Dehydrative Thioglycosylation of 1-Hydroxyl Glycosides Catalyzed by In Situ-Generated AlI3

Article abstract of DOI:10.1002/jccs.201600828

Thioglycosylation of 1-hydroxyl glycosides catalyzed by in situ-generated AlI₃ from elemental aluminium and molecular iodine has been developed. This method provides an alternative route to access anomeric thioglycosides without the use of hazard Lewis acidic activators or per-modified activated thiol sources. The major advantages of this dehydrative procedure are environmental friendly, ease of operation, high anomeric diastereoselectivity, and mild reaction conditions.

Full text of DOI:10.1002/jccs.201600828

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Article
Dehydrative Thioglycosylation of 1-Hydroxyl Glycosides Catalyzed
1
by In Situ-Generated AlI3
*
Shiue-Shien Weng, Kun-Yi Hsieh and Zih-Jian Zeng
Department of Chemistry, ROC Military Academy, Kaohsiung 830, Taiwan, ROC
(Received: November 23, 2016; Accepted: January 4, 2017; DOI: 10.1002/jccs.201600828)
Thioglycosylation of 1-hydroxyl glycosides catalyzed by in situ-generated AlI3 from elemental alu-
minium and molecular iodine has been developed. This method provides an alternative route to
access anomeric thioglycosides without the use of hazard Lewis acidic activators or per-modified
activated thiol sources. The major advantages of this dehydrative procedure are environmental
friendly, ease of operation, high anomeric diastereoselectivity, and mild reaction conditions.
Keywords: Dehydrative thioglycosylation; In situ-generated AlI3; 1-Hydroxyl glycosides;
Thioglycosides.
INTRODUCTION
of glycosyl halides in advance, thus limiting its
application.
Sulfur-containing glycoconjugates, glycolipids,
and glycopeptides play essential roles in many biologi-
cal transformations.1 Because thioglycosidic linkages
exhibit high stability toward chemical or enzymatic
hydrolysis and anomerization compared to their O-
glycosidic counterparts,2 S-glycans are commonly used
as O-glycan mimics to study therapeutics, protein inter-
actions, and signal transactions.3 In addition, by taking
advantage of the tunable reactivity of different anome-
ric thiol substituents toward the activator, thioglyco-
sides have been widely utilized as universal building
blocks in the sequential, programmable one-pot synthe-
sis of oligosaccharides.4 As such, the development of
sustainable and more efficient methods for the prepara-
tion of thioglycosides is of great interest. One of the
most conventional methods to produce thioglycosides is
the direct thiolysis of peracetylated sugar derivatives in
the presence of Lewis acids or acidic activators includ-
ing TiCl4,5 BF3-Et2O,6 ZrCl4,7 SnCl4,8 MoO2Cl2,9
TMSOTf-Me3SiSMe,10 ZnI2,11 AlCl3,12 In(OTf )3,13 Fe/
I2,14 Al/I2,15 Et3SiH/I2,16 Me3SiSiMe3/I2,17 p-TSA,18
Amberlyst resin,19 and silica-supported perchloric
acid.20 The sequential multistep SN2 substitution of gly-
cosyl halide with the basic H2S equivalent or Na2S in
the presence of a suitable promoter also serves as a
complementary approach for the synthesis of glycosyl
thiol derivatives.21,22 However, this nucleophilic reac-
tion requires additional procedures for the preparation
On the contrary, the direct dehydrative thioglyco-
sylation of 1-hydroxy glycosides is more fascinating
because it allows for the synthesis of diversified sulfur-
containing core units for the construction of complex
glycans.23 However, the traditional approach of
appending thioglycoside units to 1-hydroxy sugars with
thiols requires the use of stoichiometric dehydration
reagents such as disulfide/phosphine,24 (CF3SO2)2O,25
chlorothiophosphonic esters,26 CBr4/PPh3,27 thionyl
halides/Ag(I),28 DCC/Cu(I),29 and TMSCl/Zn(OTf )2,30
which do not meet the requirements of green chemistry
because a significant amount of toxic and undesired
waste is produced during the reaction. Alternatively,
employing moisture-sensitive or precious reagents such
as SnCl4,31 BF3,32 ytterbrium(OTf )3/2-methoxyacetic
acid,33 p-TSA,34 and In(OTf )3 is a greener method to
19
achieve high conversion and avoid the production of
waste; nevertheless, these protocols are also hazardous
and toxic, and premodified, expensive activated thiol
derivatives are sometimes required, thus making these
methods harsher and restricting their utility.
Notable methods using safer hexamethyldisilane
or triethyl silane reagents coupled with molecular iodine
as a Lewis acid have improved the inherently inert thio-
glycosylation process through their operational simplic-
ity and efficiency. Because α-glycosyl iodide is involved
in the reaction, high stereoselectivities are also achieved
*Corresponding author: Email: wengss@mail.cma.edu.tw
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Article
Weng et al.
in these thiolysis manipulations. We have previously
developed thioglycosylation reactions of peracetylated
sugars by employing nontoxic and environmentally
benign, in situ-generated FeI3 and AlI3 catalyst systems.
In this study, we further expand the utility of this inex-
pensive, nontoxic, and useful catalytic system using Al
metal and molecular I2 in the dehydrative thioglycosy-
lation of 1-hydroxy sugars.
ZnI2 and alkali MgI2 performed sluggishly with low
productivities,35 and the product 1a was obtained in
only 24 and 11% yields, respectively (Table 1, entries
3 and 4). In situ-generated CeI3 from CeCl3 and NaI
showed inactive efficiency (Table 1, entry 5).
36
Next, the studies were continued by screening
other metal iodides. The yield significantly improved in
the presence of 20 mol% FeI3,14 and the product 1a
was obtained in 58% yield (Table 1, entry 6). With the
35
exception of InI3 (Table 1, entry 7), the group IIIa
RESULTS AND DISCUSSION
species provided the best reactivity. BI3 generated from
NaBH4 and I2 afforded 1a in 67% yield, although this
Screening of catalyst and optimized condition
37
To investigate this promising catalytic system, a
series of in situ-generated metal iodides were screened
for a model thioglycosylation reaction between 1.5
equiv of benzenethiol and an anomeric mixture of 1-
hydroxyl-2,3,4,6-tetraacetyl glucoside (α/β = 36/64) in
CH2Cl2 at room temperature under N2 atmosphere for
2 h. The reaction of 20 mol% in situ-generated TMSI
with both (Me3Si)2 and Et3SiH showed incomplete cat-
alytic reactivity (Table 1, entries 1 and 2), providing the
thioglucoside 1a in 43 and 41% yields, respectively.
procedure is toxic (Table 1, entry 8). Nontoxic AlI3
showed the best reactivity,15 providing 1a in 71% yield
with exclusive β-diastereoselectivity (Table 1, entry 9).
The best yield was obtained by employing 30 mol%
AlI3 to afford 1a in 82% yield (Table 1, entry 10). It is
noteworthy that β-anomeric diastereoselectivity was
observed in the reactions because α-geometrical inter-
mediary glycosyl iodide and neighboring 2-acetate
group might be involved in these transformations. In
Table 1. Catalyst screening
OAc
OAc
Catalyst
O
+
SH
O
AcO
AcO
AcO
AcO
SPh
CH2Cl2
rt, 2h
OH
OAc
α/β=33/67
OAc
1a
Entry
Catalyst
Solvent
Yielda
1b
20 mol% (Me3Si)2/20 mol% I2
20 mol% Et3SiH/20 mol% I2
20 mol% Zn/10 mol% I2
20 mol% Mg/60 mol% I2
20 mol% CeCl3/60 mol% NaI
20 mol% Fe/30 mol% I2
20 mol% In/30 mol% I2
20 mol% NaBH4/80 mol% I2
20 mol% Al/30 mol% I2
30 mol% Al/45 mol% I2
30 mol% Al/45 mol% I2
30 mol% Al/45 mol% I2
30 mol% Al/45 mol% I2
30 mol% Al/45 mol% I2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
EtOAc
THF
43
41
24
11
6
58
38
67
71
82
67
55
38
16
2b
3b
4b
5b
6b
7b
8b
9b
10c
11c
12c
13c
14c
DMF
Toluene
a Isolated yield.
b Reaction conditions: 1-hydroxyl-2,3,4,6-tetraacetate (0.5 mmol), silane or metal powder (20–30 mol%), I2 or NaI (10–60 mol
%), para-thiocresol (0.75 mmol), 2.5 mL of solvent, room temperature, N2 atmosphere, 2 h.
c Reaction conditions: 1-hydroxyl-2,3,4,6-tetraacetate (0.5 mmol), Al powder (30 mol%), I2 (45 mol%), 2.5 mL of solvent, room
temperature, N2 atmosphere, 2 h.
2
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Dehydrative Thioglycosylation of 1-Hydroxyl Sugars
Table 2. The scope of thiol nucleophile
OAc
O
30 mol% Al(s)
45 mol% I2
CH2Cl2
rt, 2h
OAc
O
AcO
AcO
+
OH
SR
R
SH
AcO
AcO
OAc
OAc
α/β=33/67
Entry
R
Product
Yielda
1b
2b
3b
4b
5b
6c
4-Me-C6H4-
2-Me-C6H4-
4-MeO-C6H4-
4-Cl-C6H4-
2-Naphthyl-
PhCH2-
CH3CH2-
(CH3)2CH-
Cyclohexyl-
tert-Butyl-
AcSH
1b
1c
1d
1e
1f
1g
1h
1i
81
77
62
79
80
85
84
79
82
45
73
13
7c
8c
9c
1j
1k
1l
10c
11c
12c
AcSK
1l
a Isolated yield.
b Reaction conditions: 1-hydroxyl-2,3,4,6-tetraacetate (0.5 mmol), Al powder (30 mol%), I2 (45 mol%), 2.5 mL of solvent, room
temperature, N2 atmosphere, 2 h.
c 2.5 equiv of thiol was used.
addition, the formation of metal oxides (e.g., ZnO,
In2O3, Al2O3, and Fe2O3) was also observed after the
basic and aqueous termination of the reactions. These
results implied that the dehydrative process might pro-
ceed through an interaction between the 1-hydroxyl
group and the metal iodide. Furthermore, the metal
iodide might also serve as a Lewis acid catalyst because
the use of catalytic amounts of metal iodide could
achieve moderate yields. The solvent effect strongly
influences the yield in the dehydrative thiolysis process.
It was found that oxygenated solvents such as EtOAc,
THF, and DMF deactivated the reactions (Table 1,
entries 11–13). The less polar toluene solvent showed
the worst reactivity, probably due to the incomplete for-
mation of AlI3 and the poor solubility of 1-hydroxyl
glucoside (Table 1, entry 14).
similar reactivity to benzenethiol (Table 2, entry 1). The
more sterically hindered ortho-substituted methyl group
slightly influenced the reaction (Table 2, entry 2). The
reaction of 4-methoxyphenyl mercaptan was sluggish,
and only 62% of the desired product 1d was obtained
(Table 2, entry 3), as the deprotection of the methoxy
group was observed during the reaction. Both 4-chloro-
and 2-naphthyl thiols were suitable substrates for this
manipulation, affording 1e and 1f in excellent yields
(Table 2, entries 4 and 5). We next screened the reac-
tions of more nucleophilic aliphatic thiols. It was found
that the aliphatic thiols were indeed more efficient than
the aromatic ones, providing the thioglycosides 1g–1j in
excellent yields (Table 2, entries 6–9). However, 2.5
equiv of aliphatic thiol is needed to achieve high yields
because of the fast disulfide formation that occurred
under the reaction conditions. The sterically encum-
bered tert-butyl mercaptan was a poor substrate for this
transformation (Table 2, entry 10), and the desired
product 1k was obtained in only 45% yield due to steric
hindrance. The less nucleophilic thioacetic acid could
also be applied to this dehydrative reaction, although
with decreased conversion (Table 2, entry 11). In
The scope of thiol nucleophile
The application of this methodology to other mer-
captans was also done (Table 2). Aromatic thiols with
different electronic and steric properties were properly
reacted with 1-hydroxyl-2,3,4,6-percatylated glucose
using the AlI3 catalyst to afford the thioglycosides 2–6
in excellent yields. Electron-rich para-thiocresol showed
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
3

Article
Weng et al.
Table 3. The scope of 1-hydroxyl glycosidesa
Entry
1
1-Hydroxyl glycosides
Product
Yield (%)b
71
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
2
OH
SPh
2
81
OAc
O
OAc
Ac
Ac
O
O
O
SPh
AcO
AcO
OH
OH
OAc
OAc
O
3
3
4
84
82
O
AcO
AcO
AcO
AcO
SPh
OAc
OAc
4
OAc
OAc
O
O
SPh
SPh
AcO
AcO
OH
OAc
OAc
O
5
5
6
79
83
O
OH
AcO
AcO
AcO
OAc
AcO
OAc
6
OBz
O
OBz
O
BzO
BzO
BzO
BzO
STol
OH
OBz
OBz
7
7
8
1-Hydroxyl-D-lactose peracetate
77
81
OAc
O
OAc
AcO
O
O
AcO
AcO
SPh
OAc
8
OAc
1-Hydroxyl-D-maltose peracetate
OAc
O
AcO
AcO
OAc
Ac
O
AcO
O
O
SPh
9
OAc
9
66
78
64
76
OAc
O
OAc
O
AcO
AcO
AcO
STol
STol
STol
OH
AcO
NHAc
10
NHAc
OAc
10
11
12
OAc
O
O
AcO
AcO
AcO
OH
AcO
NHTroc
11
NHTroc
OBn
O
OBn
O
BnO
BnO
Bn
O
BnO
OH
OH
OBn
OBn
12
OH
O
O
O
O
HO
HO
O
STol
O
OH
13
13
71
H
OH
O
O
HO
HO
STol
O
O
HO
OH
OH
13
OH
a Reaction conditions: 1-hydroxyl sugar (0.5 mmol), benzenethiol or p-thiocresol (1.5 mmol), Al powder (30 mol%), I2 (45 mol
%), 2.5 mL of solvent, room temperature, N2 atmosphere, 2 h.
b Isolated yield.
4
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Dehydrative Thioglycosylation of 1-Hydroxyl Sugars
OAc
contrast, the potassium salt of thioacetic acid was ineffi-
ciently substituted onto the anomeric center, affording
thioglycoside 1l in low yield (Table 2, entry 12). This
result implies that the SN2 substitution of glycosyl
iodide might not be involved in the reaction and that
the β-anomeric diastereoselectivities of thioglucosides
1a–1l might be dominated by the anchimeric assistance
of the 2-acetyl group.
SH
O
OAc
O
O
30 mol% Al
45 mol% I2
AcO
S
AcO
+
OH
BnO
BnO
AcO
AcO
OAc
BnO
CH2Cl2
rt, 2h
O
O
Bn
OAc
BnO
OCH3
O
Bn
14
15, 72%
OCH3
Scheme 1. Synthesis of S-linked-thiodisaccharide.
We further applied the current dehydrative proto-
col to the direct thioglycosylation of 1-hydroxyl
peracetylated glucose with methyl 2,3,4-tri-O-benzyl-6-
thio-α-D-glucose 14 (Scheme 1). It was found that resid-
ual 6-sulfhydryl group of 14 was smoothly reacted with
anomeric carbon of 14 and afforded the desired
β-(1 ! 6)-S-linked-thiodisaccharide 15 in 72% yield.
The scope of 1-hydroxyl glycosides
To extend the scope and generality of the current
dehydrative thioglycosylation protocol, reactions of
other glycosyl donors were also performed (Table 3). 1-
Hydroxyl peracetyl mannose exhibited anchimeric assis-
tance with 2-axial acetate, affording the α-thioglycoside
2 in 71% yield (Table 3, entry 1). Galactosyl, xylosyl,
and arabinosyl donors were smoothly reacted with ben-
zenethiol to afford the β-thioglycosides 3–5 in 81–84%
yields (Table 3, entries 2–4). Furanosyl D-ribose and 1-
hydroyl perbenzoyl glucose were tolerated under the
reaction conditions, providing products 6 and 7 in excel-
lent yields (Table 3, entries 5 and 6). Disaccharides with
α or β 1 ! 40 glycosidic linkages remained intact under
the reaction conditions and exclusively formed the
β-thioglycosides 8 and 9 in high yields (Table 3, entries
7 and 8). The current protocols tolerated N-acetyl (Ac-)
and N-2,2,2-trichloroethyl carbonate (Troc-) protecting
groups, and the corresponding 2-deoxy-2-N-acetyl and
2-deoxy-2-N-Troc-β-D-glucosides 10 and 11 were
obtained in 66 and 78% yield, respectively (Table 3,
entries 9 and 10). The low conversion of 10 might result
from the strongly coordinated acetamide group and
undesired oxazoline by-product formation. It should be
noted that β-thioglycoside 12 was obtained almost exclu-
sively in moderate yield when perbenzylated 1-hydroxyl
galactose was applied under optimized conditions
(Table 3, entry 11). In this case, we observed that the
benzyl groups were randomly cleaved during the course
of the reaction, thus decreasing the conversion of the
desired product. The anomeric geometry of 12 might
result from the 2-equatorial benzyl group and the
α-geometry of the glucosyl iodide intermediate. The
CONCLUSIONS
In conclusion, we have presented a new and handy
method of dehydrative thioglycosylation of 1-hydroxyl
sugars catalyzed by in situ-generated AlI3. This opera-
tionally simple dehydrative thiolysis reaction gives
rapid access to anomeric thioglycosides using nontoxic
aluminium metal and I2 which meet the recent stan-
dards of green chemistry. The current dehydrative pro-
cesses occur with good to excellent diastereoselectivity,
and afford product yields which provide practical alter-
native to access valuable S-glycosides.
EXPERIMENTAL
General
1H NMR and 13C NMR spectra were recorded on
Jeol JVM-EX400: JEOL Ltd., Tokyo, JAPAN: or Var-
ian Unity INOVA-500 Varian Inc., California USA
spectrometers in deuterochloroform with chloroform as
an internal reference unless otherwise stated. Chemical
shifts are reported in ppm (δ). Coupling constants, J,
are reported in Hz. Electrospray (ESI) mass spectra are
reported with data in the form m/e (intensity relative to
base peak). Analytical TLC was visualized with UV
light or with phosphomolybdic acid (PMA) and
KMnO4 staining agents. Column (flash) chromatogra-
phy was performed using 32–63 m silica gel. Solvents
such as CH2Cl2, THF, EtOAc, and DMF were dried
over CaH2 before use. All reactions were run under
nitrogen or Argon atmosphere and the end products
were isolated as spectroscopically pure materials. The
aluminum (20 μm, spherical powder, 99+%) was
obtained from commercial suppliers, and was used
acetonide
protection
of
1-hydroxyl-2,3,4,6-O-
isopropylidene glucoside and 4,6-O-benzylidene gluco-
side was also applicable, although deprotection of the
acetal occurred after the aqueous workup, and both pro-
vided the corresponding product 13 in high yield
(Table 3, entries 12 and 13).
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
5

Article
Weng et al.
without further treatment. The 1-hydroxyl peracylgly-
cosides were prepared by the transamidation of 1-acyl
group of peracylated glycosides with hydrazinium ace-
tate or primary amine38–40 or purchased from a com-
mercial supplier.
75.8, 74.0, 69.9, 68.2, 62.1, 21.2, 20.7, 20.7, 20.6, 20.6;
ESI MS (C21H26O9S, m/z 454): 477 (M + Na+); white
crystalline; mp 114–116ꢀC; TLC: Rf = 0.32 (ethyl ace-
tate/hexane, 1/2).14
o-Tolyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyra
noside (1c). 1H NMR (CDCl3, 400 MHz): δ 7.49 (d,
1H, J = 7.7 Hz), 7.21–7.13 (m, 3H), 5.20 (t, 1H,
J = 12.0 Hz), 5.10–5.01 (m, 2H), 4.66 (dd, 1H,
J = 10.2 Hz), 4.21 (dd, 1H, J = 12.3 Hz), 4.12 (dd, 1H,
J = 12.3; 2.2 Hz), 3.67 (m, 2H), 2.38 (s, 3H), 2.07 (s,
3H), 2.05 (s, 3H), 2.00 (s, 3H), 1.98 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 170.42, 170.1, 169.3, 169.2,
140.4, 131.8, 130.3, 128.4, 126.53, 86.3, 75.7, 73.9, 70.1,
68.3, 62.2, 20.8, 20.6, 20.6, 20.5, 20.5; ESI MS
(C21H26O9S, m/z 454): 477 (M + Na+); white crystal-
line; mp 114–116ꢀC; TLC: Rf = 0.33 (ethyl acetate/hex-
ane, 1/2).
General procedure for synthesis of thioglycoside from 1-
hydroxyl sugars
To a solution of aluminum powder (20 μm,
spherical powder, 0.15 mmol, 4.5 mg) in anhydrous
CH2Cl2 solution (2 mL) was added I2 (0.225 mmol,
57 mg) at room temperature under nitrogen atmos-
phere. After being stirred for 1 h, the solution became
brown purple and the aluminum powder completely
disappeared. To
pentaacetyl glucose
a
solution of 1-hydroxyl-2,3,4,6-
(0.5 mmol, 174 mg) and
(0.75 mmol, 83 mg, 77 μL) benzenethiol in 2 mL
CH2Cl2 was added. The resulting dark brown mixture
was stirred at ambient temperature for 2 h. The reac-
tion was quenched by adding 3 mL saturated
NaHCO3(aq) solution. The organic layer was sepa-
rated and dried over MgSO4 and filtered. The crude
product was concentrated under reduced pressure and
loaded directly on top of an eluent-filled silica gel col-
umn and purified by flash column chromatography, to
provide 15 in 82% yield (181 mg).
4-Methoxy-phenyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D
1
-glucopyranoside (1d). H NMR (CDCl3, 400 MHz): δ
7.49 (d, 2H, J = 10.8 Hz), 6.84 (d, 2H, J = 10.8 Hz),
5.17 (t, 1H, J = 9.2 Hz), 4.97 (t, 1H, J = 10.0 Hz), 4.87
(t, 1H, J = 9.6 Hz), 4.53 (d, 1H, J = 10.0 Hz), 4.19
(dd, 1H, J = 12.0; 4.4 Hz), 4.15 (dd, 1H, J = 12.3,
2.2 Hz), 3.80 (s, 3H), 3.66 (ddd, 1H, J = 7.2, 4.0,
3.2 Hz), 2.08 (s, 3H), 2.05 (s, 3H), 1.99 (s, 3H), 1.96 (s,
3H); 13C NMR (CDCl3, 100 MHz): δ 170.5, 170.1,
169.3, 169.2, 160.4, 136.5, 120.8, 114.4, 85.6, 75.7, 74.0,
69.9, 68.2, 62.0, 55.3, 20.7, 20.7, 20.5, 20.5; ESI MS
(C21H26O10S, m/z 470): 493(M + Na+); white crystal-
line; mp 92–93ꢀC; TLC: Rf = 0.31 (ethyl acetate/hex-
ane, 1/2).14
Phenyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyra
1
noside (1a). H NMR (CDCl3, 400 MHz): δ 7.51–7.50
(m, 2H), 7.32–7.26 (m, 3H), 5.22 (t, 1H, J = 9.2 Hz),
5.02 (dd,1H, J = 9.8; 9.7 Hz), 4.97 (dd, 1H, J = 10.1;
6.1Hz), 4.70 (d, 1H, J = 10.4 Hz), 4.21–4.19 (m, 2H),
3.72 (m, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.01 (s, 3H),
1.98 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 170.5
170.1, 169.3, 169.2, 133.1, 131.6, 128.9, 128.4, 85.7,
75.8, 73.9, 69.9, 68.2, 62.1, 20.7, 20.7, 20.5, 20.5; ESI
MS (C20H24O9S, m/z 440.46): 463, (M + Na+); white
solid; mp 118–120ꢀC; TLC: Rf = 0.35 (ethyl acetate/
hexane, 1/2).14
4-Chloro-phenyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-
1
glucopyranoside (1e). H NMR (CDCl3, 400 MHz): δ
7.44 (d, 2H, J = 6.4 Hz), 7.27 (d, 2H, J = 6.4 Hz), 5.21
(t, 1H, J = 9.2 Hz), 5.01 (t, 1H, J = 9.6 Hz), 4.93 (t,
1H, J = 10 Hz), 4.64 (d, 1H, J = 10.0 Hz), 4.25–4.11
(m, 2H), 3.71 (ddd, 1H, J = 10.0, 4.8, 2.8 Hz), 2.07 (s,
3H), 2.06 (s, 3H), 2.00 (s, 3H), 1.97 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 170.4, 170.1, 169.3, 169.1, 134.9,
129.4, 85.2, 75.8, 73.8, 69.8, 68.1, 62.0, 20.7, 20.6; ESI
MS (C20H23ClO9S, m/z 474): 497 (M + Na+); white
crystalline; mp 112–113ꢀC; TLC: Rf = 0.36 (ethyl ace-
tate/hexane, 1/2).14
p-Tolyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyra
1
noside (1b). H NMR (CDCl3, 400 MHz): δ 7.39 (d,
2H, J = 8.1 Hz), 7.39 (d, 2H, J = 7.9 Hz), 5.21 (dd,
1H, J = 10.0, 9.4 Hz), 5.03 (dd, 1H, J = 9.4; 9.3 Hz),
4.94 (t, 1H, J = 10.1 Hz), 4.63 (d, 1H, J = 10.0 Hz),
4.21–4.18 (m, 2H), 3.70 (ddd, 1H, J = 10.1, 4.7,
2.7 Hz), 2.35 (s, 3H), 2.09 (s, 3H), 2.08 (s, 3H), 2.01 (s,
3H), 1.98 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
170.6, 170.2, 169.4, 169.2, 138.8, 129.7, 127.6, 85.8,
2-Naphthyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucop
yranoside (1f ). 1H NMR (CDCl3, 400 MHz): δ 7.99
(s, 1H), 7.83–7.77 (m, 3H), 7.57–7.46 (m, 3H), 5.26 (t,
1H, J = 9.7 Hz), 5.11–5.04 (m, 2H), 4.78 (d, 1H,
6
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Dehydrative Thioglycosylation of 1-Hydroxyl Sugars
J = 10.0 Hz), 4.23 (dd, 1H, J = 12.3; 5.1 Hz), 4.18
(dd, 1H, J = 12.3, 2.4 Hz), 3.72 (ddd, 1H, J = 7.4,
4.9, 2.4 Hz), 2.11 (s, 3H), 2.02 (s, 3H), 2.00 (s, 3H),
1.98 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ 170.5,
170.1, 169.3, 169.21, 133.4, 132.9, 132.9, 132.7, 130.2,
128.7, 128.4, 127.7, 126.7, 126.6, 85.8, 75.9, 73.9,
70.0, 68.2, 62.1, 20.7, 20.6, 20.5, 20.5; ESI MS
(C24H26O9S, m/z 490): 513 (M + Na+); white crystal-
line; mp 108–109ꢀC; TLC: Rf = 0.36 (ethyl acetate/
hexane, 1/2).14
Cyclohexyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucop
yranoside (1j). H NMR (CDCl3, 400 MHz): δ 5.21 (t,
1
1H, J = 9.4 Hz), 5.06 (t, 1H, J = 9.9 Hz), 4.98 (t, 1H,
J = 10.1 Hz), 4.59 (d, 1H, J = 10.1 Hz), 4.21 (dd, 1H,
J = 12.3, 5.3 Hz), 4.12 (dd, 1H, J = 12.4, 2.5 Hz), 3.69
(ddd, 1H, J = 10.0, 5.4, 2.5 Hz), 2.89 (m, 2H), 2.06 (s,
3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H), 1.98 (m,
2H), 1.75 (m, 2H), 1.43–1.21 (m, 6H); 13C NMR
(CDCl3, 100 MHz): δ 170.6, 170.2, 169.4, 169.3, 83.2,
75.7, 74.0, 70.3, 68.5, 62.3, 43.9, 34.2, 33.9, 26.0, 25.9,
25.6, 20.7, 20.7, 20.58, 20.56; ESI MS (C20H30O9S, m/z
446): 469 (M + Na+); white solid; mp 120–122ꢀC; TLC:
Rf = 0.40 (ethyl acetate/hexane, 1/2).14
Benzyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyran
1
oside (1g). H NMR (CDCl3, 400 MHz): δ 7.33–7.27
(m, 5H), 5.15–5.03 (m, 3H), 4.28 (d, 1H, J = 9.7 Hz),
4.25 (dd, 1H, J = 12.4; 5.1 Hz), 4.13 (dd, 1H, J = 12.4,
2.3 Hz), 3.94 (d, 1H, J = 12.9 Hz), 3.83 (d, 1H,
J = 12.9 Hz), 3.59 (ddd, 1H, J = 9.7, 5.0, 2.3 Hz), 2.11
(s, 3H), 2.06 (s, 6H), 1.99 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ 170.6, 170.1, 169.4, 169.3, 136.8, 129.0,
128.6, 127.4, 81.9, 75.8, 73.8, 69.6, 62.2, 33.7, 20.7,
20.6, 20.5, 20.5; ESI MS (C21H26O9S, m/z 454):
477 (M + Na+); white crystalline; mp 98–99ꢀC; TLC:
Rf = 0.38 (ethyl acetate/hexane, 1/2).14
Tert-butyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopy
1
ranoside (1k). H NMR (CDCl3, 400 MHz): δ 5.25 (t,
1H, J = 9.3 Hz), 5.03 (t, 1H, J = 9.7 Hz), 4.94 (t, 1H,
J = 9.8 Hz), 4.63 (d, 1H, J = 10.0 Hz), 4.19 (dd, 1H,
J = 12.2, 6.0 Hz), 4.10 (dd, 1H, J = 12.2, 2.2 Hz), 3.71
(ddd, 1H, J = 6.4, 6.0, 2.3 Hz), 2.04 (s, 3H), 2.03 (s,
3H), 2.02 (s, 3H), 2.0 (s, 3H), 1.36 (s, 9H); 13C NMR
(CDCl3, 100 MHz): δ 170.6, 170.2, 169.4, 169.3, 82.3,
75.6, 74.0, 70.2, 68.6, 62.6, 44.3, 31.4, 20.7, 20.7, 20.58,
20.56; ESI MS (C18H28O9S, m/z 420): 443 (M + Na+);
white solid; mp 140–142ꢀC; TLC: Rf = 0.23 (ethyl ace-
tate/hexane, 1/2).14
Ethyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyrano
1
side (1h). H NMR (CDCl3, 400 MHz): δ 5.22 (t, 1H,
J = 9.2 Hz), 5.06 (t, 1H, J = 10.0 Hz), 5.01 (t, 1H,
J = 10 Hz), 4.48 (d, 1H, J = 10.0 Hz), 4.24 (dd, 1H,
J = 12.0, 3.2 Hz), 4.11 (dd, 1H, J = 12.4, 2.0 Hz), 3.69
(ddd, 1H, J = 10.0, 4.8, 2.4 Hz), 2.74–2.63 (m, 2H),
2.05 (s, 3H), 2.03 (s, 3H), 1.99 (s, 3H), 1.97 (s, 3H); 13C
NMR (CDCl3, 100 MHz): δ 170.6, 170.1, 169.3, 169.3,
83.5, 75.8, 73.9, 69.8, 68.3, 62.1, 24.1, 20.7, 20.5, 20.5,
14.8; ESI MS (C16H24O9S, m/z 392): 415 (M + Na+);
white crystalline; mp 82–83ꢀC TLC: Rf = 0.36 (ethyl
acetate/hexane, 1/2).14
2,3,4,6-Tetra-O-acetyl-1-S-acetyl-1-thio-β-D-glucop
1
yranoside (1l). H NMR (CDCl3, 400 MHz): δ 5.24 (d,
1H, J = 10.0 Hz), 5.14–5.08 (m, 2H), 4.25 (dd, 1H,
J = 12.5; 4.4 Hz), 4.08 (dd, 1H, J = 12.4; 1.6 Hz), 3.83
(dt, 1H, J = 10.0 Hz, J = 1.8 Hz), 2.38 (s, 3H), 2.07 (s,
3H), 2.03 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 192.0, 170.6, 169.9, 169.33,
169.28, 80.1, 76.3, 73.9, 68.9, 67.8, 61.6, 30.8, 20.66,
20.51, 20.3, 20.2; ESI MS (C17H25O10S, m/z 421): 445 -
(M + Na + H +); TLC: Rf = 0.33 (ethyl acetate/hex-
ane, 1/2).14
Iso-propyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopy
1
ranoside (1i). H NMR (CDCl3, 400 MHz): δ 5.20 (t,
1H, J = 9.3 Hz), 5.04 (t, 1H, J = 9.8 Hz), 4.97 (t, 1H,
J = 9.8 Hz), 4.56 (d, 1H, J = 10.1 Hz), 4.20 (dd, 1H,
J = 12.3, 5.3 Hz), 4.10 (m, 1H), 3.68 (ddd, 1H, J = 9.9,
5.2, 2.2 Hz), 3.14 (septet, 1H), 2.04 (s, 3H), 2.02 (s,
3H), 2.01 (s, 3H), 1.99 (s, 3H), 1.98 (s, 3H), 1.27 (dd,
6H, J = 6.6, 4.1 Hz); 13C NMR (CDCl3, 100 MHz): δ
170.5, 170.1, 169.3, 169.3, 83.3, 75.9, 73.8, 70.2, 68.4,
62.2, 35.6, 24.0, 23.7, 20.7, 20.6, 20.53, 20.5; ESI MS
(C17H26O9S, m/z 406): 429 (M + Na+); white solid; mp
108–111ꢀC; TLC: Rf = 0.39 (ethyl acetate/hex-
ane, 1/2).14
Phenyl-2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyr
anoside (2). H NMR (CDCl3, 400 MHz): δ 7.50–7.48
1
(m, 2H), 7.33–7.29 (m, 3H), 5.59 (brs, 1H), 5.36–5.29
(m, 2H), 4,55 (m, 1H), 4.30 (dd, 1H, J = 12.4; 6.0 Hz),
4.10 (dd, 1H, J = 12.4 Hz, J = 2.4 Hz), 2.15 (s, 3H),
2.08 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 170.5, 169.9, 169.8, 169.1, 132.6,
132.0, 129.2, 128.1, 85.7, 70.9, 69.5, 69.4, 66.4, 62.4,
20.9, 20.7, 20.7, 20.6; ESI MS (C20H24O9S, m/z 440):
463 (M + Na+); TLC: Rf = 0.27 (ethyl acetate/hex-
ane, 1/3).14
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
7

Article
Weng et al.
Phenyl-2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyr
anoside (3). H NMR (CDCl3, 400 MHz): δ 7.47–7.45
2H, J = 7.8 Hz), 8.00 (d, 2H, J = 7.8 Hz), 7.92 (d, 2H,
J = 7.8 Hz), 7.82 (d, 2H, J = 7.8 Hz), 7.62 (t, 1H,
J = 7.4 Hz), 7.57–7.40 (m, 9H), 7.36 (t, 2H,
J = 7.7 Hz), 7.28 (t, 2H, J = 7.9 Hz), 6.96 (d, 2H,
J = 7.9 Hz), 5.93 (t, 1H, J = 9.5 Hz), 5.62 (t, 1H,
J = 9.8 Hz), 5.49 (t, 1H, J = 9.8 Hz), 5.01 (d, 1H,
J = 9.9 Hz), 4.71 (dd, 1H, J = 12.2; 2.1 Hz), 4.50 (dd,
1H, J = 12.2; 5.7 Hz), 4.23–4.19 (m, 1H); 13C NMR
(CDCl3, 125 MHz): δ 166.0, 165.8, 165.1, 165.0, 138.6,
133.87, 133.43, 133.27, 133.17, 133.1, 129.82, 129.80,
129.69, 129.60, 129.2, 128.74, 128.67, 128.4, 128.2,
127.5, 86.28, 76.2, 74.2, 70.4, 69.3, 63.1, 21.1; ESIMS
(C41H34IO9, m/z 703): 726 (M + Na+); TLC: Rf = 0.42
(ethyl acetate/hexane, 1/1).14
1
(m, 2H), 7.26–7.24 (m, 3H, aromatic H), 5.36 (d, 1H,
J = 3.2 Hz), 5.18 (t, 1H, J = 10.0 Hz), 5.01 (dd, 1H,
J = 10.0; 3.2 Hz), 4.69 (d, 1H, J = 10.0 Hz), 4.13 (dd,
1H, J = 11.6 Hz, J = 7.2 Hz), 4.06 (dd, 1H,
J = 11.6 Hz, J = 6 Hz), 3.91 (t, 1H, J = 6.8 Hz), 2.05
(s, 3H), 2.03 (s, 3H), 1.97 (s, 3H), 1.91 (s, 3H); 13C
NMR (CDCl3, 100 MHz): δ 170.0, 169.8, 169.6, 169.1,
132.2, 128.6, 127.8, 86.1, 74.1, 71.7, 67.0, 61.4, 20.5,
20.3, 20.3, 20.2; ESIMS (C20H24O9S, m/z 440):
463 (M + Na+); TLC: Rf = 0.33 (ethyl acetate/hex-
ane, 1/2).14
Phenyl-2,3,4-tri-O-acetyl-1-thio-β-D-xylopyranoside
(4). H NMR (CDCl3, 400 MHz): δ 7.50–7.47 (m, 2H),
1
Phenyl-2,3,6-tri-O-acetyl-4-O-(20,30,40,60-tetra-O-
7.33–7.31 (m, 3H), 5.19 (t, 1H, J = 8.2 Hz), 4.90 (t,
1H, J = 8.2 Hz), 4.88 (m, 1H). 4.78 (dd, 1H,
J = 8.3 Hz), 4.28 (dd, 1H, J = 11.8; 4.9 Hz), 3.42 (dd,
1H, J = 12.0, 8.8 Hz), 2.11 (s, 3H), 2.04 (S, 6H); 13C
NMR (CDCl3, 100 MHz): δ 169.9, 169.7, 169.3, 132.7,
132.2, 129.0, 128.2, 86.2, 72.0, 69.8, 68.4, 65.2, 20.8,
20.7; ESIMS (C17H20O7S, m/z 368): 391 (M + Na+);
white crystalline; mp 76–77ꢀC; TLC: Rf = 0.26 (ethyl
acetate/hexane, 1/3).14
acetyl-β-D-galactopyranosyl)-1-thio-β-D-glucopyranoside
(8). 1H NMR (CDCl3, 400 MHz): δ 7.49–7.46 (m,
2H), 7.33–7.27 (m, 3H), 5.34 (dd, 1H, J = 3.4;
1.0 Hz), 5.23 (t, 1H, J = 9.2 Hz), 5.09 (dd, 1H,
J = 10.4; 7.8 Hz), 4.94 (dd, 1H, J = 10.4, 3.4 Hz),
4.88 (dd, 1H, J = 10.0, 9.2 Hz), 4.66 (d, 1H,
J = 10.1Hz), 4.52 (dd, 1H, J = 12.0, 2.0 Hz), 4.46 (d,
1H, J = 8.0 Hz), 4.10 (m, 1H), 4.14–4.04 (m, 2H),
3.85 (bt, 1H, J = 7.2 Hz), 3.63–3.62 (m, 2H), 2.15 (s,
3H), 2.10 (s, 3H), 2.09, (s, 3H), 2.04 (s, 6H), 2.03 (s,
3H), 1.95 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
170.2, 170.2, 170.0, 169.9, 169.6, 169.5, 169.05, 133.0,
131.7, 128.8, 128.2, 100.9, 85.4, 76.15, 73.8, 70.9,
70.7, 70.3, 69.1, 66.6, 62.1, 60.8, 20.72, 20.67, 20.5,
20.4; ESI MS (C32H40O17S, m/z 728): 752 (M + Na+);
white crystalline; mp 170–171ꢀC; TLC: Rf = 0.13
(ethyl acetate/hexane, 1/1).14
Phenyl-2,3,4-tri-O-acetyl-1-thio-β-L-arabinopyranos
1
ide (5). H NMR (CDCl3, 400 MHz): δ 7.49–7.46 (m,
2H), 7.28–7.27 (m, 3H), 5.26–5.20 (m, 1H), 5.23 (t, 1H,
J = 8.2 Hz), 5.09 (dd, 1H, J = 8.44, 3.4 Hz), 4.80 (d,
1H, J = 7.8 Hz), 4.12 (dd, 1H, J = 12.7, 4.2 Hz), 3.65
(dd, 1H, J = 12.7, 2.0 Hz), 2.06 (S, 6H), 2.01 (s, 3H);
13C NMR (CDCl3, 100 MHz): δ 169.9, 169.7, 169.2,
133.1, 132.1, 128.8, 127.7, 86.5, 70.3, 68.3, 67.4, 65.1,
20.6, 30.6, 20.5; ESIMS (C17H20O7S, m/z 368):
391 (M + Na+); TLC: Rf = 0.28 (ethyl acetate/hex-
ane, 1/3).14
Phenyl-2,3,6-tri-O-acetyl-4-O-(20,30,40,60-tetra-O-
acetyl-α-D-glucopyranosyl)-1-thio-β-D-glucopyranoside
1
(9). H NMR (CDCl3, 400 MHz): δ 7.48–7.46 (m, 2H),
Phenyl-2,3,5-tetra-O-acetyl-β-D-ribofuranoside (6).
1H NMR (CDCl3, 400 MHz): δ 7.53–7.51 (m, 2H),
7.34–7.32 (m, 3H), 5.31 (d, 1H, J = 4.8 Hz), 5.26–5.19
(m, 2H), 4.27 (m, 1H). 4.26 (dd, 1H, J = 12.8, 2.8 Hz),
4.09 (dd, 1H, J = 12.8, 5.2 Hz), 2.09 (s, 3H), 2.07 (s,
3H), 2.06 (s, 3H); 13C NMR (CDCl3, 100 MHz): δ
170.5, 169.6, 133.4, 131.7, 129.0, 128.4, 87.9, 80.1, 73.9,
71.4, 63.4, 20.8, 20.5; ESI MS (C17H20O7S, m/z 368):
391 (M + Na+); TLC: Rf = 0.31 (ethyl acetate/hex-
ane, 1/3).14
7.34–7.27 (m, 3H), 5.37 (d, 1H, J = 4 Hz), 5.33 (dd,
1H, J = 10.3, 9.7Hz,), 5.27 (t, 1H, J = 8.9Hz), 5.02
(dd, 1H, J = 10.0; 9.7 Hz), 4.89–4.79 (m, 2H), 4.52 (d,
1H, J = 10.0 Hz), 4.27–4.21 (m, 2H), 4.16 (dd, 1H,
J = 12.4, 7.7 Hz), 4.03 (dd, 1H, J = 12.4, 2.1 Hz),
3.95–3.87 (m, 2H), 3.70 (ddd, 1H, J = 7.5, 4.8, 2.6 Hz),
2.11 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H),
2.01 (s, 3H), 1.98 (s, 3H), 1.97 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 170.49, 170.47, 170.3, 170.1,
169.9, 169.5, 169.4, 133.4, 131.3, 128.9, 128.4, 95.6,
85.1, 76.5, 76.1, 72.6, 70.7, 70.0, 69.3, 68.6, 68.1, 62.9,
61.6, 20.86, 20.83, 20.76, 20.67, 20.63; ESIMS
p-Tolyl-2,3,4,6-tetra-O-benzoyl-1-thio-β-D-glucopyr
1
anoside (7). H NMR (CDCl3, 500 MHz): δ 8.08 (d,
8
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017

JOURNAL OF THE CHINESE
CHEMICAL SOCIETY
Dehydrative Thioglycosylation of 1-Hydroxyl Sugars
(C32H40O17S, m/z 728): 751 (M + Na+); TLC: Rf =
0.12 (ethyl acetate/hexane, 1/1).14
p-Methylphenyl-1-thio-β-D-glucopyranoside
(13).
1H NMR (CDCl3, 400 MHz):
δ
7.46 (d, 2H,
p-Tolyl-2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-
1-thio-β-D-glucopyranoside (10). 1H NMR (CDCl3,
400 MHz): δ 7.39 (d, 2H, J = 8.0 Hz), 7.10 (d, 2H,
J = 8.0 Hz), 5.61 (t, 1H, J = 8.7 Hz), 5.19 (t, 1H,
J = 9.8 Hz), 5.02 (t, 1H, J = 9.7 Hz), 4.69 (d, 1H,
J = 10.4 Hz), 4.19–4.16 (m, 2H), 3.97 (dd, 1H,
J = 9.4 Hz, J = 3.2 Hz), 3.71–3.67 (m, 1H), 2.33 (s,
3H), 2.07 (s, 3H), 2.05 (s, 3H), 2.00 (s, 3H), 1.98 (s,
3H); 13C NMR (CDCl3, 100 MHz): δ 170.9, 170.6,
170.1, 169.3, 132.5, 132.3, 128.8, 127.9, 86.5, 75.6, 73.7,
68.5, 62.4, 53.2, 23.2, 20.7, 20.6, 20.5; ESIMS
(C21H27NO8S, m/z 453): 476 (M + Na+); TLC: Rf =
0.39 (ethyl acetate/hexane, 1/1).14
J = 8.0 Hz), 7.13 (d, 2H, J = 8.0 Hz), 4.58 (bs, 1H,
OH), 4.52 (d, 1H, J = 7.4 Hz), 3.86 (dd, 1H, J = 11.0,
1.4 Hz), 3.68 (t, 1H, J = 2.6 Hz), 3.67 (dd, 1H,
J = 11.1, 4.9 Hz), 3.36–3.26 (m, 2H), 3.20 (t, 1H,
J = 9.6 Hz); 13C NMR (CDCl3, 100 MHz): δ 170.9,
170.6, 170.1, 169.3, 132.5, 132.3, 138.9, 133.6, 131.2,
130.7, 89.7, 82.1, 79.7, 73.8, 71.5, 63.0, 21.2; ESIMS
(C13H18O5S, m/z 286): 309 (M + Na+); TLC: Rf = 0.36
(ethyl acetate, 100%).9
Procedure for synthesis of β-(1 ! 6)-S-linked-thiodisacc
haride 15
To aluminum powder (20 μm, spherical powder,
0.18 mmol, 5.4 mg) in anhydrous CH2Cl2 solution
(2 mL) was added I2 (0.27 mmol, 68 mg) at room tem-
perature under nitrogen atmosphere. After being stirred
for 1 h, the solution became brown purple and the alu-
minum powder completely disappeared. To a solution
of 1-hydroxyl-2,3,4,6-pentaacetyl glucose (0.6 mmol,
209 mg) and 0.5 mmol 2,3,4-tri-O-benzyl-6-thio-α-D-
glucose 14 (0.5 mmol, 240 mg) in 2 mL CH2Cl2, the
above solution was added. The resulting dark brown
mixture was stirred at ambient temperature for 2 h. The
reaction was quenched by adding 3 mL saturated
NaHCO3(aq) solution. The organic layer was separated
and dried over MgSO4 and filtered. The crude product
was concentrated under reduced pressure and loaded
directly on top of an eluent-filled silica gel column and
purified by flash column chromatography to provide 15
in 72% yield (292 mg).
Methyl-2,3,4,-tri-O-benzyl-6-S-(20,30,40,60-tetra-O-
acetyl-β-D-glucopyranosyl)-6-thio-α-D-glucopyranoside
(15).9 1H NMR (CDCl3, 400 MHz) δ 7.37–7.27 (m,
15H), 5.19 (t, J = 9.6, 1H), 5.05 (t, J = 9.6, 1H), 4.95
(t, J = 7.2, 1H), 4.98 (d, J = 11.0, 1H), 4.92 (d, 1H,
J = 11.0), 4.81–4.77 (m, 2H), 4.66 (d, J = 13.2, 1H),
4.64 (d, J = 13.2, 1H), 4.60 (d, J = 7.2, 1H), 4.57 (d,
J = 3.6, 1H), 4.18 (dd, J = 12.4, 4.8, 1H), 4.05 (dd,
J = 12.4, 2.0, 1H), 3.96 (t, J = 9.2, 1H), 3.83 (td,
J = 8.0, 2.0, 1H), 3.59 (ddd, J = 10.0, 4.4, 2.0, 1H),
3.49 (dd, J = 9.6, 3.2, 1H), 3.40 (s, 3H), 3.31 (t, J = 9.2,
1H), 3.00 (dd, J = 13.6, 2.0, 1H), 2.69 (dd, J = 13.6,
8.8, 1H), 2.04 (s, 3H), 2.02 (s, 3H), 2.01 (s, 3H), 2.00 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ 170.6, 170.2,
169.3, 169.1, 138.6, 138.2, 138.1, 128.47, 128.45, 128.37,
p-Methylphenyl-3,4,6-tri-O-acetyl-2-deoxy-1-thio-
2-(2,2,2-trichloroethyloxycarbonylamino)-β-D-
1
glucopyranoside (11). H NMR (CDCl3, 400 MHz): δ
7.41 (d, 2H, J = 8.0 Hz), 7.11 (d, 2H, J = 8.0 Hz), 5.25
(q, 2H, J = 10.0 Hz), 5.01 (t, 1H, J = 10.0 Hz), 4.79
(d, 2H, J = 10.4 Hz), 4.72 (d, 1H, J = 12.0 Hz), 4.22
(dd, 1H, J = 12.4, 5.2 Hz), 4.16 (dd, 1H, J = 12.4,
2.4 Hz), 3.07 (septet, 1H, J = 2.4 Hz), 2.35 (s, 3H),
2.08 (s, 3H), 2.005 (s, 3H), 2.002 (s, 3H); 13C NMR
(CDCl3, 100 MHz): δ 170.59, 170.56, 169.4, 153.8,
138.7, 133.7, 129.7, 127.9, 86.7, 75.8, 74.5, 73.2, 68.5,
62.3, 55.0, 21.2, 20.7, 20.6, 20.56; ESIMS
(C22H26Cl3NO9S, m/z 587): 610 (M + Na+); TLC: Rf =
0.32 (ethyl acetate/hexane, 1/2).41
p-Methylphenyl-2,3,4,6-tetra-O-benzyl-1-thio-β-D-
1
galactopyranoside (12). H NMR (CDCl3, 400 MHz):
δ 7.46 (d, 1H, J = 1.6 Hz), 7.44 (t, 2H, J = 2.0 Hz),
7.41–7.23 (m, 21H), 7.05 (d, 2H, J = 7.6 Hz), 5.69 (d,
1H, J = 5.6 Hz), 5.01 (d, 1H, J = 11.2 Hz), 4.92 (d,
1H, J = 12.0 Hz), 4.82 (d, 1H, J = 11.6 Hz), 4.78 (d,
1H, J = 12.0 Hz), 4.74 (d, 1H, J = 11.6 Hz), 4.63 (d,
1H, J = 11.6 Hz), 4.54 (dd, 1H, J = 4.0 Hz), 4.43 (q,
2H, J = 6.8 Hz), 4.41–4.38 (m, 1H), 4.03 (q, 1H,
J = 1.6 Hz), 3.87 (dd, 1H, J = 10.0, 2.8 Hz),
3.64–3.54 (m, 2H) , 2.32 (s, 3H); 13C NMR (CDCl3,
100 MHz): δ 138.7, 138.6, 138.1, 138.0, 137.1, 123.3,
130.6, 129.6, 128.4, 128.3, 128.27, 128.17, 128.10,
127.9, 127.64, 127.62, 127.56, 127.50, 127.46, 127.41,
87.9, 79.4, 76.5, 75.2, 74.8, 73.4, 73.3, 72.5, 70.2,
68.9,
29.7;
ESIMS
(C41H42O5S,
m/z
647):
670 (M + Na+); TLC: Rf = 0.36 (ethyl acetate/hexane,
1/12).42
J. Chin. Chem. Soc. 2017
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.jccs.wiley-vch.de
9

Article
Weng et al.
19. S. A. Abbas, J. J. Barlow, K. L. Matta, Carbohydr. Res.
1982, 100, C33.
20. G. Agnihotri, P. Tiwari, A. K. Misra, J. Carbohydr.
Chem. 2006, 25, 491.
21. B. D. Johnston, B. M. Pinto, J. Org. Chem. 2000,
65, 4607.
128.0, 127.94, 127.86, 127.83, 127.6, 97.8, 83.9, 81.9,
80.7, 79.9, 75.71, 75.70, 75.0, 73.9, 73.3, 71.0, 70.2,
68.3, 62.0, 55.1, 31.6, 20.61, 20.58, 20.55, 20.51; 810.9;
ESI-MS (C42H50O14S, m/z 810): 833 (M + Na+); TLC
Rf = 0.38 (ethyl acetate/hexane, 1/2).43,44
22. R. T. Dere, A. Kumar, V. Kumar, X. Zhu,
R. R. Schmidt, J. Org. Chem. 2011, 76, 7539.
23. Y.-C. Ko, C.-F. Tsai, C.-C. Wang, V. M. Dhurandhare,
P.-L. Hu, T.-Y. Su, L.-S. Lico, M. M. Zulueta, S.-
C. Hung, J. Am. Chem. Soc. 2014, 136, 14425.
24. D. Gueyrard, A. Tatibouet, Y. Gareau, P. Rollin, Org.
Lett. 1999, 1, 521.
ACKNOWLEDGMENTS
This work was supported by the Ministry of Sci-
ence and Technology ROC, Taiwan (MOST-103-2113-
M-145-001), and the authors declare no competing
financial interest. We thank the Center for Resources
and Development (CRRD), Kaohsiung Medical Uni-
versity for services in NMR analysis.
25. B. A. Garcia, J. L. Poole, D. Y. Gin, J. Am. Chem. Soc.
1997, 119, 7597.
26. M. W. Loranger, S. A. Beaton, K. L. Lines,
D. L. Jakeman, Carbohydr. Res. 2013, 379, 43.
27. T. Ghosh, A. Santra, A. K. Misra, Beilstein J. Org.
Chem. 2013, 9, 974.
28. B. D. Johnston, B. M. Pinto, J. Org. Chem. 2000, 65, 4607.
29. H. Tsutsumi, Y. Ishido, Carbohydr. Res. 1981, 88, 61.
30. B. A. Garcia, D. Y. Gin, J. Am. Chem. Soc. 2000,
122, 4269.
REFERENCES
1. K. Pachamuthu, R. R. Schmidt, Chem. Rev. 2006, 106, 160.
2. E. J. Grayson, S. J. Ward, A. L. Hall, P. M. Rendle,
D. P. Gamblin, A. S. Batsanov, B. G. Davis, J. Org.
Chem. 2005, 70, 9740.
3. P. J. Garegg, Adv. Carbohydr. Chem. Biochem. 1997,
52, 179.
4. Z. Zhang, I. R. Ollmann, X.-S. Ye, R. Wischnat,
T. Baasov, C.-H. Wong, J. Am. Chem. Soc. 1999, 121, 734.
5. C. Malet, J. L. Viladot, A. Ochoa, B. Gallego, C. Brosa,
A. Planas, Carbohydr. Res. 1995, 274, 285.
6. C.-A. Tai, S. S. Kulkarni, S.-C. Hung, J. Org. Chem.
2003, 68, 871.
7. Y. Ding, Synth. Commun. 1999, 20, 3541.
8. K. C. Nicolaou, N. Winssinger, J. Pastor, F. DeRoose,
J. Am. Chem. Soc. 1997, 119, 449.
31. I. Matsuo, M. Isomura, K. Ajisaka, Tetrahedron Lett.
1999, 40, 5047.
32. Y. Tatsuta, Tetrahedron Lett. 1996, 37, 2453.
33. J. Inanaga, Y. Yokoyama, T. Hanamoto, J. Chem. Soc.,
Chem. Commun. 1993, 13, 1090.
34. M. Yanase, M. Funabashi,J. Carbohydr. Chem.2000, 19, 53.
35. W. Biltz, G. F. Huettig, Z. Anorg. Allg. Chem. 1921,
119, 117.
36. G. Bartoli, G. D. Antonio, R. Giovannini, S. Giuli,
S. Lanari, M. Paoletti, E. Marcantoni, J. Org. Chem.
2008, 73, 1919.
9. S.-S. Weng, Y.-D. Lin, C.-T. Chen, Org. Lett. 2006,
8, 5633.
10. R. Geurtsen, D. S. Holmes, G.-J. Boons, J. Org. Chem.
1997, 62, 8145.
37. W. C. Schumb, E. L. Gamble, M. B. Danus, J. Am.
Chem. Soc. 1949, 71, 3225.
11. K. P. R. Kartha, R. A. Field, J. Carbohydr. Chem. 1998,
17, 693.
38. T. Ren, G. Zhang, D. Liu, Tetrahedron Lett. 2001,
42, 1007.
12. B. Rajanikanth, R. Seshadri, Tetrahedron Lett. 1987,
28, 2995.
39. S. N. Khan, A. Kim, R. H. Grubbs, Y.-U. Kwon, Org.
Lett. 2012, 14, 2952.
13. V. Kumar, N. Taxak, R. Jangir, P. V. Bharatam,
K. P. Ravindranathan Kartha, J. Org. Chem. 2014,
79, 3429.
40. S. Dumbre, A. Derouaux, E. Lescrinier, A. Piette,
B. Joris, M. Terrak, P. Herdewijn, J. Am. Chem. Soc.
2012, 134, 9343.
14. S.-S. Weng, Tetrahedron Lett. 2009, 50, 6414.
15. S.-S. Weng, C.-L. Li, C.-S. Liao, T.-A. Chen, C.-C. Huang,
K.-T. Hung, J. Carbohydr. Chem. 2010, 29, 429.
16. S. Valerio, A. Iadonisi, M. Adinolfi, A. Ravida, J. Org.
Chem. 2007, 72, 6097.
17. B. Mukhopadhyay, K. P. R. Kartha, D. A. Russell,
R. A. Field, J. Org. Chem. 2004, 69, 7758.
18. R. J. Ferrier, R. H. Furneaux, Carbohydr. Res. 1980,
52, 251.
41. C.-C. Lin, T.-S. Hsu, K.-C. Lu, I.-T. Huang, J. Am.
Chem. Soc. 2000, 47, 921.
42. G.-J. Liu, X.-T. Zhang, G.-W. Xing, Chem. Commun.
2015, 51, 12803.
43. D. E. Paterson, F. K. Griffin, M.-L. Alcaraz,
R. J. K. Taylor, Eur. J. Org. Chem. 2002, 7, 1323.
44. V. Kumar, N. Taxak, R. Jangir, P. V. Bharatam,
K. P. Ravindranathan Kartha, J. Org. Chem. 2014,
79, 3427.
10
www.jccs.wiley-vch.de
© 2017 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J. Chin. Chem. Soc. 2017