Synthesis and biological evaluation of novel C1-glycosyl thiazole derivatives as acetylcholinesterase inhibitors

Article abstract of DOI:10.3184/174751916X14711768865726

A new series of C1-glycosyl thiazole derivatives was synthesised by the reaction of 1-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-yl)thiourea with 2-bromoacetophenone derivatives. Subsequent removal of the acetyl groups were conducted using NaOMe-MeOH. The structures of all new products were confirmed by IR, ¹H NMR and HRMS (ESI). The acetylcholinesterase inhibitory activities of these new compounds were tested. Among them, N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(4-nitrophenyl)-1,3-thiazole-2-amine showed the best activity with an inhibition rate of 43.21%.

Full text of DOI:10.3184/174751916X14711768865726

JOURNAL OF CHEMICAL RESEARCH 2016
VOL. 40 SEPTEMBER, 545–548
RESEARCH PAPER 545
Synthesis and biological evaluation of novel C1-glycosyl thiazole derivatives
as acetylcholinesterase inhibitors
Long Yina, Feng–Chang Chengb, Qu–Xiang Lib, Wei–Wei Liua,c,d*, Xiu–Jian Liua Zhi–Ling Caoa,c and
Da–Hua Shia,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
A new series of C1-glycosyl thiazole derivatives was synthesised by the reaction of 1-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-
2-yl)thiourea with 2-bromoacetophenone derivatives. Subsequent removal of the acetyl groups were conducted using NaOMe–MeOH. The
structures of all new products were confirmed by IR, 1H NMR and HRMS (ESI). The acetylcholinesterase inhibitory activities of these new
compounds were tested. Among them, N-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-4-(4-nitrophenyl)-1,3-thiazole-2-
amine showed the best activity with an inhibition rate of 43.21%.
Keywords: C1-glycosyl thiazole, synthesis, acetylcholinesterase inhibitory activities
Recent years have witnessed a burgeoning interest in the
chemistry of carbohydrates, which results from the unique
role played in many biological processes.1–4 As an energy
source and an element of many metabolic processes, sugars
are present in every part of the human body. D-Glucosamine
is a naturally occurring amino sugar,5,6 one of the most
abundant monosaccharides, and has been widely used as
an alternative prevention and/or treatment of rheumatoid
arthritis and osteoarthritis.7,8 Furthermore, D-glucosamine
and its derivatives exhibit a broad variety of bioactivities such
as anti-inflammatory,9 anti-cancer,10 antibacterial11 and anti-
acetylcholinesterase properties.12
In the literature, sulfur-containing N-heterocyclic compounds
possess a broad range of pharmaceutical activities. Thiazoles
and their derivatives are commonly utilised heterocyclic
pharmacophores, which are an important class of heterocyclic
molecules presenting numerous biological activities such as
antifungal,13 anticancer,14 antiviral,15 antibacterial16 and xanthine
oxidase inhibitors.17 Moreover, recent studies have shown that
a number of compounds containing the thiazole skeleton act
as cholinesterase inhibitors for the treatment of Alzheimer’s
disease (AD).18–20
evaluated by Ellman’s method in order to screen a novel AChE
inhibitor and explore the influence of the GlcNAc unit against
AChE-inhibition activity.
Results and discussion
To develop a simple synthetic pathway to glycosyl thiazole
compounds, glycosyl thiourea 3 was a critical intermediate
in this reaction. First, glycosyl chloride 1 was synthesised
according to the literature.21,22 Treatment of compounds
1
with potassium thiocyanate in refluxing acetonitrile
efficiently provided 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-
β-D-glucopyranosyl isothiocyanate 2. Subsequent reaction
with ammonia yielded the key glycosyl thiourea immediate 3
(Scheme 1).
The corresponding acetophenone derivatives
4 were
brominated by treatment with CuBr2 in refluxing ethyl acetate
and chloroform, and the desired compounds 5a–5j were
obtained by extraction. Cyclisations of the glycosyl thiourea 3
with the 2-bromoacetophenones were completed by refluxing in
EtOH for 0.5 h to give the glycosyl thiazole derivatives 6a–6j in
high yield. Compound 6a was efficiently deprotected to give the
hydroxyl derivative 7a (Scheme 2) in the presence of NaOMe–
MeOH. The structures of newly synthesised compounds were
To date, researchers have been interested in molecular
hybrid-based approaches to find some new compounds with
potential biological activities. Based on the above ideas, and, in
an attempt to discover new potent acetylcholinesterase (AChE)
inhibitors; we designed and synthesised a series of novel C1-
glycosyl thiazole derivatives. The synthesised derivatives were
1
confirmed by their IR and H NMR spectra and by HRMS
(ESI).
In the IR spectra, characteristic absorption bands for
compounds 6 for the fragments: C=O and C–O–C were
visible in the ranges of: 1660–1750 cm−1 and 1035–1042 cm−1,
AcO
H
O
H
O
O
O
O
AcCl
RT
Ac2O
TEA, MeOH, 0oC
H
O
H
O
AcO
AcO
H
H
O
O
·
H
H
O
O
H l
C
NH
NHAc
NH2
l
C
O
1
AcO
AcO
O
O
H
N
KSCN
(n-C4H9)4NHSO4, MeCN
Ammonia
RT
N
CS
NH2
AcO
AcO
AcO
AcO
NHAc
NHAc
3
o
S
2
4
molecular sieves
A
Scheme 1 Synthetic pathways of glycosyl thiourea.
* Correspondent. E-mail: liuww323@aliyun.com

546 JOURNAL OF CHEMICAL RESEARCH 2016
O
O
CuBr2
Br
EtOAc, CHCl3, reflux
Ar
Ar
5a j
−
4
OAc
OAc
O
EtOH
reflux
H
H
+
NH2
OAc
N
AcO
AcO
O
AcO
AcO
O
N
N
Ar
Br
Ar
NHAc
NHAc
S
S
3
5a j
6a j
−
−
OH
NaOMe/MeOH
RT
H
H
N
N
AcO
AcO
O
HO
HO
O
N
N
Ar
Ar
NHAc
NHAc
S
S
6a j
7a j
−
−
Ar = a
: C6H5,
f
: 4-ClC6H4,
b
g
: 4-CH3C6H4,
: 4-BrC6H4,
c
h
H4
,
: 4-CH3OC6H4,
: 4-NO2C6
d
i
j
: 3-CH3OC6H4,
: 3-NO2C6H4,
: Biphenyl-4-yl
e
: 4-FC6H4,
Scheme 2 Synthesis of the desired product.
Table
1 The acetylcholinesterase-inhibition activities of glycosyl
respectively. There were moderate intensity bands in the
region 3307–3429 cm−1 corresponding to ν (N–H) whilst the
band for ν (C–H) appeared in the region 2853–2926 cm−1.
The FTIR peaks of compound 7a showed a strong band at
3424–3460 cm−1 characteristic of hydroxyl groups. Meanwhile,
in 7a the stretching vibration in the region 1745–1750 cm−1,
disappeared which can be attributed to the hydrolysis of ester
groups. In addition, compounds 6 and 7a displayed νcyclic (C=N)
and νcyclic (C=C) for the thiazole ring at 1529–1549 cm−1 and
1436–1490 cm−1, respectively.
thiadiazole derivatives
Compound
R
C6H5
4-MeC6H4
4-MeOC6H4
3-MeOC6H4
4-FC6H4
Inhibition/%a
24.65
19.34
17.46
22.83
<10
6a
6b
6c
6d
6e
6f
6g
6h
6i
4-ClC6H4
4-BrC6H4
4-NO2C6H4
3-NO2C6H4
Biphenyl-4-yl
<10
39.74
43.21
31.59
<10
1
In the H NMR spectra, all the compounds 6a–j showed a
characteristic triplet within the 5.29–5.56 ppm region, with the
coupling constant in the range J = 9.2–9.7 Hz, which indicated
that sugar ring possessed a β-configuration because the H1
proton of the pyranose ring was coupled to the C2–H and
N–H protons whilst the signals of the other glycosyl protons
resonated in the range 3.89–5.30 ppm. In compound 7a, the
presence of one singlet (CH3) was observed at 1.83 ppm, which
demonstrated that all of the hydroxyl protecting groups had
been removed. However, the chemical shift of the pyranose
6j
7a
mb
nc
C6H5
29.65
19.72
14.46
_
_
aThe inhibition activities of the compounds at the concentration of 50 μg mL–1.
bm stands for 4-(C6H5)C6H4-1,3-thiazole-2-amine.
cn stands for D-glucosamine hydrochloride.
1
ring protons varied little. The H NMR spectra of the newly
As shown in Table 1, compared with the AChE-inhibition
activity of the compounds m and n, the majority of the screened
compounds displayed AChE-inhibition activity, indicating
that the presence of a thiazole moiety improved activities of
the GlcNAc unit. Among them, compounds 6g and 6h with
4-bromophenyl and 4-nitrophenyl substituents represented
moderate AChE-inhibition activity, 39.74% and 43.21%,
respectively. Compared with compound 6a, the deprotected
compound, 7a, increased AChE-inhibition activity, suggesting
that the removal of hydroxyl protection groups also improved
activities to a certain extent. In summary, this information
has provided us with a guideline to find new kinds of AChE
inhibitors.
synthesised compound 7a showed all of the expected proton
resonances and integration values.
In the mass spectra (ESI), the compounds 6 and 7a all showed
molecular ion peaks for [M + Na]+ or [M + K]+, so indicating
that this type of compound easily combine with metal ions. The
detailed results of IR, 1H NMR, and HRMS (ESI) are presented
in the experimental part.
Biological activity
The AChE-Inhibition activities of the newly synthesised
compounds were evaluated in vitro by Ellman’s method23, in
which the AChE extracts from electric eel were used. Their
inhibitory potency was described as the inhibition rate. The
results are summarised in Table 1.

JOURNAL OF CHEMICAL RESEARCH 2016 547
Experimental
NH), 7.72 (d, J = 6.4 Hz, 2H, ArH), 7.19 (d, J = 8.1 Hz, 2H, ArH), 7.13
(s, 1H, Thiazole), 5.29 (t, J = 9.5 Hz, 1H, H-1), 5.21 (t, J = 9.9 Hz, 1H,
H-3), 4.85 (t, J = 9.8 Hz, 1H, H-4), 4.19 (dd, J = 12.3, 4.9 Hz, 1H, H-6),
4.00–3.90 (m, 3H, H-2, H-5, H-6’), 2.33 (s, 3H, CH3), 1.99–1.75 (m,
12H, 4 × CH3); HRMS (ESI) m/z calcd for: C24H29N3NaO8S [M + Na]+
542.1568; found: 542.1574.
All chemicals were purchased from commercial sources and used
without further purification unless otherwise stated. All reactions were
monitored by TLC. TLC plates were detected with 254 nm UV light.
Melting points were determined on a Yanaco melting point apparatus
and were uncorrected. IR spectra were recorded on a Bruker Tensor 27
1
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(4-methoxyphenyl)-1,3-thiazole-2-amine (6c): Yellow solid; yield
0.492 g (92%); m.p. 100–101 °C; IR (nmax/cm–1) KBr: 3351, 2929, 1747,
spectrometer with KBr pellets. H NMR were recorded with Bruker
Avance at 400 Hz using TMS as an internal standard and DMSO-d6
or D2O as a solvent. HRMS (ESI) analysis was performed on a
Agilent 6500 mass spectrometer. Flash column chromatography was
performed on silica 200–300 mesh.
1
1660, 1543, 1242, 1036, 907; H NMR (400 MHz, DMSO-d6) δ 8.55
(d, J = 7.5 Hz, 1H, NH), 7.80 (d, J = 8.8 Hz, 1H, NH), 7.76 (d, J = 8.7
Hz, 2H, ArH), 7.10 (s, 1H, Thiazole), 6.94 (d, J = 8.8 Hz, 2H, ArH),
5.47 (m, 1H, H-1), 5.41 (d, J = 11.4 Hz, 1H, H-3), 4.91 (t, J = 9.6 Hz,
1H, H-4), 4.32 (m, 1H, H-6), 4.05–3.93 (m, 3H, H-2, H-5, H-6’), 3.77
(s, 3H, CH3),1.98–1.81 (m, 12H, 4 × CH3). HRMS (ESI) m/z calcd for:
C24H29N3NaO9S [M + Na]+ 558.1517; found: 558.1530.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(3-methoxyphenyl)-1,3-thiazole-2-amine (6d): Yellow solid;
yield 0.482 g (90%); m.p. 82–83 °C; IR (nmax/cm–1) KBr: 3374, 2932,
1748, 1658, 1539, 1235, 1040, 916; 1H NMR (400 MHz, DMSO-d6)
δ 8.58 (d, J = 7.2 Hz, 1H, NH), 7.79 (d, J = 8.8 Hz, 1H, NH), 7.40
(dd, J = 10.4, 5.1 Hz, 2H, ArH), 7.29 (dd, J = 9.1, 6.8 Hz, 1H, ArH),
7.24 (s, 1H, Thiazole), 6.86 (dd, J = 9.1, 7.9 Hz, 1H, ArH), 5.45 (t,
J = 9.2 Hz, 1H, H-1), 5.42 (t, J = 9.8 Hz, 1H, H-3), 4.92 (t, J = 9.6 Hz,
1H, H-4), 4.31 (m, 1H, H-6), 4.05–3.92 (m, 3H, H-2, H-5, H-6’), 3.79
(s, 3H, CH3), 1.99–1.75 (m, 12H, 4 × CH3); HRMS (ESI) m/z calcd for:
C24H29N3NaO9S [M + Na]+ 558.1517; found: 558.1526.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(4-fluorophenyl)-1,3-thiazole-2-amine (6e): White solid; yield
0.455 g (87%); m.p. 82–83 °C; IR (nmax/cm–1) KBr: 3400, 2931, 1746,
1653, 1545, 1490, 1229, 1041, 906; 1H NMR (400 MHz, DMSO-d6) δ
8.40 (d, J = 9.2 Hz, 1H, NH), 8.05 (d, J = 8.8 Hz, 1H, NH), 7.87 (m,
2H, ArH), 7.23 (m, 2H, ArH), 7.19 (s, 1H, Thiazole), 5.30 (t, J = 9.5 Hz,
1H, H-1), 5.22 (t, J = 9.4 Hz, 1H, H-3), 4.86 (t, J = 9.8 Hz, 1H, H-4),
4.21 (dd, J = 12.5, 4.6 Hz, 1H, H-6), 4.04–3.92 (m, 3H, H-2, H-5,
H-6’), 1.99–1.76 (m, 12H, 4 × CH3); HRMS (ESI) m/z calcd for:
C23H26FN3NaO8S [M + Na]+ 546.1317; found: 546.1327.
2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl
isothiocyanate (2)
A mixture of KSCN (0.58 g, 6 mmol), tetra-n-butylammonium
hydrogen sulfate (0.34 g, 1 mmol), and molecular sieves (4 Å, 3.0 g)
in anhydrous acetonitrile (30 mL) was stirred at room temperature for
2.5 h and then treated with glycosyl chloride 1 (1.1 g, 3 mmol). The
mixture was heated under reflux until the reaction was completed, as
judged by TLC analysis. The resultant suspension was filtered, and
the filtrate was concentrated. The residue was purified by column
chromatography (silica gel, EtOAc-hexanes) to afford 2 as a white
solid; yield 0.97 g (83%); m.p. 156–157 °C; IR (nmax/cm–1) KBr:
1
3436, 2928, 2074, 1749, 1661, 1232, 1082, 910; H NMR (400 MHz,
DMSO-d6) δ 8.25 (d, J = 9.4 Hz, 1H, NH), 5.36 (d, J = 9.2 Hz, 1H, H-1),
5.11 (t, J = 9.3 Hz, 1H, H-3), 4.90 (t, J = 9.7 Hz, 1H, H-4), 4.12–4.05 (m,
4H, H-2, H-5, H-6, H-6’), 2.03–1.82 (m, 12H, 4 × CH3); HRMS (ESI)
m/z calcd for: C15H20N2NaO8S [M + Na]+ 411.0833; found: 411.0844.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)
thiourea (3)
Glycosyl isothiocyanate 3 (0.388 g, 1 mmol) was dissolved in CH2Cl2
(20 mL), then ammonia was passed though the CH2Cl2 solution in
room temperature for 1.5 h. After the reaction, CH2Cl2 was removed
to give the product 3 as a white powder; yield 0.381 g (94%); m.p.
203–204 °C; IR (nmax/cm–1) KBr: 3464, 2934, 1747, 1658, 1225, 1045,
1
911; H NMR (400 MHz, DMSO-d6) δ 8.09 (d, J = 9.3 Hz, 1H, NH)
7.90 (m, 1H, NH), 5.48 (m, 1H, H-1), 5.08 (m, 1H, H-3), 4.82 (t, J = 9.7
Hz, 1H, H-4), 4.20 (d, J = 21.1 Hz, 1H, H-6), 3.96–3.74 (m, 3H, H-2,
H-5, H-6’), 1.99–1.76 (m, 12H, 4 × CH3); HRMS (ESI) m/z calcd for:
C15H23N3NaO8S [M + Na]+ 428.1098; found: 428.1106.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(4-chlorophenyl)-1,3-thiazole-2-amine (6f): Pale yellow solid;
yield 0.453 g (84%); m.p. 96–97 °C; IR (nmax/cm–1) KBr: 3371,
1
2936, 1748, 1661, 1545, 1475, 1233, 1040, 908; H NMR (400 MHz,
Synthesis of glycosyl thiazoles 6a–j; general procedure
DMSO-d6) δ 8.43 (d, J = 9.2 Hz, 1H, NH), 8.05 (d, J = 8.9 Hz, 1H,
NH), 7.86 (d, J = 8.7 Hz, 2H, ArH), 7.44 (d, J = 8.6 Hz, 2H, ArH),
7.28 (s, 1H, Thiazole), 5.30 (t, J = 9.5 Hz, 1H, H-1), 5.21 (t, J = 9.8 Hz,
1H, H-3), 4.86 (t, J = 9.8 Hz, 1H, H4), 4.19 (dd, J = 12.4, 4.8 Hz, 1H,
H-6), 4.01–3.89 (m, 3H, H-2, H-5, H-6’), 1.99–1.76 (m, 12H, 4 × CH3);
HRMS (ESI) m/z calcd for: C23H26ClN3NaO8S [M + Na]+ 562.1021;
found: 562.1032.
Copper(II) bromide (0.5 g, 2.2 mmol) was added to a solution of 4
(1 mmol) in EtOAc (15 mL) and CHCl3 (15 mL). The reaction mixture
was stirred and monitored by TLC. After completion of reaction, the
mixture was filtrated and the solvent was washed by water until it was
colourless. The solvent was eliminated under reduced pressure to give
5. Without any purification, 5 was added to a solution of 3 (1 mmol) in
EtOH (25 mL). The mixture was completed in 0.5 h under refluxing
followed by the elimination of EtOH. The crude product was added to
Et2O and sonicated. Filtration of the mixture afforded the pure desired
compounds 6a–j.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(4-bromophenyl)-1,3-thiazole-2-amine (6g): Yellow solid; yield
0.501 g (86%); m.p. 127–128 °C; IR (nmax/cm–1) KBr: 3347, 2947, 1747,
1
1656, 1547, 1472, 1232, 1039, 907; H NMR (400 MHz, DMSO-d6) δ
8.43 (d, J = 9.2 Hz, 1H, NH), 8.05 (d, J = 8.9 Hz, 1H, NH), 7.79 (d,
J = 8.5 Hz, 2H, ArH), 7.58 (d, J = 8.6 Hz, 2H, ArH), 7.29 (s, 1H,
Thiazole), 5.30 (t, J = 9.4 Hz, 1H, H-1), 5.21 (t, J = 9.8 Hz, 1H, H-3),
4.84 (t, J = 9.7 Hz, 1H, H-4), 4.19 (dd, J = 12.4, 4.8 Hz, 1H, H-6),
4.00–3.89 (m, 3H, H-2, H-5, H-6’), 1.99–1.75 (m, 12H, 4 × CH3);
HRMS (ESI) m/z calcd for: C23H26BrN3NaO8S [M + Na]+ 606.0516;
found: 606.0514.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(4-nitrophenyl)-1,3-thiazole-2-amine (6h): Yellow solid; yield
0.457 g (83%); m.p. 225–226 °C; IR (nmax/cm–1) KBr: 3421, 2929, 1744,
1656, 1601, 1529, 1232, 1038, 912; 1H NMR (400 MHz, DMSO-d6)
δ 8.74 (d, J = 7.5 Hz, 1H, NH), 8.26 (d, J = 8.8 Hz, 2H, ArH), 8.10
(d, J = 8.8 Hz, 2H, ArH), 7.83 (d, J = 8.9 Hz, 1H, NH), 7.67 (s, 1H,
Thiazole), 5.56 (t, J = 9.7 Hz, 1H, H-1), 5.43 (t, J = 9.5 Hz, 1H, H-3),
4.93 (t, J = 9.8 Hz, 1H, H-4), 4.31 (d, J = 17.1, 8.3 Hz, 1H, H-6),
4.20–3.94 (m, 3H, H-2, H-5, H-6’), 1.98–1.81 (m, 12H, 4 × CH3).
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-phenyl-1,3-thiazole-2-amine (6a): Pale yellow solid; yield 0.465 g
(92%); m.p. 98–100 °C; IR (nmax/cm–1) KBr: 3379, 2926, 1747, 1666,
1
1547, 1444, 1233, 1040, 917; H NMR (400 MHz, DMSO-d6) δ 8.40
(d, J = 9.3 Hz, 1H, NH), 8.06 (d, J = 8.9 Hz, 1H, NH), 7.85 (m, 2H,
ArH), 7.38 (t, J = 7.6 Hz, 2H, ArH), 7.28 (t, J = 7.3 Hz, 1H, ArH), 7.22
(s, 1H, Thiazole), 5.30 (t, J = 9.5 Hz, 1H, H-1), 5.22 (t, J = 9.8 Hz,
1H, H-3), 4.86 (t, J = 9.7 Hz, 1H, H-4), 4.19 (dd, J = 12.3, 4.9 Hz, 1H,
H-6), 4.01–3.89 (m, 3H, H-2, H-5, H-6’), 1.99–1.75 (m, 12H, 4 × CH3);
HRMS (ESI) m/z calcd for: C23H27N3NaO8S [M + Na]+ 528.1411;
found: 528.1423.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(4-methylphenyl)-1,3-thiazole-2-amine (6b): Pale yellow solid;
yield 0.483 g (93%); m.p. 95–96 °C; IR (nmax/cm–1) KBr: 3370,
1
2930, 1748, 1668, 1549, 1437, 1234, 1039, 911; H NMR (400 MHz,
DMSO-d6) δ 8.35 (d, J = 9.3 Hz, 1H, NH), 8.05 (d, J = 8.9 Hz, 1H,

548 JOURNAL OF CHEMICAL RESEARCH 2016
HRMS (ESI) m/z calcd for: C23H26KN4O10S [M + K]+ 589.1001; found:
589.1000.
Science and Technology Research Funds Projects of Ocean
(201505023).
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-
4-(3-nitrophenyl)-1,3-thiazole-2-amine (6i): Yellow solid; yield
0.446 g (81%); m.p. 101–102 °C; IR (nmax/cm–1) KBr: 3391, 2928, 1748,
1658, 1543, 1436, 1231, 1040, 907; 1H NMR (400 MHz, DMSO-d6) δ
8.64 (m, 1H, ArH), 8.57 (d, J = 9.3 Hz, 1H, NH), 8.30 (d, J = 7.7 Hz,
1H, ArH), 8.14 (d, J = 8.2, 2.3 Hz, 1H, ArH), 8.06 (d, J = 9.0 Hz, 1H,
NH), 7.69 (d, J = 8.8 Hz, 1H, ArH), 7.56 (s, 1H, Thiazole), 5.32 (t,
J = 9.4 Hz, 1H, H-1), 5.23 (t, J = 9.8 Hz, 1H, H-3), 4.87 (t, J = 9.8 Hz,
1H, H-4), 4.19 (dd, J = 12.4, 4.7 Hz, 1H, H-6), 4.01–3.91 (m, 3H, H-2,
H-5, H-6’), 1.99–1.75 (m, 12H, 4 × CH3). HRMS (ESI) m/z calcd for:
C23H26KN4O10S [M + K]+ 589.1001; found: 589.1003.
N-(2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)
biphenyl-4-yl-1,3-thiazole-2-amine (6j): White solid; yield 0.511 g
(88%); m.p. 215–216 °C; IR (nmax/cm–1) KBr: 3406, 2926, 1745, 1658,
1549, 1479, 1227, 1043, 916;1H NMR (400 MHz, DMSO-d6) δ 8.42 (d,
J = 9.3 Hz, 1H, NH), 8.07 (d, J = 9.1 Hz, 1H, NH), 7.93 (dd, J = 8.4,
4.6 Hz, 2H, ArH), 7.70 (m, 3H, ArH), 7.48 (t, J = 7.7 Hz, 2H, ArH),
7.36 (dd, J = 13.6, 6.2 Hz, 2H, ArH), 7.28 (s, 1H, Thiazole), 5.32 (t,
J = 9.5 Hz, 1H, H-1), 5.23 (t, J = 9.7 Hz, 1H, H-3), 4.87 (t, J = 9.7 Hz,
1H, H-4), 4.21 (dd, J = 12.3, 4.6 Hz, 1H, H-6), 4.02–3.91 (m, 3H, H-2,
H-5, H-6’), 1.99–1.76 (m, 12H, 4 × CH3); HRMS (ESI) m/z calcd for:
C29H31N3NaO8S [M + Na]+ 604.1724; found: 604.1724.
Received 9 April 2016; accepted 27 June 2016
Paper 1604042 doi: 10.3184/174751916X14711768865726
Published online: 26 August 2016
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Product 7a was selected as an example
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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
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