Synthesis and bioactivity of 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N- xylopyranosyl-1,3,4-oxa(thia)diazol-2-amines

Article abstract of DOI:10.1016/j.carres.2011.01.010

A series of new N′-[N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl) thiocarbamoyl]-2-[(1-aryl-1H-tetrazol-5-yl)sulfanyl]acetohydrazides 5a-5e were synthesized rapidly in high yields from 2-(1-aryl-1H-tetrazol-5-ylsulfanyl) acetohydrazides 3a-3e and 2,3,4-tri-O-a

Full text of DOI:10.1016/j.carres.2011.01.010

Carbohydrate Research 346 (2011) 551–559
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis and bioactivity of 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-
N-xylopyranosyl-1,3,4-oxa(thia)diazol-2-amines
Yao-Wu He a,b,d, Ling-Hua Cao a,b, , Jian-Bin Zhang c, Duo-Zhi Wang b, Haji Akber Aisa a,
⇑
⇑
a Key Laboratory of Chemistry of Plant Resources in Arid Regions, Chinese Academy of Sciences, Xinjiang Technical Institute of Physics and Chemistry, Urumqi 830011, PR China
b College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046, PR China
c Physics and Chemistry Test Center of Xinjiang University, Urumqi 830046, PR China
d Graduate University of the Chinese Academy of Sciences, Beijing 100049, PR China
a r t i c l e i n f o
a b s t r a c t
A series of new N0-[N-(2,3,4-tri-O-acetyl-b-
D-xylopyranosyl)thiocarbamoyl]-2-[(1-aryl-1H-tetrazol-5-yl)
Article history:
Received 1 May 2010
Received in revised form 10 January 2011
Accepted 11 January 2011
Available online 15 January 2011
sulfanyl]acetohydrazides 5a–5e were synthesized rapidly in high yields from 2-(1-aryl-1H-tetrazol-5-
ylsulfanyl)acetohydrazides 3a–3e and 2,3,4-tri-O-acetyl-b- -xylopyranosyl isothiocyanate 4, then
5a–5e were converted to a series of new 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-
acetyl-b- -xylopyranosyl)-1,3,4-oxadiazole-2-amines 6a–6e and 5-(1-aryl-1H-tetrazol-5-ylsulfanylm-
ethyl)-N-(2,3,4-tri-O-acetyl-b- -xylopyranosyl)-1,3,4-thiadiazole-2-amines 7a–7e, respectively under
D
D
D
Keywords:
Aryltetrazole
Xylopyranosyl isothiocyanate
Oxadiazole
Thiadiazole
mercuric acetate/alcohol system or acetic anhydride/phosphoric acid system, then deacetylated in the
solution of CH3ONa/CH3OH. All of the novel compounds were characterized by IR, 1H NMR, 13C NMR,
MS and elemental analysis. The structures of compounds 2e, 3e, 5a and 5c have been determined by
X-ray diffraction analysis. Some of the synthesized compounds displayed PTP1B inhibition and microor-
ganism inhibition.
Crystal structure
Biological activity
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
Protein tyrosine phosphatase 1B (PTP1B) is a very important
protein tyrosine phosphatase that has been implicated in the reg-
Most heterocycles have a wide application as drugs in the phar-
maceutical industry, as dyes or in agriculture. Tetrazoles, being an
important class of heterocyclic compounds, can be used not only as
precursors to a variety of nitrogen-containing heterocycles but also
as materials with applications in diverse areas such as pharmaceu-
ticals, explosives, information recording systems, and corrosion
inhibitors.1–3 1,3,4-Oxadiazole compounds represent one of the
most active classes of compounds possessing broad spectrum of
biological activities as antibacterial, anti-fungal, analgesic, anti-
inflammatory, anti-hypertension and muscle-relaxing activities.4,5
A large number of 1,3,4-thiadiazoles have been applied in the agri-
cultural field as herbicides,6 fungicides7 and bactericides.8 In the
medical field, one of the best known drugs based on a 1,3,4-thiadi-
azole is acetazolamide (acetazola),9 a carbonic anhydrase inhibitor
launched in 2003.10 The lead compounds modified by saccharides
and their derivatives can decrease the toxicity and side effect effi-
ciently. They can also enhance the pharmaceutical effect. There-
fore, it is a promising research project to modify lead compounds
by saccharides.11 Xylose is a non-caloric sweetener, used for diabe-
tes and obesity.
ulation of insulin action and in other signal transduction path-
ways.12 The study indicates that protein tyrosine phosphatase 1B
is a novel target for the treatment of diabetes and obesity. Inhibi-
tion of PTP1B’s activity could improve the sensitivity of insulin sig-
naling. To seek highly effective inhibitors of PTP1B has a promising
application in diabetes and obesity therapy.
In the recent years, we had reported that various glycosyl iso-
thiocyanates exhibited a high reactivity to the synthesis of carbo-
hydrates and their derivatives.13–28 Our intention was therefore
to realize reinforcement of physiological activities by means of
combining xylosyl and aryltetrazole with 1,3,4-oxadiazoles or
1,3,4-thiadiazoles. The synthetic route was shown in Scheme 1.
2. Results and discussion
2.1. Chemistry
In the process of the synthesis of N0-[N-(2,3,4-tri-O-acetyl-b-
D-
xylopyranosyl)thiocarbamoyl]-2-(1-aryl-1H-tetrazol-5-ylsulfanyl)
acetohydrazides (5a–5e), anhydrous benzene was used as
solvent to avoid the hydrolysis of 2,3,4-tri-O-acetyl-b-D-xylopyr-
anosyl isothiocyanate (4). The appropriate molar ratio of hydrazine
hydrate with ethyl 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)acetates
(2a–2e) for the synthesis of 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)
⇑
Corresponding authors.
E-mail addresses: clhxj@xju.edu.cn (L.-H. Cao), haji@ms.xjb.ac.cn (H.A. Aisa).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.01.010

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Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
N
N
N
N
N
N
N
N
N
SH
SCH2CO2C2H5
SCH2CONHNH2
3a 3e
N2H4 H2O
ClCH2CO2C2H5
NaOH
N
N
N
Ar
1a 1e
~
Ar
~
Ar
2a~2e
O
S
AcO
N
N
N
3
2
N
N
O
1
OAc
OAc
AcO
benzene
SCH2CONHNH2
+
SCH2CNHNHCNH
NCS
N
O
AcO
5
N
N
4
OAc
Ar
Ar
3a~3e
4
5a~5e
N
N
AcO
O
N
N
Hg(OAc)2
C2H5OH
N
N
SCH2
NH
OAc
OAc
O
6a~6e
Ar
5
AcO
O
N
N
N
N
N
H3PO4
Ac2O
SCH2
NH
N
OAc
OAc
S
N
7a 7e
~
Ar
N
HO
N
MeOH/MeONa
MeOH/MeONa
N
N
6a 6e
~
SCH2
NH
NH
OH
OH
O
O
N
8a~8e
Ar
HO
O
N
N
N
N
N
7a 7e
~
SCH2
OH
OH
S
N
9a 9e
~
Ar
Ar a :Ph; b: p-CH3C6H4; c: p-ClC6H4; d: p-CH3OC6H4; e: o-CH3C6H4
Scheme 1.
acetohydrazides (3a–3e) was 5:1. Then the yield was improved
and the products were purified easily.
2.2. Crystal structures
The 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-
To further understand the important effect of structural factors
on their interactions, the crystal structure of compounds 2e, 3e, 5a
and 5c were investigated. Transparent colorless crystals were ob-
tained by slow evaporation from ethanol solution over several days.
So far, attempts to obtain single crystals of 6a–6e, 7a–7e, 8a–8e and
9a–9e have been unsuccessful. The molecular structures of 2e, 3e, 5a
and 5c are shown in Figures1–4, respectively. Compound 2e belongs
to monoclinic system with space P2 (1)/c and unit cell parameters:
a = 7.5908(15) Å, b = 17.547(4) Å, c = 10.757(2) Å, b = 103.48(3)°,
acetyl-b-
D-xylopyranosyl)-1,3,4-oxadiazole-2-amines
(6a–6e)
were prepared by cyclization of the intermediate of compounds
5a–5e with mercury acetate in high yield. The 5-(1-aryl-1H-tetra-
zol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-
1,3,4-thiadiazole-2-amines (7a–7e) were obtained in high yield by
the treatment compounds 5a–5e with Ac2O and phosphoric acid.
The structures of the compounds were established and con-
firmed on the basis of their elemental analyses and spectral data.
The IR spectra of compounds 5a–5e exhibited strong bands at
about 1540 cmꢀ1 which was attributed to characteristic absorption
of NH–CS–NH. However, as to the target compounds 6a–6e and
7a–7e, the characteristic absorption of NH–CS–NH disappeared.
These phenomena suggested the existence of the oxadiazole/thia-
diazole. The signals at about 1745 cmꢀ1 showed the absorption
feature of C@O in the acetyl of sugar ring. However, in the target
compounds 8a–8e and 9a–9e, the characteristic absorption of
C@O disappeared, and the strong bands appeared at about
3300 cmꢀ1 which was attributed to characteristic absorption of
N–H and O–H. These indicated that the acetyl in the sugar ring
had been removed. The medium band at about 910 cmꢀ1 was the
characteristic absorption of C1–H in the sugar ring, which indi-
cated that all the compounds were b-anomer.
Z = 4, D = 1.260 mg/m3,
l
= 0.234 mmꢀ1, F(0 0 0) = 528. Compound
3e belongs to monoclinic system with space P2 (1)/c and unit cell
parameters: a = 17.640(4) Å, b = 8.9326(18) Å, c = 7.8119(16) Å,
b = 90.46(3)°, Z = 4, D = 1.361 mg/m3,
l
= 0.259 mmꢀ1, F(0 0 0) =
504. Compound 5e belongs to Orthorhombic system with space
P2(1)2(1)2(1) and unit cell parameters: a = 9.5924(19) Å, b =
12.641(3) Å, c = 23.292(5) Å, b = 103.48(3)°, Z = 4, D = 1.335
mg/m3,
l
= 0.243 mmꢀ1, F(0 0 0) = 1184. Compound 5c belongs to
Monoclinic system with space P2(1) and unit cell parameters:
a = 9.7023(19) Å, b = 12.800(3) Å, c = 11.889(2) Å, b = 99.36(3)°,
Z = 2, D = 1.407 mg/m3,
l
= 0.331 mmꢀ1, F(0 0 0) = 642.
2.3. Biological activities
In the 1H NMR spectra of compounds 6a–6e and 7a–7e, three
single peaks appearing at about d 2.00 were attributed to hydrogen
atoms of acetyl in the sugar ring; while multiple peaks appearing
at about d 3.40–5.30 were attributed to hydrogen atoms of the su-
gar ring. Additionally, the signals of the sugar ring C1–H displayed
at about d 5.30 and revealed a triplet-peak for coupling with C2–H
and N–H.
Compounds 6a–6e, 7a–7e, 8a–8e and 9a–9e were evaluated in
inhibition of PTP1B. The NaVO3 was used as a reference of positive
drug. The IC50 of NaVO3 is 10 lmol/L. The bioassay results showed
that compounds 6a, 6b, 6c, 6e, 8a and 8e had a very potent PTP1B
inhibition activity. Compounds 6a–6e, 7a–7e, 8a–8e and 9a–9e
were also tested for inhibition of microorganism include Staphylo-
coccus aureus, Colibacillus and Candida albicans. The bioassay results

Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
553
Figure 1. X-ray crystallographic structure of compound 2e.
Figure 2. X-ray crystallographic structure of compound 3e.
Figure 3. X-ray crystallographic structure of compound 5a.

554
Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
Inova-600 (using TMS as internal standard). Chemical shifts are
expressed as d units, using CDCl3, DMSO-d6 or CD3OD as solvent.
The IR spectra were recorded as KBr pellets on a Bruker FT-IR Equi-
nox 55 instrument. ESI-MS data were obtained in an HP 1100 LC/
MS instrument. Elemental analyses were performed on a Thermo
Flash EA-1112 analyzer. The crystal structure of compounds was
determined on an R-AXIS SPIDER X-ray diffractometer. Analytical
thin-layer chromatography (TLC) was performed on silica gel
GF254 (Qingdao, China) and 0.5% CMC, and detected by UV light
or iodine vapor. Column chromatography was performed on silica
gel (100–200 mesh). All reagents were commercial products of
analytical grade and were used directly without processing unless
noted otherwise. The boiling point range of petroleum ether was
60–90 °C.
3.2. Compounds 1a–1e were prepared by the published
procedure29
Figure 4. X-ray crystallographic structure of compound 5c.
Compound 1a: White solid, yield 90%; mp 162–164 °C (lit.29
yield 96%, mp 155–156 °C).
showed that compounds 6a, 6b, 6c, 6e, 8a, 8c, 8e and 9e had a
rather S. aureus inhibition activity, and compounds 6b, 6c, 6e and
8e had some Colibacillus inhibition activity, but no compounds dis-
played significantly C. albicans inhibition activity. The activity re-
sults were shown in Table 1. These results revealed that the
synthesized oxadiazole derivatives had higher inhibition activity
than thiadiazole derivatives, and the acetylated compounds had
better inhibition activity than the deacetylated compounds. The
Compound 1b: White solid, yield 89%; mp 166–168 °C.
Compound 1c: White solid, yield 90%; mp 178–180 °C.
Compound 1d: White solid, yield 87%; mp 172–173 °C.
Compound 1e: White solid, yield 90%; mp 139–141 °C.
3.3. Preparation of ethyl 2-(1-aryl-1H-tetrazol-5-ylsulfanyl)
acetates 2a–2e in terms of the literature10
a
1B adrenergic receptor agonist activity of 6d and 7d was tested,
but they did not show significant activity.
Compounds 2a–2e were prepared according to the literature
while using ethyl chloroacetate replaces methyl chloroacetate as
a material.
3. Experimental
Compound 2a: White solid, yield 72%, mp 79–80 °C.
Compound 2b: White solid, yield 61%, mp73–74.5 °C.
Compound 2c: White solid, yield 65%, mp 74–77 °C.
Compound 2d: White solid, yield 62%, mp 61–62 °C.
Compound 2e: White solid, yield 70%, mp 77–78 °C.
3.1. General methods
Melting points were determined on a Yanaco MP-S3 micro
melting point apparatus and are corrected. The 1H NMR and 13C
NMR spectra were recorded on a Varian Inova-400 or Varian
3.4. Preparation of compounds 2-(1-aryl-1H-tetrazol-5-
ylsulfanyl)acetohydrazides 3a–3e
Table 1
Activity results of tested compounds
A solution of 1 mmol compounds 2a–2e and 5 mmol hydrazine
hydrate in 10 mL of ethanol was stirred and refluxed for about 4 h.
The solvent was removed to give a residue that was recrystallized
from ethanol.
Compd
PTP1B* inhibition
Microorganism inhibition
IC50
mol/L)
Staphylococcus aureus
Colibacillus
Candida albicans
(
l
Compound 3a: White solid, yield 80%, mp 161–163 °C (lit.29 mp
158–159 °C).
6a
6b
6c
6d
6e
7a
7b
7c
12.64
2.76
3.98
—
15.71
—
++ꢁ+++
—
+
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
++ꢁ+++
Compound 3b: White solid, yield 76%, mp 181–183 °C.
Compound 3c: White solid, yield 70%, mp 175–176 °C.
Compound 3d: White solid, yield 81%, mp178–179.5 °C.
Compound 3e: White solid, yield 78%, mp 102–104 °C.
++ꢁ+++
ꢁ+
—
ꢁ+
—
—
—
—
—
ꢁ+
—
—
—
—
—
—
—
—
—
—
++
—
—
220.54
—
—
3.5. 2,3,4-Tri-O-acetyl-xylopyranosyl isothiocyanate 4 was
7d
7e
193.09
—
—
—
prepared by the published procedure30
8a
8b
8c
8d
8e
9a
9b
9c
9d
9e
28.06
117.25
111.01
539.68
18.54
70.34
—
166.85
227.43
94.46
10
+
—
+
—
3.5.1. 2,3,4-Tri-O-acetyl-xylopyranosyl isothiocyanate 4
Yield 40%, mp 85–86 °C (lit.30 yield 41%, mp 88–90 °C).
+ꢁ++
3.6. General procedure for the preparation of N0-[N-(2,3,4-tri-O-
acetyl-b-D-xylopyranosyl)thiocarbamoyl]-2-(1-aryl-1H-tetrazol-
5-ylsulfanyl)acetohydrazides 5a–5e
—
—
—
—
+ꢁ++
NaVO3
An equimolecular mixture of 4 (5 mmol) and 3a–3e (5 mmol) in
20 mL of dry benzene was heated under reflux about 4 h. After the
reaction was completed (TLC, expended matter: EtOAc–petroleum
ether 3:1, v/v), the mixture was concentrated. The pure production
was obtained by recrystallization from ethanol.
ꢁ+: Diameter of antibacterial circle <4 mm; +: diameter of antibacterial circle
4–5 mm; ++: diameter of antibacterial circle 5–7 mm; +++: diameter of antibacte-
rial circle 7–9 mm; ++++: diameter of antibacterial circle P10 mm.
a
PTP1B: Protein tyrosine phosphatase 1B; IC50: 50% inhibiting concentration.

Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
555
3.6.1. N0-[N-(2,3,4-Tri-O-acetyl-b-
2-(1-phenyl-1H-tetrazol-5-ylsulfanyl)acetohydrazide (5a)
D-xylopyranosyl)thiocarbamoyl]-
(DMSO-d6, 150 MHz): d 171.84, 170.48, 169.97, 163.29 (C@O),
158.72 (C@N), 135.51, 128.57, 118.63 (phenyl–C), 80.27 (C1),
68.81 (C3), 68.45 (C5), 65.18 (C4), 28.69, 22.80, 22.56, 21.37
White solid, yield 75%, mp 178–180 °C; 1H NMR (DMSO-d6,
600 MHz): d 2.03, 2.05, 2.06 (3s, 9H, CH3CO), 3.41 (t, J = 11 Hz,
1H, C4–H), 3.87 (dd, J = 11.1, 5.6 Hz, 1H, C5–Ha), 4.10 (d,
J = 15.6 Hz, 1H, SCHa), 4.15 (d, J = 15.6 Hz, 1H, SCHb), 4.76 (m, 1H,
C5–Hb), 4.97 (t, J = 9.3 Hz, 1H, C2–H), 5.29 (t, J = 9.6 Hz, 1H, C3–
H), 5.53 (t, J = 9.3 Hz, 1H, C1–H), 7.62–7.71 (m, 5H, ArH); 8.16 (d,
J = 9.1 Hz, 1H, NH), 10.01 (s, 1H, NH), 10.54 (s, 1H, NH); 13C NMR
(DMSO-d6, 150 MHz): d 184.75 (C@S), 172.13, 171.86, 170.23,
167.83 (C@O), 166.56 (C@N), 157.24, 138.14, 134.56 (Phenyl-C),
86.17 (C1), 75.41 (C3), 68.79 (C5), 54.26 (C4), 43.35 (C2), 27.18,
(CH3); IR (KBr)
m: 3335, 3240 (N–H), 1744 (C@O), 1503, 1469,
1394 (C@N, Aryl), 1551 (NH–CS–NH), 1231 (N–N@C), 1062 (C–
O–C) cmꢀ1; ESIMS: m/z (%) 620 (21, [M+23]+), 598 (38, [M+H]+).
Anal. Calcd for C22H27N7O9S2: C, 44.21; H, 4.55; N, 16.41. Found:
C, 44.34; H, 4.53; N, 16.47.
3.6.5. N0-[N-(2,3,4-Tri-O-acetyl-b-
D-xylopyranosyl)thiocarbamoyl]-
2-[1-(2-methylphenyl)-1H-tetrazol-5-ylsulfanyl]acetohydrazide
(5e)
20.96, 19.67 (CH3); IR (KBr)
m
: 3327, 3220 (N–H), 1742 (C@O),
White bulk crystals, yield 67%, mp 193–195 °C; 1H NMR
(DMSO-d6, 600 MHz): d 1.94, 2.00, 2.05 (3s, 9H, CH3CO), 3.48
(t, J = 11.1 Hz, 1H, C4–H), 3.92 (dd, J = 11.4, 5.4 Hz, 1H, C5–Ha),
4.11 (d, J = 15.6 Hz, 1H, SCHa), 4.17 (d, J = 15.6 Hz, 1H, SCHb),
4.81–4.84 (m, 1H, C5–Hb), 5.00 (t, J = 9.3 Hz, 1H, C2–H), 5.25
(t, J = 9.6 Hz, 1H, C3–H), 5.76 (t, J = 9.3 Hz, 1H, C1–H), 7.47–
7.62 (m, 4H, ArH); 8.27 (d, J = 9.6 Hz, 1H, NH), 9.93 (s, 1H,
1502 (C@N, Aryl), 1535 (NH–CS–NH), 1234 (N–N@C), 1039 (C–O–
C) cmꢀ1; ESIMS: m/z (%) 590 (15, [M+23]+), 568 (32, [M+H]+). Anal.
Calcd for C21H25N7O8S2: C, 44.44; H, 4.44; N, 17.27. Found: C,
44.52; H, 4.42; N, 17.32.
3.6.2. N0-[N-(2,3,4-Tri-O-acetyl-b-
D-xylopyranosyl)
thiocarbamoyl]-2-[1-(4-methylphenyl)-1H-tetrazol-5-
NH), 10.39 (s, 1H, NH); 13C NMR (DMSO-d6, 150 MHz):
d
ylsulfanyl]acetohydrazide (5b)
183.67 (C@S), 170.29, 170.21, 169.87, 166.56 (C@O), 155.93
(C@N), 135.60, 132.41, 132.25, 128.22, 127.78, 127.69 (Phenyl-
C), 83.08 (C1), 73.19 (C3), 71.07 (C5), 69.15(C4), 64.16 (C2),
White solid, yield 73%, mp 188.5–190 °C; 1H NMR (CDCl3,
600 MHz): d 1.99, 2.01, 2.04 (3s, 9H, CH3CO), 2.53 (s, 3H, CH3),
3.46 (t, J = 11.1 Hz, 1H, C4–H), 3.91 (dd, J = 11.4, 5.4 Hz, 1H, C5–
Ha), 4.79 (s, 2H, SCH2), 4.85 (m, 1H, C5–Hb), 4.93 (t, J = 9.0 Hz,
1H, C2–H), 5.22 (t, J = 9.6 Hz, 1H, C3–H), 5.41 (t, J = 9.0 Hz, 1H,
C1–H), 7.27–7.36 (m, 4H, ArH), 8.37 (d, J = 9.8 Hz, 1H, NH), 9.75
(s, 1H, NH), 10.22 (s, 1H, NH); 13C NMR (CDCl3, 150 MHz): d
181.25 (C@S), 171.58, 170.24, 160.31, 159.56 (C@O), 155.43
(C@N), 136.78, 120.18, 117.85 (Phenyl-C), 82.14 (C1), 60.17 (C3),
42.55 (C5), 35.41 (C4), 25.78, 23.44, 21.09, 19.97 (CH3); IR (KBr)
35.19 (SCH2), 21.16, 21.05, 20.98, 17.39 (CH3); IR (KBr)
m:
3339, 3245 (N–H), 1746 (C@O), 1508, 1447, (C@N, Aryl), 1546
(NH–CS–NH), 1235 (N–N@C), 1083 (C–O–C) cmꢀ1; ESIMS: m/z
(%) 604 (20, [M+23]+), 582 (35, [M+H]+). Anal. Calcd for
C22H27N7O8S2: C, 45.43; H, 4.68; N, 16.86. Found: C, 45.53; H,
4.66; N, 16.93.
3.7. General procedure for the preparation of 5-(1-aryl-1H-
m
: 3321, 3235 (N–H), 1740 (C@O), 1634, 1596, 1499 (C@N, Aryl),
tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-b-D-
xylopyranosyl)-1,3,4-oxadiazole-2-amines 6a–6e
1560 (NH–CS–NH), 1221 (N–N@C), 1060 (C–O–C) cmꢀ1; ESIMS:
m/z (%) 604 (16, [M+23]+), 582 (30, [M+H]+). Anal. Calcd for
C
22H27N7O8S2: C, 45.43; H, 4.68; N, 16.86. Found: C, 45.50; H,
The Hg(OAc)2 (0.6 mmol) was added to a solution of the corre-
sponding compounds 5a–5e (0.5 mmol) in EtOH (20 mL), then the
reaction mixture was stirred and refluxed for 3–4 h until TLC
(EtOAc/petroleum ether, 3:1, v/v) revealed complete consumption
of the starting material. EtOAc (20 mL) was added to the reaction
mixture. The precipitate was filtered off and the filtrate was con-
centrated. The pure production was obtained by recrystallization
from ethanol.
4.70; N, 16.91.
3.6.3. N0-[N-(2,3,4-Tri-O-acetyl-b-
D-xylopyranosyl)thiocarbamoyl]-
2-[1-(4-chlorophenyl)-1H-tetrazol-5-ylsulfanyl]acetohydrazide
(5c)
White solid, yield 79%, mp 199–201 °C; 1H NMR (DMSO-d6,
600 MHz): d 1.88, 1.94, 1.99 (3s, 9H, CH3CO), 3.48 (t, J = 10.8 Hz,
1H, C4–H), 3.93 (dd, J = 11.1, 5.1 Hz, 1H, C5–Ha), 4.12 (d,
J = 15.6 Hz, 1H, SCHa), 4.17 (d, J = 15.6 Hz, 1H, SCHb), 4.81–4.85 (m,
1H, C5–Hb), 4.95 (t, J = 9.3 Hz, 1H, C2–H), 5.25 (t, J = 9.6 Hz, 1H,
C3–H), 5.76 (t, J = 9.3 Hz, 1H, C1–H), 7.74–7.79 (m, 4H, ArH); 8.23
(d, J = 9 Hz, 1H, NH), 9.94 (s, 1H, NH), 10.40 (s, 1H, NH); 13C NMR
(DMSO-d6, 150 MHz): d 183.66 (C@S), 170.27, 170.18, 169.91,
166.56 (C@O), 155.01 (C@N), 136.04, 132.49, 130.83, 127.09 (phe-
nyl-C), 83.08 (C1), 73.21 (C3), 71.05 (C5), 69.17 (C4), 64.17 (C2),
3.7.1. 5-(1-Phenyl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-
O-acetyl-b-
White solid, yield 51%, mp 202.5–203.5 °C; 1H NMR (CDCl3,
400 MHz): 2.03. 2.04, 2.06 (3s, 9H, CH3CO), 3.36 (t, 1H,
D-xylopyranosyl)-1,3,4-oxadiazole-2-amine (6a)
d
J = 10.8 Hz, C4–H), 4.21 (dd, J = 11.1, 5.2 Hz, 1H, C5–Ha), 4.71 (s,
2H, SCH2), 4.91–4.96 (m, 2H, C5–Hb, C2–H), 4.98–5.02 (m, 1H,
C3–H), 5.24–5.31 (m, 1H, C1–H), 5.74 (br 1H, NH), 7.58 (s, 5H,
35.69 (SCH2), 21.16, 21.06, 20.99 (CH3); IR (KBr)
m
: 3335, 3237 (N–
ArH); 13C NMR (CDCl3, 150 MHz):
d 175.57, 170.93, 169.21
H), 1737 (C@O), 1496, 1473 (C@N, Aryl), 1553 (NH–CS–NH), 1239
(N–N@C), 1059 (C–O–C) cmꢀ1; ESIMS: m/z (%) 624 (17, [M+23]+),
602 (37, [M+H]+). Anal. Calcd for C21H24ClN7O8S2: C, 41.89; H, 4.02;
N, 16.29. Found: C, 41.92; H, 4.04; N, 16.24.
(C@O), 160.43, 155.73, 147.22 (C@N), 136.58, 127.34, 119.39 (phe-
nyl-C), 80.00 (C1), 78.19 (C5), 67.69 (C3), 67.18 (C4), 59.74 (C2),
38.14 (SCH2), 23.86, 21.44, 19.57 (CH3); IR (KBr) m: 3182 (N–H),
1740 (C@O), 1629, 1585, 1500 (C@N Aryl), 1264 (N–N@C), 1040
(C–O–C), 910 (C1–H) cmꢀ1; ESIMS: m/z (%) 556 (23, [M+23]+),
534 (33, [M+H]+). Anal. Calcd for C21H23N7O8S: C, 47.28; H, 4.35;
N, 18.38. Found: C, 47.36; H, 4.33; N, 18.34.
3.6.4. N0-[N-(2,3,4-Tri-O-acetyl-b-
D-xylopyranosyl)thiocarbamoyl]-
2-[1-(4-methoxyphenyl)-1H-tetrazol-5-ylsulfanyl]acetohydrazide
(5d)
White solid, yield 80%, mp 203–205 °C; 1H NMR (DMSO-d6,
600 MHz): d 1.97, 1.99, 2.04 (3s, 9H, CH3CO), 3.73 (s, 3H, OCH3),
3.38 (t, J = 11.1 Hz, 1H, C4–H), 3.84 (dd, J = 11.7, 5.4 Hz, 1H, C5–
Ha), 4.91 (s, 2H, SCH2), 4.92–4.97 (m, 1H, C5–Hb), 5.00
(t, J = 9.0 Hz, 1H, C2–H), 5.34 (t, J = 9.6 Hz, 1H, C3–H), 5.41
(t, J = 9.0 Hz, 1H, C1–H), 7.13–7.54 (m, 4H, ArH), 8.16 (d,
J = 9.2 Hz, 1H, NH), 9.86 (s, 1H, NH), 10.54 (s, 1H, NH); 13C NMR
3.7.2. 5-[1-(4-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-oxadiazole-2-
amine (6b)
White acicular crystal, yield 57%, mp 198–199 °C; 1H NMR
(CDCl3, 600 MHz): d 2.05, 2.06, 2.07 (3s, 9H, CH3CO), 2.46 (s, 3H,
CH3), 3.45 (t, J = 11 Hz, 1H, C4–H), 4.10 (dd, J = 11.4, 6.0 Hz, 1H,
C5–Ha), 4.71 (s, 2H, SCH2), 4.95–4.96 (m, 2H, C5–Hb, C2–H),

556
Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
4.98–5.03 (m, 1H, C3–H), 5.30–5.34 (m, 1H, C1–H), 5.97 (br, 1H,
NH), 7.26–7.43 (m, 4H, ArH); 13C NMR (CDCl3, 150 MHz): d
178.42, 170.96, 169.83 (C@O), 169.76, 162.14, 156.96 (C@N),
152.31, 145.38, 141.05, 130.54, 123.77, 113.65 (phenyl-C), 81.88
(C1), 70.68 (C5), 68.87 (C3), 64.32 (C4), 51.16 (C2), 36.25 (SCH2),
3.8. General procedure for the preparation of 5-(1-aryl-1H-
tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-O-acetyl-b-D-
xylopyranosyl)-1,3,4-thiadiazole-2-amine 7a–7e
A mixture of 5a–5e (1 mmol), Ac2O (10 mL) and 85% H3PO4
(0.5 mL) was stirred at room temperature for 24 h. EtOAc
(20 mL) was added to the reaction mixture. The mixture was
successively washed with brine, saturated with NaHCO3 solution,
and water, then dried with Na2SO4, and concentrated under re-
duced pressure to afford the yellow syrup. The crude product
was further purified by flash chromatography on a silica gel col-
umn chromatograph (eluent: CHCl3/EtOAc, 5:1, v/v) to obtain
7a–7e.
20.65, 20.61, 19.52 (CH3); IR (KBr)
m: 3186 (N–H), 1739 (C@O),
1635, 1586, 1518 (C@N, Aryl), 1235 (N–N@C), 1038 (C–O–C), 901
(C1–H) cmꢀ1
;
ESIMS: m/z (%) 570 (19, [M+23]+), 548 (31,
[M+H]+). Anal. Calcd for C22H25N7O8S: C, 48.26; H, 4.60; N, 17.91.
Found: C, 48.40; H, 4.58; N, 17.87.
3.7.3. 5-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-oxadiazole-2-
amine (6c)
White solid, yield 62%, mp 200–201 °C; 1H NMR (CDCl3,
600 MHz): d 2.05, 2.06, 2.07 (3s, 9H, CH3CO), 3.44 (t, J = 11 Hz,
1H, C4–H), 4.12 (dd, J = 10.7, 5.4 Hz, 1H, C5–Ha), 4.71 (d,
J = 15.6 Hz, 1H, SCHa), 4.74 (d, J = 15.6 Hz, 1H, SCHb), 4.93 (s,
1H, C5–Hb), 4.95–4.98 (m, 1H, C2–H), 4.99–5.03 (m, 1H, C3-H),
5.31–5.34 (m, 1H, C1–H), 6.06 (br, 1H, NH), 7.27–7.58 (m, 4H,
3.8.1. 5-(1-Phenyl-1H-tetrazol-5-ylsulfanylmethyl)-N-(2,3,4-tri-
O-acetyl-b-D-xylopyranosyl)-1,3,4-thiadiazole-2-amine (7a)
White solid, yield 54%, mp 197–198 °C; 1H NMR (CDCl3,
600 MHz): d 2.06 (1s, 3H, CH3CO), 2.07 (2s, 6H, CH3CO), 3.48 (t,
J = 11.1 Hz, 1H, C4–H), 4.13 (dd, J = 12.0, 5.4 Hz, 1H, C5–Ha), 4.86
(d, J = 15.0 Hz, 1H, SCHa), 4.89 (d, J = 15.0 Hz, 1H, SCHb), 4.96–
4.99 (m, 2H, C5–Hb, C2–H), 5.00–5.04 (m, 1H, C3–H), 5.31–5.36
(m, 1H, C1–H), 6.37 (br, 1H, NH), 7.28–7.60 (m, 5H, ArH); 13C
NMR (CDCl3, 150 MHz): d 170.91, 169.82, 169.78 (C@O), 168.75,
155.89, 153.04 (C@N), 133.35, 130.46, 130.01, 123.65 (phenyl-C),
84.90 (C1), 71.97 (C5), 70.83 (C3), 68.87 (C4), 64.13 (C2), 31.46
ArH); 13C NMR (CDCl3, 150 MHz):
(C@O), 162.12, 156.76, 152.35 (C@N), 136.78, 131.70, 130.32,
125.17, 116.66 (phenyl-C), 83.16 (C1), 71.96 (C5), 70.65 (C3),
68.84 (C4), 64.34 (C2), 26.68 (SCH2), 20.72, 20.68, 20.63 (CH3);
d 171.01, 169.85, 169.78
IR (KBr)
m: 3226 (N–H), 1744 (C@O), 1631, 1585, 1497, 1428
(C@N, Aryl), 1262 (N–N@C), 1040 (C–O–C), 905 (C1–H) cmꢀ1
;
(SCH2), 20.66, 20.63 (CH3); IR (KBr) m: 3222 (N–H), 1740 (C@O),
ESIMS: m/z (%) 590 (28, [M+23]+), 568 (26, [M+H]+). Anal. Calcd
for C21H22ClN7O8S: C, 44.41; H, 3.90; N, 17.26. Found: C, 44.27;
H, 3.91; N, 17.22.
1555, 1511 (C@N, Aryl), 1223 (N–N@C), 1040 (C–O–C), 909 (C1–
H) cmꢀ1; ESIMS: m/z (%) 572 (25, [M+23]+), 550 (18, [M+H]+). Anal.
Calcd for C21H23N7O7S2: C, 45.89; H, 4.22; N, 17.84. Found: C,
45.81; H, 4.24; N, 17.89.
3.7.4. 5-[1-(4-Methoxyphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-oxadiazole-2-
amine (6d)
3.8.2. 5-[1-(4-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-thiadiazole-2-
amine (7b)
White solid, yield 58%, mp 192.5–194 °C; 1H NMR (CDCl3,
600 MHz): d 2.05, 2.06, 2.07 (3s, 9H, CH3CO), 3.45 (t, J = 10.8 Hz,
1H, C4–H), 3.89 (s, 3H, OCH3), 4.10 (dd, J = 10.7, 5.4 Hz, 1H, C5–
Ha), 4.69 (s, 2H, SCH2), 4.96–4.98 (m, 2H, C5–Hb, C2–H), 4.99–
5.03 (m, 1H, C3–H), 5.32 (t, J = 8.7 Hz, 1H, C1–H), 6.06 (br, 1H,
NH), 7.05–7.45 (m, 4H, ArH); 13C NMR (CDCl3, 150 MHz): d
170.92, 169.86, 169.78 (C@O), 162.21, 161.09, 156.92 (C@N),
152.48, 125.85, 125.61, 115.08 (phenyl-C), 83.13 (C1), 70.65(C5),
68.84 (C3), 64.28 (C4), 55.72 (C2), 26.51, 20.70, 20.66, 20.60
White solid, yield 47%, mp 205.5–206.5 °C; 1H NMR (CDCl3,
400 MHz): d 2.03, 2.05, 2.08 (3s, 9H, CH3CO), 2.46 (s, 3H, CH3),
3.53 (t, J = 11 Hz, 1H, C4–H), 4.13 (dd, J = 11.4, 5.4 Hz, 1H, C5–
Ha), 4.82 (s, 2H, SCH2), 4.90–4.92 (m, 2H, C5–Hb, C2–H), 4.97–
5.01 (m, 1H, C3–H), 5.21–5.25 (m, 1H, C1–H), 5.73 (br 1H, NH),
7.38–7.56 (m, 4H, ArH); 13C NMR (CDCl3, 150 MHz): d 172.47,
170.32, 169.83 (C@O), 160.58, 154.57, 147.28 (C@N), 131.54,
120.24, 118.76 (phenyl-C), 82.46 (C1), 73.63 (C5), 70.85 (C3),
69.78 (C4), 51.16 (C2), 33.45 (SCH2), 27.69, 18.73 (CH3); IR
(CH3); IR (KBr)
m: 3221, 3051 (N–H), 1750 (C@O), 1630, 1583,
(KBr)
m: 3235 (N–H), 1741 (C@O), 1515, 1430 (C@N, Aryl),
1514 (C@N, Aryl), 1249 (N–N@C), 1079 (C–O–C), 903 (C1–H)
cmꢀ1; ESIMS: m/z (%) 586 (21, [M+23]+), 564 (36, [M+H]+). Anal.
Calcd for C22H25N7O9S: C, 46.89; H, 4.47; N, 17.40. Found: C,
47.01; H, 4.49; N, 17.45.
1223 (N–N@C), 1040 (C–O–C), 906 (C1–H) cmꢀ1; ESIMS: m/z
(%) 586 (19, [M+23]+), 564 (12, [M+H]+). Anal Calcd for
C22H25N7O7S2: C, 46.88; H, 4.47; N, 17.40. Found: C, 47.03; H,
4.45; N, 17.35.
3.7.5. 5-[1-(2-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
3.8.3. 5-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-oxadiazole-2-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-thiadiazole-2-
amine (6e)
amine (7c)
White solid, yield 54%, mp 207–209 °C; 1H NMR (CDCl3,
400 MHz): d 1.99, 2.03, 2.05 (3s, 9H, CH3CO), 2.30 (s, 3H, CH3),
3.44 (t, J = 11 Hz, 1H, C4–H), 4.10 (dd, J = 11.1, 5.4 Hz, 1H, C5–
Ha), 4.77 (s, 2H, SCH2), 4.93–4.96 (m, 2H, C5–Hb, C2–H), 5.00–
5.04 (m, 1H, C3–H), 5.35–5.43 (m, 1H, C1–H), 5.92 (br, 1H, NH),
7.06–7.48 (m, 4H, ArH); 13C NMR (CDCl3, 150 MHz): d 171.35,
170.81, 169.97 (C@O), 166.36, 155.49 (C@N), 138.12, 135.74,
133.16, 129.27, 117.42 (phenyl-C), 83.52 (C1), 70.86 (C5), 70.51
(C3), 65.17 (C4), 41.2 (C2), 33.69 (SCH2), 26.17, 20.54, 19.37
White solid, yield 38%, mp 208–209 °C; 1H NMR (CDCl3,
600 MHz):
d
1.95, 2.01, 2.10 (3s, 9H, CH3CO), 3.47 (t,
J = 11.1 Hz, 1H, C4–H), 4.13 (dd, J = 11.7, 5.4 Hz, 1H, C5–Ha),
4.85 (d, J = 15 Hz, 1H, SCHa), 4.88 (d, J = 15 Hz, 1H, SCHb), 4.91–
4.96 (m, 2H, C5–Hb, C2–H), 4.98–5.02 (m, 1H, C3–H), 5.23–5.36
(m, 1H, C1–H), 6.46 (br, 1H, NH), 7.26–7.57 (m, 4H, ArH); 13C
NMR (CDCl3, 150 MHz): d 170.91, 169.75, 168.72 (C@O), 155.59,
153.03, 136.67 (C@N), 131.75, 130.31, 124.89 (phenyl-C), 84.84
(C1), 71.82 (C5), 70.73 (C3), 68.79 (C4), 64.11 (C2), 31.52
(CH3); IR (KBr)
m: 3184 (N–H), 1742 (C@O), 1629, 1586, 1498
(SCH2), 20.65 (CH3); IR (KBr) m: 3247 (N–H), 1743 (C@O), 1554,
(C@N, Aryl), 1226 (N–N@C), 1039 (C–O–C), 908 (C1–H) cmꢀ1
;
1495 (C@N, Aryl), 1230 (N–N@C), 1040 (C–O–C), 905 (C1–H)
cmꢀ1; ESIMS: m/z (%) 606 (21, [M+23]+), 584 (8, [M+H]+). Anal
Calcd for C21H22ClN7O7S2: C, 43.19; H, 3.80; N, 16.79. Found: C,
43.23; H, 3.79; N, 16.83.
ESIMS: m/z (%) 570 (24, [M+23]+), 548 (28, [M+H]+). Anal. Calcd
for C22H25N7O8S: C, 48.26; H, 4.60; N, 17.91. Found: C, 48.17; H,
4.58; N, 17.94.

Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
557
3.8.4. 5-[1-(4-Methoxyphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
3.9.2. 5-[1-(4-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-
D
-xylopyranosyl)-1,3,4-thiadiazole-2-
N-xylopyranosyl-1,3,4-oxadiazol-2-amine (8b)
amine (7d)
White solid, yield 71%, mp 188–191 °C; 1H NMR (CD3OD,
400 MHz): d 1.54–3.52 (m, 3H, O–H); 2.50 (s, 3H, CH3), 3.85 (t,
J = 11.1 Hz, 1H, C4–H), 4.04–4.08 (m, 1H, C5–Ha), 4.55–4.57 (m,
2H, C5–Hb, C2–H), 4.59–4.62 (m, 1H, C3–H), 4.81–4.83 (m, 1H,
C1–H), 4.96 (s, 2H, CH2), 7.48–7.63 (m, 4H, ArH); 13C NMR (CD3OD,
150 MHz): d 160.23, 155.73, 154.29 (C@N), 145.58, 130.26, 125.17,
114.38 (phenyl-C), 82.67 (C1), 71.46 (C3), 65.31 (C5), 63.22 (C4),
White solid, yield 41%, mp 202–203.5 °C; 1H NMR (CDCl3,
400 MHz):
d
1.97, 2.05, 2.06 (3s, 9H, CH3CO), 3.53 (t,
J = 10.8 Hz, 1H, C4–H), 3.88 (s, 3H, OCH3), 4.12 (dd, J = 11.1,
6 Hz, 1H, C5–Ha), 4.82 (s, 2H, SCH2), 4.95–4.98 (m, 2H, C5–Hb,
C2–H), 5.01–5.04 (m, 1H, C3–H), 5.31(m, 1H, C1–H), 5.78 (br,
1H, NH), 7.04–7.45 (m, 4H, ArH); 13C NMR (CDCl3, 150 MHz): d
176.87, 174.35, 170.77 (C@O), 165.43, 154.36, 147.52 (C@N),
131.55, 129.14, 112.22 (phenyl-C), 80.29 (C1), 70.65 (C5), 65.42
(C3), 61.38 (C4), 53.17 (C2), 31.45 (SCH2), 24.64, 21.76, 20.12
58.23 (C2), 49.89 (SCH2); IR (KBr)
m: 3300 (O–H, N–H), 1556,
1507, 1434 (C@N, Aryl), 1246 (N–N@C), 1060 (C–O–C), 901 (C1–
H) cmꢀ1; ESIMS: m/z (%) 460 (59, [M+23]+), 438 (47, [M+H]+); Anal.
Calcd for C16H19N7O4S2: C, 43.93; H, 4.38; N, 22.41. Found: C,
44.01; H, 4.36; N, 22.37.
(CH3); IR (KBr)
m: 3250 (N–H), 1745 (C@O), 1553, 1490, 1429
(C@N, Aryl), 1224 (N–N@C), 1037 (C–O–C), 905 (C1–H) cmꢀ1
;
ESIMS: m/z (%) 602 (17, [M+23]+), 580 (14, [M+H]+). Anal. Calcd
for C22H25N7O8S2: C, 45.59; H, 4.35; N, 16.92. Found: C, 45.50;
H, 4.37; N, 16.87.
3.9.3. 5-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-xylopyranosyl-1,3,4-oxadiazol-2-amine (8c)
White solid, yield 74%, mp 219–220 °C; 1H NMR (CD3OD,
400 MHz): 3.17 (t, J = 11.0 Hz, 1H, C4–H), 3.67–3.71 (m, 1H, C5–
Ha), 4.13–4.16 (m, 1H, C5–Hb), 4.52–4.55 (m, 1H, C2–H), 4.59–
4.63 (m, 1H, C3–H), 4.70 (d, J = 8.4 Hz, 1H, C1–H), 4.85 (s, 2H,
CH2), 7.63 (d, J = 8.8 Hz, 2H, ArH), 7.70 (d, J = 8.8 Hz, 2H, ArH);
13C NMR (CD3OD, 150 MHz): d 163.52, 160.25, 154.71 (C@N),
142.18, 131.57, 125.61, 120.07 (phenyl-C), 85.21 (C1), 74.58 (C3),
3.8.5. 5-[1-(2-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-(2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-1,3,4-thiadiazole-2-
amine (7e)
White solid, yield 38%, mp 194–196 °C; 1H NMR (CDCl3,
400 MHz): d 1.96, 2.08, 2.17 (3s, 9H, CH3CO), 2.48 (s, 3H, CH3),
3.49 (t, J = 10.8 Hz, 1H, C4–H), 4.14 (dd, J = 11.7, 5.7 Hz, 1H, C5–
Ha), 4.80 (d, J = 15 Hz, 1H, SCHa), 4.84 (d, J = 15 Hz, 1H, SCHb),
4.96–4.97 (m, 2H, C5–Hb, C2–H), 4.99–5.03 (m, 1H, C3–H),
5.31–5.35 (m, 1H, C1–H), 6.50 (br, 1H, NH), 7.23–7.52 (m, 4H,
71.46 (C5), 63.24 (C4), 58.27 (C2), 50.43 (SCH2); IR (KBr) m: 3254
(O–H, N–H), 1551, 1507, 1431 (C@N, Aryl), 1245 (N–N@C), 1058
(C–O–C), 899 (C1–H) cmꢀ1; ESIMS: m/z (%) 480 (20, [M+23]+),
458 (58, [M+H]+); Anal. Calcd for C15H16ClN7O4S2: C, 39.34; H,
3.52; N, 21.41. Found: C, 39.27; H, 3.50; N, 21.46.
ArH); 13C NMR (CDCl3, 150 MHz):
d 170.88, 169.79, 169.76
(C@O), 168.69, 155.97, 154.49 (C@N), 135.32, 131.89, 131.68,
131.56, 127.36, 126.65 (phenyl-C), 84.81(C1), 71.76(C5), 70.68
(C3), 68.77 (C4), 64.09 (C2), 31.15 (SCH2), 20.69, 20.65, 17.45
3.9.4. 5-[1-(4-Methoxyphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-xylopyranosyl-1,3,4-oxadiazol-2-amine (8d)
(CH3); IR (KBr)
m: 3224 (N–H), 1742 (C@O), 1566, 1510 (C@N,
Aryl), 1223 (N–N@C), 1037 (C–O–C), 908 (C1–H) cmꢀ1; ESIMS:
White solid, yield 63%, mp 139–142 °C; 1H NMR (CD3OD,
400 MHz): d 3.43 (s, 3H, OCH3), 3.59 (t, J = 10.8 Hz, 1H, C4–H),
4.18–4.21 (m, 1H, C5–Ha), 4.88 (s, 2H, SCH2), 4.99–5.03 (m, 2H,
C5–Hb, C2–H), 5.05–5.08 (m, 1H, C3–H), 5.31(m, 1H, C1–H), 5.82
(br, 1H, NH), 7.24–7.47 (m, 4H, ArH); 13C NMR (CD3OD,
m/z (%) 586 (28, [M+23]+), 564 (20, [M+H]+). Anal. Calcd for
C22H25N7O7S2: C, 46.88; H, 4.47; N, 17.40. Found: C, 46.81; H,
4.45; N, 17.45.
3.9. General procedure for the preparation of 5-(1-aryl-1H-
tetrazol-5-ylsulfanylmethyl)-N-xylopyranosyl-1,3,4-oxadiazol-
2-amine 8a–8e and 5-(1-aryl-1H-tetrazol-5-ylsulfanylmethyl)-
N-xylopyranosyl-1,3,4-thiadiazole-2-amine 9a–9e
150 MHz):
126.42, 119.12 (phenyl-C), 80.05 (C1), 71.63 (C3), 67.53 (C5),
61.38 (C4), 59.21 (C2), 49.65 (SCH2); IR (KBr) : 3351 (N–H, O–
H), 2927 (C–H), 1534, 1497, 1429 (C@N, Aryl), 1237 (N–N@C),
1058 (C–O–C) cmꢀ1; ESIMS: m/z (%) 476 (25, [M+23]+), 454 (34,
[M+H]+); Anal. Calcd for C16H19N7O5S2: C, 42.38; H, 4.22; N,
21.62. Found: C, 42.29; H, 4.24; N, 21.67.
d 160.46, 160.09, 156.42 (C@N), 155.17, 143.15,
m
To
a solution of the corresponding compounds 6 and 7
(0.05 mmol) in MeOH (5 mL) was added NaOMe (0.1 M, 0.2 mL),
and the reaction mixture was stirred at room temperature for
0.5 h until TLC (CHCl3/MeOH 5:1, v/v) revealed complete consump-
tion of starting material. The reaction mixture was concentrated
under reduced pressure to afford the White solid. The crude prod-
uct was further purified by flash chromatography on a silica gel
column chromatograph (eluent: CHCl3–MeOH, 4:1, v/v) to obtain
8–9.
3.9.5. 5-[1-(2-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-xylopyranosyl-1,3,4-oxadiazol-2-amine (8e)
White solid, yield 71%, mp 116–118 °C; 1H NMR (CD3OD,
400 MHz): d 2.35 (s, 3H, CH3), 3.78 (t, J = 10.8 Hz, 1H, C4–H),
4.20–4.24 (m, 1H, C5–Ha), 4.92 (s, 2H, SCH2), 5.03–5.06 (m, 2H,
C5–Hb, C2–H), 5.13–5.17 (m, 1H, C3–H), 5.38–5.43 (m, 1H, C1–
H), 7.02–7.47 (m, 4H, ArH), 8.76 (br, 1H, NH); 13C NMR (CD3OD,
3.9.1. 5-(1-Phenyl-1H-tetrazol-5-ylsulfanylmethyl)-N-
xylopyranosyl-1,3,4-oxadiazol-2-amine (8a)
150 MHz):
124.90, 120.18 (phenyl-C), 83.46 (C1), 73.46 (C3), 70.55 (C5),
69.92 (C4), 68.39 (C2), 55.16 (SCH2); IR (KBr) : 3272 (O–H, N–
H), 1550, 1502, 1461 (C@N, Aryl), 1245 (N–N@C), 1051 (C–O–C),
895 (C1–H) cmꢀ1; ESIMS: m/z (%) 438 (42, [M+H]+), 460 (35,
[M+23]+); Anal. Calcd for C16H19N7O4S2: C, 43.93; H, 4.38; N,
22.41. Found: C, 43.82; H, 4.40; N, 22.46.
d 161.58, 158.47, 154.86 (C@N), 150.32, 130.25,
White solid, yield 59%, mp 170–172 °C; 1H NMR (CD3OD,
400 MHz): d 1.20–3.10 (m, 3H, O–H); 3.81 (t, J = 11.1 Hz, 1H, C4–
H), 4.15–4.17 (m, 1H, C5–Ha), 4.78 (s, 2H, SCH2), 4.95–4.98 (m,
2H, C5–Hb, C2–H), 5.00–5.04 (m, 1H, C3–H), 5.19–5.22 (m, 1H,
C1–H), 7.57–7.74 (m, 5H, ArH), 8.11 (br, 1H, NH); 13C NMR (CD3OD,
150 MHz): d 163.54, 155.74, 149.36 (C@N), 139.11, 130.70, 127.65
(phenyl-C), 80.45 (C1), 75.24 (C3), 70.18 (C5), 60.55 (C4), 56.13
m
3.9.6. 5-(1-Phenyl-1H-tetrazol-5-ylsulfanylmethyl)-N-
xylopyranosyl-1,3,4-thiadiazole-2-amine (9a)
(C2), 50.21 (SCH2); IR (KBr)
m: 3339 (O–H, N–H), 1595, 1556,
1504, 1459 (C@N, Aryl), 1287 (N–N@C), 1049 (C–O–C) cmꢀ1
;
White solid, yield 75%, mp 109–111 °C; 1H NMR (DMSO-d6,
400 MHz): d 3.36 (t, J = 11 Hz, 1H, C4–H), 4.15–4.19 (m, 1H, C5–
Ha), 4.78 (s, 2H, SCH2), 4.99–5.05 (m, 2H, C5–Hb, C2–H), 5.14–
5.21 (m, 1H, C3–H), 5.40–5.43 (m, 1H, C1–H), 6.67 (br 1H, NH),
ESIMS: m/z (%) 424 (39, [M+H]+), 446 (62, [M+23]+); Anal. Calcd
for C15H17N7O4S2: C, 42.54; H, 4.05; N, 23.15. Found: C, 42.63; H,
4.07; N, 23.09.

558
Y.-W. He et al. / Carbohydrate Research 346 (2011) 551–559
7.58 (s, 5H, ArH); 13C NMR (DMSO-d6, 150 MHz): d 153.67, 150.45
(C@N), 137.12, 130.87, 131.06, 125.35 (phenyl-C), 72.14 (C3), 70.37
Calcd for C16H19N7O5S: C, 45.60; H, 4.54; N, 23.27. Found: C,
45.51; H, 4.56; N, 23.31.
(C5), 66.75 (C4), 50.43 (C2), 49.17 (SCH2); IR (KBr) m: 3256 (O–H,
N–H), 1640, 1499 (C@N, Aryl), 1240 (N–N@C), 1044 (C–O–C)
cmꢀ1; ESIMS: m/z (%) 430 (55, [M+23]+), 408 (37, [M+H]+); Anal.
Calcd for C15H17N7O5S: C, 44.22; H, 4.21; N, 24.07. Found: C,
44.15; H, 4.23; N, 24.13.
3.10. Biological activity
3.10.1. Antibacterial activity assays
Strains: S. aureus, Escherichia coli and C. albicans.
Method: All used bacteria inoculated into liquid medium. (The
C. albicans were inoculated into Sandburg culture media), cultured
on 37 °C to OD600 value 0.6–0.8. Bacterial suspension 400 lL and
solid medium (containing 1.5% agar) 100 mL were mixed on
55 °C, paved at the plate, was reserved it on 4 °C awaiting congeal-
ing. The 20 lL (100 mmol/L) of sample was dripted to the 2 mm
diameter holes of plate, cultured 18–24 h on 37 °C (C. albicans cul-
tured 48 h), the size of inhibition zone was measured.
3.9.7. 5-[1-(4-Methylphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-xylopyranosyl-1,3,4-thiadiazole-2-amine (9b)
White solid, yield 73%, mp 132–133 °C; 1H NMR (CD3OD,
400 MHz): d 2.48 (s, 3H, CH3), 3.44 (t, J = 10.8 Hz, 1H, C4–H),
4.15–4.20 (m, 1H, C5–Ha), 4.83 (s, 2H, SCH2), 5.05–5.09 (m, 2H,
C5–Hb, C2–H), 5.21–5.24 (m, 1H, C3–H), 5.44–5.47 (m, 1H, C1–
H), 5.79 (br 1H, NH), 7.27–7.41 (m, 4H, ArH); 13C NMR (CD3OD,
150 MHz):
137.46, 118.65 (phenyl-C), 83.47 (C1), 72.09 (C3), 69.18 (C5),
63.42 (C4), 60.79 (C2), 51.16 (SCH2); IR (KBr) : 3327 (N–H, O–
d 163.08, 154.27, 150.38 (C@N), 147.59, 144.25,
3.10.2. PTP1B enzyme inhibition assay
m
PTP1B reaction system contained 5 mM pNPP, 0.09 lM his-
H), 1530, 1421 (C@N, Aryl), 1231 (N–N@C), 1076 (C–O–C) cmꢀ1
;
PTP1B1–321 and buffer containing 20 mM HEPES, 150 mM NaCl,
and 1 mM EDTA (pH 7.0). After incubation of extracts for 10 min,
the reaction was initiated by addition of pNPP. The amount of pro-
duced pNP was measured by detecting absorbance at 405 nm using
microplate spectrophotometer (SpectraMax M5/M5e). IC50 value
was calculated by fitting data with Origin software.
ESIMS: m/z (%) 444 (57, [M+23]+), 422 (48, [M+H]+); Anal. Calcd
for C16H19N7O5S: C, 45.60; H, 4.54; N, 23.27. Found: C, 45.69; H,
4.52; N, 23.21.
3.9.8. 5-[1-(4-Chlorophenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-xylopyranosyl-1,3,4-thiadiazole-2-amine (9c)
White solid, yield 68%, mp 113–115 °C; 1H NMR (CD3OD,
400 MHz): d 0.93–2.20 (m, 3H, O–H), 3.50 (t, J = 11.0 Hz, 1H, C4–
H), 4.05–4.09 (m, 1H, C5–Ha), 4.46–4.49 (m, 2H, C5–Hb, C2–H),
4.52–4.55 (m, 1H, C3–H), 5.62–5.64 (m, 1H, C1–H), 4.73 (s, 2H,
CH2), 7.65–7.72 (m, 4H, ArH), 7.94 (br, 1H, NH); 13C NMR (CD3OD,
150 MHz): d 160.32, 158.73, 150.45 (C@N), 137.28, 129.67, 123.51,
117.61 (phenyl-C), 80.24 (C1), 71.22 (C3), 70.96 (C5), 65.34 (C4),
Acknowledgments
This work was supported by the China National Founds for Dis-
tinguished Young Scientists (Grant No. 30925045), Research Sup-
ported by the CAS/SAFEA International Partnership Program for
Creative Research Teams, National Natural Science Foundation of
China (Grant No. 20462006) and Xinjiang Laboratory of Plant Re-
sources and Natural Products Chemistry Key Lab of Autonomous
Region. We are grateful to the National Center of China for Drug
60.13 (C2), 51.73 (SCH2); IR (KBr)
m: 3373 (O–H, N–H), 1639,
1584, 1495 (C@N, Aryl), 1243 (N–N@C), 1053 (C–O–C) cmꢀ1
;
ESIMS: m/z (%) 464 (95, [M+23]+), 442 (46, [M+H]+); Anal. Calcd
for C15H16ClN7O5S: C, 40.77; H, 3.65; N, 22.19. Found: C, 40.70;
H, 3.66; N, 22.24.
Screening for the a 1B adrenergic receptor agonist activity test
and Dr. Jun Dou in Xinjiang Laboratory of Plant Resources and Nat-
ural Products Chemistry Key Lab of Autonomous Region for the test
of PTP1B inhibition and microorganism inhibition.
3.9.9. 5-[1-(4-Methoxyphenyl)-1H-tetrazol-5-ylsulfanylmethyl]-
N-xylopyranosyl-1,3,4-thiadiazole-2-amine (9d)
Supplementary data
White solid, yield 76%, mp 128–130 °C; 1H NMR (CD3OD,
400 MHz): d 0.90–3.52 (m, 3H, O–H), 3.64 (t, J = 10.8 Hz, 1H,
C4–H), 3.88 (s, 3H, OCH3), 4.05–4.19 (m, 1H, C5–Ha), 4.34 (br,
1H, NH); 4.69 (s, 2H, SCH2), 4.85–4.89 (m, 2H, C5–Hb, C2-H),
4.91–4.95 (m, 1H, C3–H), 5.13 (d, J = 8.8 Hz, 1H, C1–H), 7.18–
Complete crystallographic data for the structural analysis of
compounds 2e, 3e, 5a, and 5c have been deposited with the Cam-
bridge Crystallographic Data Centre, CCDC numbers 2e: 689056,
3e: 689055, 5a: 688446, 5c: 689054. Copies of this information
may be obtained free of charge from the Director, Cambridge Crys-
tallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK
(Tel.: +44 01223 762910, fax: +44 01223 336033, e-mail: depos-
it@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk). Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.carres.2011.01.010.
7.56 (m, 4H, ArH); 13C NMR (CD3OD, 150 MHz):
d 163.89,
161.47, 156.81 (C@N), 152.92, 125.96, 125.82, 114.72 (phenyl-
C), 84.76 (C1), 72.52 (C3), 69.62 (C5), 67.11 (C4), 54.86 (C2),
48.01 (SCH2); IR (KBr)
m: 3385 (N–H, O–H), 1564, 1520, 1433
(C@N, Aryl), 1228 (N–N@C), 1065 (C–O–C) cmꢀ1; ESIMS: m/z
(%) 460 (15, [M+23]+), 438 (25, [M+H]+); Anal. Calcd for
C16H19N7O6S: C, 43.93; H, 4.38; N, 22.41. Found: C, 43.82; H,
4.36; N, 22.46.
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