Synthesis and biological evaluation of novel glycosyl-containing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives as acetylcholinesterase inhibitors

Article abstract of DOI:10.3184/174751917X15064232103047

An efficient protocol for the synthesis of novel glycosyl-containing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives starting from the commercially available d-glucosamine hydrochloride is described by reaction of glycosyl isothiocyanate with various aminotriazoles in DMF. Glycosyl isothiocyanate is an important intermediate and synthetic methods are discussed. The acetylcholinesterase inhibitory activity of these compounds was tested by Ellman’s method. It was found that most compounds exhibited over 90% inhibition and they were subsequently evaluated for their IC₅₀values.

Full text of DOI:10.3184/174751917X15064232103047

JOURNAL OF CHEMICAL RESEARCH 2017
VOL. 41 OCTOBER, 571–575
RESEARCH PAPER 571
Synthesis and biological evaluation of novel glycosyl-containing
1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives as acetylcholinesterase
inhibitors
Xiu-Jian Liua, Lei Wanga, Long Yina, Feng-Chang Chengb, Hui-Min Suna, Wei-Wei Liua,c,d*,
Da-Hua Shia,c and Zhi-Ling Caoa,c
aCollege of Pharmaceutical Sciences, Huaihai Institute of Technology, Lianyungang 222005, P.R. China
bChina University of Mining and Technology, Xuzhou 221116, P.R. China
cJiangsu Institute of Marine Resources, Lianyungang 222005, P.R. China
dJiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Huaihai Institute of Technology, Lianyungang 222005, P.R. China.
An efficient protocol for the synthesis of novel glycosyl-containing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives starting from the
commercially available d-glucosamine hydrochloride is described by reaction of glycosyl isothiocyanate with various aminotriazoles in
DMF. Glycosyl isothiocyanate is an important intermediate and synthetic methods are discussed. The acetylcholinesterase inhibitory
activity of these compounds was tested by Ellman’s method. It was found that most compounds exhibited over 90% inhibition and they
were subsequently evaluated for their IC50 values.
Keywords: synthesis, glycosyl, 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole, acetylcholinesterase inhibitory activity
Results and discussion
Chemistry
Carbohydrates have long interested chemists and biochemists
as a large natural resource due to their predominant role in
biological and industrial applications.1–4 As an energy source
and as a compound in many metabolic processes, sugars are
present in every part of the human body. d-glucosamine is a
naturally occurring amino sugar,5,6 is one of the most abundant
monosaccharides and has been widely used as an alternative
medicine for the prevention and/or treatment of rheumatoid
arthritis and osteoarthritis7,8. Furthermore, d-glucosamine and
its derivatives exhibit a broad variety of bioactivities, such as
anti-inflammatory,9 antibacterial,10 anti-cancer11 and anti-
acetylcholinesterase.12
Heterocyclic compounds have wide application due to
their good pharmacological activity, and the discovery of
heterocyclic compounds with novel structures may lead to
new drugs and treatments for a variety of diseases.13–15 In
the literature, nitrogen-containing heterocyclic compounds
have been shown to have a broad range of pharmaceutical
activities. 1,2,4-Triazoles and their derivatives are commonly
utilised heterocyclic pharmacophores that present numerous
biological activities, such as antiproliferative,16 antibacterial,17
antioxidant,18 antitubercular19 and anti-acetylcholinesterase.20
Moreover, numerous recent studies have reported on the
synthesis and pharmacological action of fused heterocycles.
Various 1,2,4-triazoles and their fused heterocyclic
derivatives have received considerable attention due to their
synthetic and biological importance. For example, the fused
1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives show various
biological properties, such as antimicrobial,21 anti-tumour,22
antibacterial,23 analgesic24 and anti-inflammatory,25 and have
cholinesterase inhibitory activity.26
To develop a simple synthetic pathway to the novel glycosyl-
containing 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole compounds,
glycosyl isothiocyanate30 was a critical intermediate in this
approach. Our strategy began with an attempted synthesis of
glycosyl isothiocyanate without protection of the hydroxyl
groups using d-glucosamine hydrochloride in different ways.
However, the glycosyl isothiocyanate was not obtained by
this strategy. We speculated that the hydroxyl groups of the
d-glucosamine interfered with reactions. Based on our previous
work,31 the benzyl group was selected to protect the hydroxyl
groups. We found that from 1,3,4,6-tetra-O-benzyl-β-d-
glucosamine hydrochloride 1, via the salts 2, 2-isothiocyanate-
1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-glucopyranose
3
can
be synthesised in high yields. Treatment of compounds 1
with triethylamine in acetonitrile was followed by addition
of carbon disulfide dropwise via a syringe into the reaction
mixture with stirring at 0 °C. The mixture was stirred for 2 h
to give dithiocarbamic acid salts 2. Subsequent reaction with
tosyl chloride (p-TsCl) yielded the key glycosyl isothiocyanate
intermediate 3 (Scheme 1).
Reaction of the arylhydrazide 4 with carbon disulfide
and potassium hydroxide in anhydrous ethanol afforded the
required dithiocarbazinate 5. This salt underwent ring closure
with an excess of hydrazine hydrate to give the 4-amino-5-aryl-
4H-1,2,4-triazole-3-thiol 6 (Scheme 2).23
The glycosyl isothiocyanate 3 was treated with various
aminotriazoles 6 to yield the 3-aryl-6-glycosyl-1,2,4-triazolo-
[3,4-b]1,3,4-thiadiazoles 7 in anhydrous dimethylformamide
(DMF), and the desired compounds 7a–h were obtained
by extraction (Scheme 3). We tried to remove the benzyl
protecting groups by using palladium on activated charcoal.32
Unfortunately, the target product was not obtained. A possible
explanation is that compound 7a contains sulfur, which might
contribute to the failure in use of Pd/C.
Some studies have used molecular hybrid-based approaches
to find new compounds with diverse biological activities.27–29
Based on the above ideas, and in an attempt to discover new
potent acetylcholinesterase (AChE) inhibitors, we designed
and synthesised
a
series of novel glycosyl-containing
Based on previous work31, we then converted the isothiocyanate
into a thiocarbamide, which reacted with acyl bromide to give
the thiazole. We used a similar method to synthesise glycosyl
isothiocyanate 3. However, here we did not use the acyl halide
1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives. The synthesised
derivatives were evaluated by Ellman’s method to screen for a
novel AChE inhibitor and explore the AChE inhibitory activity of
the compounds compared with d-glucosamine hydrochloride.
* Correspondent. E-mail: liuww323@aliyun.com

572 JOURNAL OF CHEMICAL RESEARCH 2017
OBn
H
O
O
N
H
O
NaOH
p-methoxybenzaldehyde
O
N
BnO
BnO
H
O
NaH, BnBr
OBn
H
O
H
O
O
H
O
o
H
O
NH H l
H
O
-
0 C r.t.
H2O, r.t.
·
C
2
O
O
OBn
OBn
5mol L–1 HCl
Et3N, CS2
0 oC
TsCl
0 oC - r.t.
OBn
O
O
NH
BnO
BnO
BnO
BnO
O
acetone, reflux
OBn
C
OBn
BnO
BnO
·
NH H l
OBn
2
S
N
CS
S
Et3NH
3
1
2
Scheme 1 Synthetic pathways of glycosyl isothiocyanate.
N
N
O
O
·
NH2NH2 H
H
2O
CS2
K H
K
N
S
NH2
r
A
H
S
r
A
r
A
N
N
N
O
H
H
NH2
6
S
4
5
6a Ar = C6H5
6e Ar = 4-IC6H4
6f Ar = 3-C5H4N
6g Ar = 2-C4H3S
6b Ar = 2-ClC6H4
6c Ar = 3-OCH3C6H4
6d Ar = 4-OHC6H4
6h Ar = 4-(N,N-di-Me)-C6H4
Scheme 2 Synthesis of the 4-amino-5-aryl-4H-1,2,4-triazole-3-thiol.
OBn
S
OBn
O
N
N
BnO
DMF
O
OBn
BnO
BnO
BnO
+
r
A
H
S
NH
N
OBn
N
CS
NH2
N
N
N
N
r
A
3
6
7
7a Ar = C6H5
7b Ar = 2-ClC6H4
7e Ar = 4-IC6H4
7f Ar = 3-C5H4N
7c Ar = 3-CH3OC6H4
7d Ar = 4-HOC6H4
7g Ar = 2-C4H3S
7h Ar = 4-(N,N-di-Me)-C6H4
Scheme 3 Synthesis of the desired product.
in the process of cyclisation, resulting in a process that is
more environmentally friendly and less harmful. It is easy and
expeditious to obtain 3-aryl-6-glycosyl-1,2,4-triazolo[3,4-
b]1,3,4-thiadiazoles 7 and involves the reaction of glycosyl
isothiocyanate 3 and aminotriazoles 6. As d-glucosamine and its
derivatives play an important role in biomedical research, these
novel compounds were tested for their biological activity.
As shown in Table 1, it was found that six of the eight desired
compounds exhibited over 90.0% inhibition and these were
subsequently evaluated for their IC50 values. Tacrine was used
as a reference compound. The results indicated that all of the
compounds had higher inhibitory activity against AChE than
the precursor d-glucosamine hydrochloride. The best compound
7a showed high activity with an IC50 of 2.464 0.522 (mean
SD) against AChE and inhibited AChE with a dose-dependent
relationship (Fig. 1). In addition, the compounds 4-amino-5-
phenyl-4H-1,2,4-triazole-3-thiol and 1,3,4,6-tetra-O-benzyl-β-
d-glucosamine hydrochloride showed weak inhibitory activity
against AChE compared with compound 7a, indicating that
the presence of the 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole unit
improved the AChE inhibitory activity. These data can be used
to orient the choice of scaffold for the design of AChE inhibitors.
Biological activity
The AChE inhibitory activity of the synthesised compounds
was evaluated in vitro by Ellman’s method,33 in which the AChE
extracts from electric eel were used. Their inhibitory potency
was described as the inhibition rate and the half maximal
inhibitory concentration, IC50. The results are summarised in
Table 1.

JOURNAL OF CHEMICAL RESEARCH 2017 573
Table 1 In vitro inhibitory activity of the synthesised compounds against AChE
Inhibition
Compound
Ar
Inhibition (%)a
IC50 (μM)b
7a
7b
7c
7d
7e
7f
7g
7h
C6H5
2-ClC6H4
3-CH3OC6H4
4-HOC6H4
4-IC6H4
3-C5H4N
2-C4H3S
4-(N,N-di-Me)-C6H4
97.55
96.50
93.53
87.59
91.80
96.04
96.32
83.51
14.46
10.12
46.23
2.464 0.522
3.514 0.323
5.679 0.655
6.412 1.233
4.992 0.689
–
3.655 0.213
7.785 1.567
–
d-Glucosamine hydrochloride
–
–
–
4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol
1,3,4,6-Tetra-O-benzyl-β-d-glucosamine hydrochloride
Tacrine
aInhibition activity at 50 μg mL .
bValues are means SD, n = 3.
–
–
0.269 0.004
−1
hydrochloric acid (7 mL, 5 N) to afford a white solid after refluxing for
1 h and then cooling. The mixture was filtered and washed with acetone to
give 1,3,4,6-tetra-O-benzyl-β-d-glucosamine hydrochloride 1 as: White
amorphous powder; yield 76%; m.p. 144–146 °C; IR (KBr) (υ, cm−1): 3027,
2925, 1502, 1455, 1066, 738, 696; 1H NMR (400 MHz, DMSO-d6): δ 8.38
(s, 3H, NH2HCl), 7.50–7.23 (m, 18H, ArH), 7.15 (dd, J = 6.6, 2.9 Hz, 2H,
ArH), 4.81 (dd, J = 16.7, 9.8 Hz, 4H, H1Glu, CH2Ph), 4.73–4.62 (m, 2H,
CH2Ph), 4.61–4.48 (m, 3H, CH2Ph), 3.85 (dd, J = 10.0, 8.6 Hz, 1H, H4Glu),
3.76–3.56 (m, 4H, H6aGlu, H6bGlu, H5Glu, H3Glu), 3.06 (dd, J = 9.8, 8.8 Hz, 1H,
H2Glu).
60
40
2-Isothiocyanate-1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-glucopyranose (3)
Triethylamine (3 mmol) was added to a solution of 1,3,4,6-tetra-
O-benzyl-β-d-glucosamine hydrochloride 1 (1 mmol, 1 equiv.) in
acetonitrile (15 mL) and the mixture was cooled in an ice bath. Carbon
disulfide (1 mmol) was then added dropwise to the reaction mixture via
a syringe pump. The mixture was stirred for 2 h. Then tosyl chloride
(p-TsCl) (1 mmol) was added with cooling from an external ice bath.
The mixture was stirred for another 0.5 h. The crude product was
recrystallised from ethanol to give compound 3 as: White amorphous
powder; yield 90%; m.p. 55–56 °C; IR (KBr) (υ, cm−1): 3433, 3030,
2873, 2078, 1454, 1359, 1313, 1068; 1H NMR (400 MHz, DMSO-d6): δ
7.45–7.25 (m, 18H, ArH), 7.24–7.17 (dd, J = 7.3, 1.9 Hz, 2H, ArH), 4.81
(dd, J = 16.7, 9.8 Hz, 4H, H1Glu, CH2Ph), 4.73–4.62 (m, 2H, CH2Ph),
4.61-–4.48 (m, 3H, CH2Ph), 3.95–3.81 (m, 3H, H4Glu, H6aGlu, H6bGlu),
3.67–3.54 (m, 3H, H5Glu, H3Glu, H2Glu). HRMS (ESI) m/z calcd for
C35H35NNaO5S [M + Na]+: 604.2128; found: 604.2130.
0.5
Concentration (ug mL–1)
Fig. 1 Dose-dependent inhibition of compound 6a against AChE. Values
are means SD, n = 3.
Experimental
All chemicals were purchased from commercial sources and used
without further purification unless otherwise stated. Melting
points were determined on a Yanaco melting point apparatus and
were uncorrected. IR spectra were recorded on a Bruker Tensor 27
spectrometer with KBr pellets. 1H NMR spectra were recorded on a
Bruker Avance 400 MHz at ambient temperature using DMSO-d6 as
solvent and TMS as an internal standard. Chemical shifts are reported
in ppm. HRMS (ESI) analysis was performed on an Agilent 6230 mass
spectrometer. Flash column chromatography was performed on silica
200–300 mesh.
Synthesis of 4-amino-5-aryl-4H-1,2,4-triazole-3-thiol (6)
Potassium hydroxide (0.56 g, 10 mmol) was added to a solution of
aryl hydrazide 4 (10 mmol) in methanol (25 mL) at 0 °C with stirring.
Carbon disulfide (0.5 mL) was then added slowly and the reaction
mixture was stirred and monitored by TLC. After reaction completion,
the solid product potassium dithiocarbazinate 5 was filtered, washed
with chilled methanol and dried. Without any purification, potassium
dithiocarbazinate 5 was dissolved in water (20 mL) and hydrazine
hydrate (1 mL) was added. The mixture was heated under reflux until
the reaction was complete, and then diluted with a little cold water and
acidified with conc. hydrochloric acid. The white precipitated solid 6
was filtered, washed with cold water and recrystallised from aqueous
methanol.
2-Amino-1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-glucopyranose
hydrochloride (1)
NaOH (1.86 g, 46.5 mmol) was added to a solution of d-glucosamine
hydrochloride (10 g, 46.4 mmol) in water (70 mL) at room temperature with
stirring, and 15 min later, p-methoxybenzaldehyde (5.7 mL, 46.6 mmol) was
added dropwise. The reaction mixture was stirred at ambient temperature
for an additional 24 h, after which the resulting white solid was filtered
and washed with water (500 mL) to afford 2-(4-methoxybenzylidene)-2-
deoxy-β-d-glucopyranose (11.4 g, 83%). NaH (60%, 5 g, 125 mmol) was
added portionwise to a mixture of 2-(4-methoxybenzylidene)-2-deoxy-
β-d-glucopyranose (6.6 g, 22.2 mmol) and BnBr (14 mL, 117.9 mmol) in
DMF (50 mL) at 0 °C. The reaction mixture was allowed to attain room
temperature and stirred for 12 h. After reaction completion, the solution was
diluted with a large amount of water and extracted with CH2Cl2 (3 × 50 mL).
The solvent was removed under reduced pressure to give a yellow viscous
liquid. A solution of the yellow liquid in acetone (100 mL) was treated with
Synthesis of 3-aryl-6-glycosyl-1,2,4-triazolo[3,4-b]1,3,4-thiadiazoles
(7a–h); general procedure
4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol 6 (1.7 mmol) was added
to a solution of glycosyl isothiocyanate 3 (1.7 mmol) in DMF (20 mL)
at 110 °C. The reaction mixture was stirred and monitored by TLC.

574 JOURNAL OF CHEMICAL RESEARCH 2017
After reaction completion, the solution was diluted with a large amount
of water and extracted with CH2Cl2 to give the crude product, which
was then purified by column chromatography on silica gel (EtOAc/
petroleum ether) to give the pure products 7a–h.
(m, 4H, CH2Ph), 4.62–4.52 (m, 4H, CH2Ph), 3.84–3.69 (m, 3H, H4Glu
,
H6aGlu, H6bGlu), 3.65–3.55 (m, 3H, H5Glu, H3Glu, H2Glu). HRMS (ESI)
m/z calcd for C42H41N6O5S [M + H]+: 741.2854; found: 741.2860.
3-(4-Dimethylaminophenyl)-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-
β-d-glucopyranose-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(7g): White amorphous powder; yield 76%; m.p. 102–103 °C; IR (KBr)
(υ, cm−1): 3424, 3214, 3027, 2862, 1614, 1585, 1489, 1359, 1263, 1197,
1060; 1H NMR (400 MHz, DMSO-d6): δ 8.59 (d, J = 8.4 Hz, 1H, NH),
7.97 (d, J = 8.9 Hz, 2H, ArH), 7.42–7.27 (m, 8H, ArH), 7.26–7.16 (m,
6H, ArH), 7.16–7.07 (m, 6H, ArH), 6.84 (d, J = 9.1 Hz, 2H, ArH), 4.84
(d, J = 12.5 Hz, 1H, H1Glu), 4.80–4.67 (m, 4H, CH2Ph), 4.64–4.52 (m,
4H, CH2Ph), 3.86–3.70 (m, 3H, H4Glu, H6aGlu, H6bGlu), 3.68–3.58 (m,
3H, H5Glu, H3Glu, H2Glu), 2.97 (s, 6H, N(CH3)2). HRMS (ESI) m/z calcd
for C45H47N6O5S [M + H]+: 783.3323; found: 783.3319.
3-Phenyl-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-glucopyranose-2-
yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (7a): White amorphous
powder; yield 75%; m.p. 148–150 °C; IR (KBr) (υ, cm−1): 3441, 3027,
2865, 1605, 1466, 1358, 1052; 1H NMR (400 MHz, DMSO-d6): δ
8.69 (d, J = 8.6 Hz, 1H, NH), 8.13 (d, J = 7.4 Hz, 2H, ArH), 7.52 (ddd,
J = 11.1, 9.6, 6.0 Hz, 3H, ArH), 7.42–7.27 (m, 8H, ArH), 7.25–7.15 (m,
6H, ArH), 7.14–7.04 (m, 6H, ArH), 4.83 (d, J = 12.5 Hz, 1H, H1Glu),
4.79–4.67 (m, 4H, CH2Ph), 4.64–4.53 (m, 4H, CH2Ph), 3.90–3.57 (m,
6H, H4Glu, H6aGlu, H6bGlu, H5Glu, H3Glu, H2Glu). HRMS (ESI) m/z calcd
for C43H42N5O5S [M + H]+: 740.2901; found: 740.2890.
3-(2-Chlorophenyl)-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-
glucopyranose-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (7b):
White amorphous powder; yield 66%; m.p. 134–135 °C; IR (KBr) (υ,
cm−1): 3449, 3060, 3027, 2876, 1626, 1496, 1471, 1361, 1147, 1054;
1H NMR (400 MHz, DMSO-d6): δ 8.25 (d, J = 9.3 Hz, 1H, –NH),
7.78 (dd, J = 7.6, 1.8 Hz, 1H, ArH), 7.65 (dd, J = 7.9, 1.1 Hz, 1H, ArH),
7.58–7.47 (m, 2H, ArH), 7.40–7.27 (m, 8H, ArH), 7.26–7.13 (m, 12H,
ArH), 4.83 (d, J = 12.5 Hz, 1H, H1Glu), 4.79–4.63 (m, 4H, CH2Ph),
4.62–4.51 (m, 4H, CH2Ph), 3.84–3.68 (m, 3H, H4Glu, H6aGlu, H6bGlu),
3.63–3.50 (m, 3H, H5Glu, H3Glu, H2Glu). HRMS (ESI) m/z calcd for
C43H41ClN5O5S [M + H]+: 774.2511; found: 774.2507.
3-Thienyl-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-glucopyranose-2-
yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (7h): Yellow amorphous
powder; yield 65%; m.p. 172–174 °C; IR (KBr) (υ, cm−1): 3441, 3299,
3026, 2867, 1583, 1492, 1468, 1453, 1145, 1066; 1H NMR (400 MHz,
DMSO-d6): δ 8.71 (d, J = 8.5 Hz, 1H, NH), 7.75 (d, J = 5.0 Hz, 2H,
ArH), 7.43–7.28 (m, 8H, ArH), 7.27–7.14 (m, 7H, ArH), 7.13–7.03 (m,
6H, ArH), 4.82 (d, J = 12.5 Hz, 1H, H1Glu), 4.79–4.65 (m, 4H, CH2Ph),
4.64–4.53 (m, 4H, CH2Ph), 3.95–3.70 (m, 3H, H4Glu, H6aGlu, H6bGlu),
3.69–3.57 (m, 3H, H5Glu, H3Glu, H2Glu). HRMS (ESI) m/z calcd for
C41H40N5O5S2 [M + H]+: 746.2465; found: 746.2458.
In vitro cholinesterase activity assay
3-(3-Methoxyphenyl)-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-
AChE inhibitory activity were measured through Ellman’s
colorimetric method with a slight modification.33 Electric eel AChE
was dissolved in phosphate-buffered saline (PBS, 0.1 M, pH 8.0)
to obtain a solution of 0.35 U mL−1. In the assays, AChE (20 μL) was
incubated with the test compound (10 μL) and phosphate-buffered
saline (130 μL, 0.1 M, pH 8.0) for 10 min in 96-well microplates
before addition of DTNB solution (20 μL, 3.33 mM) and ATCI
solution (20 μL, 5.30 mM). After addition of DTNB and ATCI, the
96-well microplates were read at 412 nm with a microplate reader
(SPECTRAFLUOR, TECAN, Sunrise, Austria) for 15 min. One
triplicate sample without inhibitors was always present to yield 100%
AChE activity. The reaction rates were compared and the percentage
inhibition due to the presence of the test compounds was calculated.
Tacrine was used as a reference drug. All samples were assayed in
triplicate.
glucopyranose-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
(7c):
White amorphous powder; Yield 70%; m.p. 159–160 °C; IR (KBr) (υ,
cm−1): 3442, 3201, 3028, 2899, 1604, 1578, 1485, 1454, 1392, 1282,
1
1220, 1126, 1062; H NMR (400 MHz, DMSO-d6); δ 8.71 (d, J = 8.4
Hz, 1H, NH), 7.73 (d, J = 7.8 Hz, 1H, ArH), 7.66 (s, 1H, ArH), 7.47 (t, J
= 8.0 Hz, 1H, ArH), 7.42–7.27 (m, 8H, ArH), 7.25–7.13 (m, 6H, ArH),
7.12–7.01 (m, 7H, ArH), 4.82 (d, J = 12.5 Hz, 1H, H1Glu), 4.79–4.66 (m,
4H, CH2Ph), 4.63–4.53 (m, 4H, CH2Ph), 3.78 (s, 3H, OCH3), 3.79–3.68
(m, 3H, H6aGlu, H6bGlu, H4Glu), 3.64–3.54 (m, 3H, H5Glu, H3Glu, H2Glu).
HRMS (ESI) m/z calcd for C44H44N5O6S [M + H]+: 770.3007; found:
770.3010.
3-(4-Hydroxylphenyl)-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-
glucopyranose-2-yl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (7d):
White amorphous powder; yield 67%; m.p. 126–128 °C; IR (KBr) (υ,
cm−1): 3442, 3201, 3028, 2899, 1604, 1578, 1485, 1454, 1392, 1282,
1
1220, 1126, 1062; H NMR (400 MHz, DMSO-d6): δ: 9.95 (s, 1H,
Acknowledgements
–OH), 8.61 (d, J = 9.1 Hz, 1H, –NH), 7.95 (d, J = 8.7 Hz, 2H, ArH),
7.43–7.26 (m, 9H, ArH), 7.25–7.15 (m, 5H, ArH), 7.14–7.06 (m, 5H,
ArH), 6.92 (d, J = 8.7 Hz, 2H, ArH), 4.83 (d, J = 12.5 Hz, 1H, H1Glu),
4.78–4.65 (m, 4H, CH2Ph), 4.63–4.53 (m, 4H, CH2Ph), 3.85–3.70 (m,
3H, H4Glu, H6aGlu, H6bGlu), 3.63–3.50 (m, 3H, H5Glu, H3Glu, H2Glu).
HRMS ESI m/z calcd for C43H42N5O6S [M + H]+: 756.2850; found:
756.2855.
This work was supported by the Project Funded by the Priority
Academic Development Program of Jiangsu Higher Education
Institutions, Natural Science Foundation of Jiangsu Province
(BK20151281), Open-end Funds of Jiangsu Key Laboratory
of Marine Biotechnology (HS2014007), the Science and
Technology Project of Lianyungang (CG1415) and Public
Science and Technology Research Funds Projects of Ocean
(201505023).
3-(4-Iodinylphenyl)-6-(1,3,4,6-tetra-O-benzyl-2-deoxy-β-d-
glucopyranose-2-yl)-[1,2,4]trazolo[3,4-b][1,3,4]thiadiazole
(7e):
White amorphous powder; yield 71%; m.p. 178–179 °C; IR (KBr) (υ,
cm−1): 3441, 3196, 3026, 2939, 1580, 1473, 1392, 1278, 1207, 1062;
1H NMR (400 MHz, DMSO-d6): δ 8.72 (d, J = 8.6 Hz, 1H, NH), 7.94
(d, J = 8.6 Hz, 2H, ArH), 7.89 (d, J = 8.4 Hz, 2H, ArH), 7.42–7.27 (m,
8H, ArH), 7.25–7.12 (m, 6H, ArH), 7.11–7.03 (m, 6H, ArH), 4.82 (d, J
= 12.5 Hz, 1H, H1Glu), 4.79–4.65 (m, 4H, CH2Ph), 4.63–4.53 (m, 4H,
CH2Ph), 3.90–3.69 (m, 3H, H4Glu, H6aGlu, H6bGlu), 3.68–3.55 (m, 3H,
H5Glu, H3Glu, H2Glu). HRMS (ESI) m/z calcd for C43H41IN5O5S [M +
H]+: 866.1868; found: 866.1870.
Received 19 June 2017; accepted 31 August 2017
Paper 1704837
https://doi.org/10.3184/174751917X15064232103047
Published online: 4 October 2017
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