D-galactopyranosyl (6 h)
Yellowish solid (215 mg, yield 88 %); mp = 48-50 °C; IR
(KBr) νmax: 3137, 2954, 2940, 2918, 2870, 2637, 1612,
1443, 1421, 1377, 1221, 1182, 929, 830, 751, 610 cm−1; 1H
NMR (300 MHz, CDCl3): δ 7.94 (s, 1H), 7.86 (s, 1H), 7.02–
6.87 (m, 3H), 5.85–5.82 (m, 2H), 5.58–5.54 (m, 4H), 5.27–
5.23 (m, 4H), 4.76–4.68 (m, 2H), 4.57–4.52 (m, 4H), 4.21–
4.15 (m, 4H), 3.89 (s, 3H), 2.22 (s, 6H), 2.04–2.00 (s, 12H),
1.89 (s, 3H), 1.86 (s, 3H); 13C NMR (75 MHz, CDCl3): δ
170.2, 169.9, 169.7, 168.9, 158.9, 149.7, 147.2, 145.8,
144.8, 131.6, 131.0, 121.4, 121.0, 120.7, 120.3, 114.2,
111.8, 86.1, 79.5, 75.7, 74.6, 73.9, 72.2, 71.3, 70.7, 67.8,
67.7, 66.8, 63.1, 61.1, 56.8, 56.7, 55.8, 20.5, 20.4 (2), 20.1;
MS: m/z 977 [M + H]+; Anal. Calcd for C42H52N6O21: C,
51.64; H, 5.37; N, 8.60. Found: C, 51.91; H, 5.71; N, 8.83.
1-(4-((2-methoxy-4-((2,3,4,6-tetra-O-acetyl-β-D-
g l u c o o p y r a n o s y l ) - 1 H - 1 , 2 , 3 - t r i a z o l - 4 -
yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-triazol-1-
yl)-2′,3′,4′,6′-tetra-O-acetyl-β-D-glucoopyranosyl (6f)
Yellowish solid (217 mg, yield 89 %); mp = 138-140 °C; IR
(KBr) νmax: 3140, 2951, 2938, 2926, 2861, 2650, 1613, 1447,
1421, 1371, 1210, 1180, 928, 831, 750, 610 cm−1; 1H NMR
(300 MHz, CDCl3): δ 7.94 (s, 1H), 7.87 (s, 1H), 6.96–6.87 (m,
3H), 5.95 (m, 2H), 5.47 (m, 4H), 5.26 (m, 4H), 4.67 (s, 2H),
4.49 (s, 2H), 4.27–4.07 (m, 6H), 3.87 (s, 3H), 2.06–2.03 (m,
18H), 1.86–1.83 (m, 6H); 13C NMR (75 MHz, CDCl3): δ
170.25, 169.6, 169.1, 168.6, 149.5, 147.0, 145.6, 144.7,
131.3, 121.3, 120.9, 120.3, 114.1, 111.7, 85.3, 74.7, 72.4,
71.9, 70.1, 67.5, 62.8, 61.3, 55.6, 20.3, 20.2, 19.8; MS: m/z
General procedure for synthesis of triazolyl
glycoconjugate 6i
A solution of compouind 4 (115 mg, 0.5 mmol) and azido-
sugars 1i (1.2 eqv, 0.6 mmol) in presence of DIPEA (0.087 ml,
0.5 mmol) and CuI (47.6 mg, 0.25 mmol) in dry CH2Cl2 were
stirred at room temperature under inert atmosphere for 10 h.
After completion of reactions (monitored by TLC), the reac-
tion mixtures were in vacuo concentrated to obtain crude res-
idues which were further purified by silica gel (100–200
mesh) column chromatography to afford compounds 6i.
Bis-triazolyl-tetra-O-acetyl-D-mannitol macrocycle (6i)
Yellowish liquid (262 mg, yield 78 %); IR (KBr) νmax: 3216,

Glycoconj J
3139, 2936, 2857, 1667, 1590, 1524, 1470, 1440, 1262, 1145,
730, 636 cm−1; 1H NMR (300 MHz, CDCl3): δ 7.62–7.59 (m,
2H), 6.79–6.72 (m, 3H), 5.27–5.14 (m, 6H), 4.54 (m, 3H),
4.36 (s, 2H), 3.73 (s, 3H), 3.64–3.61 (m, 2H), 3.07–3.04 (m,
1H), 2.05–1.83 (m, 12H); 13C NMR (75 MHz, CDCl3): δ
169.5, 169.4, 169.3, 169.1, 149.3, 146.8, 144.3, 131.2,
123.6, 123.3, 120.3, 113.7, 111.6, 71.8, 68.2, 67.7, 62.8,
55.6, 54.1, 49.8, 20.5, 20.4, 20.3, 20.1; MS: m/z 631 [M +
H]+; Anal. Calcd for C42H52N6O21: C, 53.33; H, 5.43; N,
13.33. Found: C, 52.72; H, 5.64; N, 13.04.
158.9, 148.8, 146.8, 142.1, 131.1, 125.5, 119.9, 113.1, 111.5,
73.4, 70.069.2, 61.6, 57.2, 55.3, 54.9, 53.0, 48.6, 45.8, 41.3;
MS: m/z 463 [M + H]+; Anal. Calcd for C42H52N6O21: C,
51.94; H, 5.67; N, 18.17. Found: C, 52.27; H, 6.04; N, 18.56.
General procedure for deprotection
of isopropylidene protected triazolyl glycoconjugates
Isopropylidene protected triazolyl glycoconjugate 6c was
deprotected by reaction with trifluoroacetic acid in water for
2 h to afford compound 10 using the protocol described by
Prasad et al. [29].
General procedure for deprotection of acetyl-protected
triazolyl glycoconjugates
Acetyl protected triazolyl glycoconjugates were deprotected
by reaction with sodium methoxide in anhydrous methanol for
24 h using the protocol described by Agoston et al. [28].
1-(4-((2-methoxy-4-((D-galactopyranosyl)-1H-1,2,3-
triazol-4-yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-α-D-galactopyranose (10) Viscous liquid; IR
(KBr) νmax: 3141, 2953, 2948, 2916, 2853, 2648, 1611,
1443, 1430, 1356, 1221, 1182, 1105, 938, 827, 757, 719,
1-(5-((4-formyl-2-methoxyphenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-β-D-xylopyranose (7) White solide; mp = 136-
138 °C; IR (KBr) νmax: 3274, 2918, 2854, 2355, 1661, 1585,
1510, 1410, 1268, 1133, 1046, 1005, 820, 721 cm−1; 1H NMR
(400 MHz, DMSO-d6): δ 9.85 (s, 1H), 8.48 (s, 1H), 7.59–7.56
(m, 1H), 7.42–7.40 (m, 2H), 5.53–5.37 (m, 3H), 5.27–5.21
(m, 3H), 3.85–3.75 (m, 4H), 3.48–3.47 (s, 1H); 13C NMR
(100 MHz, DMSO-d6): δ 191.4, 152.7, 149.2, 141.8, 129.8,
125.8, 124.3, 112.4, 109.5, 88.1, 77.0, 71.9, 69.0, 68.3, 61.5,
55.4; MS: m/z 366 [M + H]+; Anal. Calcd for C42H52N6O21:
C, 52.60; H, 5.57; N, 11.50. Found: C, 52.99; H, 5.64; N,
11.31.
1
618 cm−1; H NMR (400 MHz, DMSO-d6): δ 8.18 (s, 1H),
8.17 (s, 1H), 7.11–7.05 (m, 1H), 6.92–6.90 (m, 1H), 6.84–
6.80 (m, 1H), 5.07–5.04 (m, 4H), 4.90–4.90 (m, 1H), 4.52–
4.47 (m, 2H), 4.41 (s, 2H), 4.31–4.26 (m, 2H), 4.21–4.19 (m,
1H), 3.91–3.89 (m, 1H), 3.73–3.71 (m, 3H), 3.63–3.60 (m,
2H), 3.38–3.31 (m, 5H); 13C NMR (100 MHz, DMSO-d6): δ
148.7, 146.1, 142.3, 135.3, 119.9, 118.4, 113.2, 110.5, 97.1,
92.5, 73.4, 72.8, 71.4, 69.5, 68.8, 68.2, 62.6, 61.5, 57.1, 55.2,
51.0, 48.5; MS: m/z 641 [M + H]+; Anal. Calcd for
C38H52N6O13: C, 48.75; H, 5.66; N, 13.12. Found: C, 49.01;
H, 5.29; N, 13.51.
Acknowledgments VKT thank Council of Scientific and Industrial
Research (CSIR), New Delhi (Grant No. 02/(0173)/13/EMR-II) for the
funding and CISC, Department of Chemistry, Banaras Hindu University,
Varanasi for the spectral data of developed molecules. PD thanks
Department of Science and Technology (DST), New Delhi for the support
of this research under Women Scientist-A scheme (SR/WOS-A/CS-83/
2011 (G) dated 17.07.2012).
1-(4-((2-methoxy-4-((β-D-glucoopyranosyl)-1H-1,2,3-
triazol-4-yl)methoxy)methyl)phenoxy)methyl)-1H-1,2,3-
triazol-1-yl)-β-D-glucopyranose (8) Viscous liquid; IR
(KBr) νmax: 3152, 2930, 2851, 2348, 1520, 1504, 1424,
1254, 1120, 1038, 960, 826, 728 cm−1; 1H NMR (400 MHz,
DMSO-d6): δ 8.45 (s, 1H), 8.34 (s, 1H), 7.15–7.13 (m, 1H),
6.94–6.88 (m, 2H), 5.57–5.51 (m, 2H), 5.10 (s, 2H), 4.55 (s,
2H), 4.47 (s, 2H), 3.81–3.67 (m, 12H), 3.46–3.39 (m, 6H),
3.26–3.22 (m, 2H); 13C NMR (100 MHz, DMSO-d6): δ 149.2,
147.3, 144.2, 142.9, 131.4, 124.5, 123.7, 120.5, 113.3, 112.1,
87.9, 80.4 (2), 77.3, 72.5, 72.4, 71.6, 69.9, 62.9, 61.8, 61.1,
55.8; MS: m/z 641 [M + H]+; Anal. Calcd for C42H52N6O21:
C, 48.75; H, 5.66; N, 13.12. Found: C, 48.48; H, 5.99; N,
12.78.
Compliance with ethical standards
Conflicts of interest The authors declare that they have no conflicts of
interest.
Ethical approval This article does not contain any studies with human
participants or animals performed by any of the authors.
References
Bis-triazolyl-D-mannitol macrocycle (9) Viscous liquid; IR
(KBr) νmax: 3222, 3136, 2940, 2842, 1570, 1506, 1461, 1438,
1252, 1149, 735, 638 cm−1; 1H NMR (400 MHz, DMSO-d6):
δ 8.14 (s, 1H), 7.88 (s, 1H), 7.10 (m, 1H), 6.89–6.81 (m, 2H),
5.08–5.05 (m, 3H), 4.95–4.91 (m, 2H), 4.73–4.70 (m, 4H),
4.49–4.48 (m, 2H), 4.31–4.29 (m, 3H), 3.83–3.81 (m, 3H),
3.72–3.70 (m, 4H); 13C NMR (100 MHz, DMSO-d6): δ 160.5,
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