One-pot synthesis of glycosyl phenylthiosulfonates from sulfinate, S and glycosyl bromides

Article abstract of DOI:10.1016/j.carres.2018.10.005

Glycosyl phenylthiosulfonates are reagents which are valuable for the S-glycosylation decoration of organic compounds and proteins. Here, one-pot multiple-component synthesis of glycosyl phenylthiosulfonates from sulfinate, sulfur powder and glycosyl bromides is reported. The reactions afford glycosyl phenylthiosulfonates in good yields under mild conditions. Further application and exploration of glycosyl phenylthiosulfonates are still on underway in our group.

Full text of DOI:10.1016/j.carres.2018.10.005

Accepted Manuscript
One-pot synthesis of glycosyl phenylthiosulfonates from sulfinate, S and glycosyl
bromides
Chunlai Feng, Jin Wang, Qiujie Tang, Zijian Zhong, Shusen Qiao, Xingyu Liu, Can
Chen, Aihua Zhou
PII:
S0008-6215(18)30549-4
https://doi.org/10.1016/j.carres.2018.10.005
CAR 7615
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 22 September 2018
Revised Date: 18 October 2018
Accepted Date: 18 October 2018
Please cite this article as: C. Feng, J. Wang, Q. Tang, Z. Zhong, S. Qiao, X. Liu, C. Chen, A. Zhou, One-
pot synthesis of glycosyl phenylthiosulfonates from sulfinate, S and glycosyl bromides, Carbohydrate
Research (2018), doi: https://doi.org/10.1016/j.carres.2018.10.005.
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ACCEPTED MANUSCRIPT
Graphic Abstract

ACCEPTED MANUSCRIPT
Carbohydrate Research 468 (2018) 64–68
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
One-pot Synthesis of Glycosyl Phenylthiosulfonates from Sulfinate，S and Glycosyl
Bromides
a
a
a
a
a
a
a
Chunlai Feng, Jin Wang, Qiujie Tang, Zijian Zhong, Shusen Qiao, Xingyu Liu, Can Chen, Aihua
Zhou*a
a.PharmacyꢀSchool,ꢀJiangsuꢀUniversity,ꢀXuefuꢀRoadꢀ301,ꢀZhenjiangꢀcity,ꢀJiangsu,ꢀChinaꢀ212013.E-mail:ꢀahz@ujs.edu.cn.ꢀ
ꢀ
ꢀ
ꢀ
A B S T R A C T
A R T I C L E I N F O
Glycosyl phenylthiosulfonates are reagents which are valuable for the S-glycosylation decoration of organic
compounds and proteins. Here, one-pot multiple-component synthesis of glycosyl phenylthiosulfonates from
sulfinate, sulfur powder and glycosyl bromides is reported. The reactions afford glycosyl phenylthiosulfonates in good
yields under mild conditions. Further application and exploration of glycosyl phenylthiosulfonates are still on
underway in our group.
Keywords:ꢀꢀ
Thiosulfonate
Glycosylation
Sulfur
Sodium benzene sulfinate
Sugar
Disulfide
biological properties.[11] Thus, any synthetic methods or reagents for
conveniently attaching S-glycoside residues to drugs or proteins are pretty
useful to medicinal chemists (Fig. 1). Compared with other reported S-
1
.
Introduction
'
Thiosulfonates which possess R-SSO
2
-R(R, R'= Alkyl, Ar) structures
glycosylation methods, the use of glycosyl phenylthiosulfonates as S-
glycosylation reagent is more conveniennt and less odorless, and this S-
glycosylation reaction can be carried out at room temperature which is also
critical for generating S-glycosylation derivatives of some proteins.[12]
Therefore, new synthetic method of using glycosyl phenylthiosulfonate as
S-glycosylation agent is valued in drug discovery.[13]
have wide applications in organic synthesis and industry[1] Their strong
sulfenylating power has been extensively utilized in organic syntheses for
making sulfides and disulfides.[2] Thiosulfonates also have shown
biological activities because they can block the normal metabolism of the
microorganisms by sulfenylation of the enzyme’s thiol groups with SR
(
R= alkyl, aryl).[3] Normally, thiosulfonates are made by reacting
R′SO Na,[4] R′SO Cl,[5] R′SO NHNH [6]or R′SSR′[7] with thiols or
disulfides (Scheme 1).
2
2
2
2
In recent years, with the rapid development of sugar chemistry in the
field of biochemistry, the synthesis of glycosides has received more and
more attention from chemists.[8] Glycosyl phenylthiosulfonate are special
Fig. 1. Decoration of protein with glycosyl phenylthiosulfonate
'
thiosulfonates in which
monosaccharides. Like
R
(R-SSO
2
-R) is replaced by different
2
Despite there is one report of using R′SO Na, S and RX to make
normal
thiosulfonates,
glycosyl
thiosulfonates in literature,[14] but RX reagents used were alkyl halides and
reactions had to undergo two seperate steps in order to generate
thiosulfonates. Instead of using alkyl halides, we have improved the
reaction by using acetylated glycosyl bromides and combined the two
seperate reactions into a one-pot multiple-component reaction, our reactions
are carried out under mild reaction conditions without any toxic additives or
metal catalysts invovled, additionally, the yields of products are high.
phenylthiosulfonate are also good reagents for chemically connecting S-
sugar residues with functional groups of organic compounds and
proteins,[9] this process can be called S-glycosylation. Although S-
glycosylation is not as common as O-glycosylation, many examples of the
decoration of oranic compounds and proteins with S-glycoside residues
exist in the nature.[10] Compared with O-glycosides, S-glycosides are
less susceptible to acid and enzymatic hydrolysis. They have different
conformational preferences than O-glycosides, which can influence their
∗
Corresponding author.
E-mailꢀaddress:ꢀahz@ujs.edu.cn (A. Zhou).
https://doi.org/10.1016/j.carres.2018.08.013
Received
0
008-6215/ © 2018 Elsevier Ltd. All rights reserved.

ACCEPTED MANUSCRIPT
Table 2. Synthesis of glycosyl phenylthiosulfonates using different
a
sodium arene sulfinates, S powder and glycosyl bromides
Scheme 1. Previous research and our work
Results and discussion
2.
Screening to find a suitable reaction conditions for making glycosyl
phenylthiosulfonates began with using sodium benzene sulfinate 1a and S
powder as representative reactants, and acetobromo-α-D-glucose 2a was
selected as the representative sugar part. Based on the literature and our
previous research results,[14] different additives and solvents were
screened at various temperatures. The experimental results are listed in
Table 1.
Table 1
Optimization of reaction conditions.
Temp
(oC)
Yield of
Entry
Additive
Solvent
DMF
3a (%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
Bu
Bu
Bu
Bu
---
---
---
---
---
---
---
---
---
---
4
4
4
4
NBr
NI
50
0
50
70
90
25
70
70
25
70
70
70
70
70
90
DMF
DMF
0
NI
0
NI
CH
3
CN
7
H
H
H
2
2
2
O
0
O/THF (1:1)
0
O/CH
CN
3
CN (1:1)
0
CH
3
0
DMSO
0
0
Dioxane
5
1
CH
CH
3
CN
CN
62
83
0
2b
3
3
DCE
CH CN
[a] Reaction conditions: sodium arene sulfinate (2.0 equiv.), S (2 equiv.),
glycosyl bromide 2 (1.0 equiv.), additive (0.2 equiv.), solvent (0.5 mL),
4
3
35
2
reaction time 2 h. Isolated yields are based on reactant 2, under N .
a
Reaction conditions: sodium benzene sulfinate (2.0 equiv.), S (2 equiv.),
acetobromo-D-glucose 2a (1.0 equiv.), additive (0.2 equiv.), solvent (0.5 mL),
o
3
a
(entry 4). Using water as the solvent at 25 C didn't produce any 3a
reaction time 2 h. Isolated yields are based on reactant 2a.
b
(entry 5). Changing solvent from H
2
O to H
2
O/THF(1:1) or H
2
O/CH
3
CN
2
Under N .
o
(
1:1) at 70 C also didn't afford any 3a (entries 6, 7). When CH
3
CN was
o
solely employed, no 3a was generated at 25 C (entry 8). Replacing CH
3
CN
4
The screening started with using phase transfer catalyst Bu NBr as an
o
o
with DMSO as the solvent at 70 C also didn't lead to any 3a (entry 9).
additive in DMF at 50 C. This reaction failed to give expected product
Employing dioxane gave a 5% yield of 3a (entry 10). Using CH
3
CN as the
3
a
(Table 1, entry 1). Replacing Bu
4 4
NBr with Bu NI as a phase transfer
o
solvent at 70 C generated 3a in 62% (entry 11). When this same reaction
catalyst also didn’t give any product (entry 2). Increasing the reaction
o
was performed under N , it afforded 83% of 3a (entry 12). Using DCE as
temperature to 70 C still failed to give any 3a (entry 3). Raising the
2
o
o
3
the solvent didn't give 3a (entry 13). Using CH CN as the solvent at 90 C
temperature to 90 C in CH
3
CN, the reaction only generated a 7% yield of

ACCEPTED MANUSCRIPT
under air produced 35% of 3a (entry 14). So the optimized reaction Flash column chromatography was performed on silica gel (200-300 mesh).
conditions selected using both S and an acetobromo-α-D-glucose 2a to generate All reactions were monitored by TLC analysis. Deuterated solvents were
1
13
glycosyl phenylthiosulfonates are: the sodium benzene sulfinate (2.0 equiv.), purchased from Cambridge Isotope laboratories. H and C NMR spectra
o
S (2 equiv.), acetobromo-D-glucose 2a (1.0 equiv.) in CH
3
CN at 70 C under were recorded on a Bruker DRX-400 spectrometer operating at 400 MHz and
100 MHz respectively. HRMS spectrometry (LC-HRMS) was recorded on a
N
2
for 2h.
Under the optimum conditions defined above, different sodium aromatic LXQ Spectrometer (Thermo Scientific) operating in the ESI-TOF mode
sulfinates with electron-withdrawing (-F, -Cl and -Br) and electron-donating (MeOH as a solvent).
substitutes (-CH , -OCH ) and various acetated D- or L-glycosyl bromides
including acetyl-D-glucopyranosyl bromide, acetyl-D-arabinopyranosyl
3
3
General procedure for the synthesis of compounds 3.
2R,3R,4S,5R)-2-(Acetoxymethyl)-6-bromotetrahydro-2H-pyran-3,4,5-triyl
(
(
bromide, acetyl-L-arabinopyranosyl bromide, acetyl-D-galactopyranosyl
bromide, acetyl-D-xylopyranosyl bromide and acetyl-L-xylopyranosyl bromide)
were selected and tried in these reactions. Most reactions of sodium arene
sulfinates with different glycosyl bromides proceeded well, giving good yields
of glycosyl phenylthiosulfonates. The isolated yields of most reactions ranged
from 69% to 90%, giving different ratios of α/β anomers (shown in Table 2). It
was easily found that β-diastereoisomers were more favorable anomer products.
But glycosyl bromides without any functions on the 2-position failed to give
any expected products. Different ratios of α/β anomers of glycosyl
phenylthiosulfonates were determined by H-NMR spectra. The resultant
triacetate 2a (0.5 mmol, 1.0 equiv.), S (2.0 equiv.) and sodium benzene
sulfinate (2.0 equiv.) were added to round-bottom flasks with acetonitrile (0.5
0
mL) in it. Then the mixture was stirred at 70 C. After 2 h, the reaction was
cooled down to room temperature. The reaction mixture was quenched with
2 4
water, then extracted with ethyl acetate, dried over anhydrous Na SO and
concentrated under vacuum. The residue was purified by silica gel flash
chromatography (petroleum ether : EtOAc = 5: 1) to give product 3a as a
yellow oil in 83% yield. The same procedure was applied to the production of
compound 3b-n
.
glycosyl phenylthiosulfonate reacted with p-methylbezenethiol in DMF at
General procedure for the synthesis of compounds 4a.
,3,4,6-Tetra-O-acetyl- -D-glucopyranosyl phenylthiosulfonate
mmol, 1.0 equiv.), -methylbezenethiol (1.5 equiv.), Triethylamine (1.5
room temperature, generating disulfide 4a in a good yield. Its NMR
2
β
(3a) (0.5
spectrum matched well the one previously reported in the literature.
p
equiv.) were added to DMF (1.0 mL) in round-bottom flasks under nitrogen
atmosphere. The mixture was stirred at room temperature for 24 h. The
reaction mixture was quenched with water, then extracted with ethyl acetate,
dried over anhydrous Na
2 4
SO and concentrated under vacuum. The residue
Scheme 2. Reaction with PhSH
was purified by silica gel flash chromatography (petroleum ether : EtOAc =
1
0:1) to give product 4a as a yellow oil in 76% yield.
Based on previous reports,[14] a simple but plausible mechanism is
proposed in Scheme 3, in which sodium benzene sulfinate reacted with S
first to give sodium benzenesulfonothioate intermediate, then it further
2
,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl phenylthiosulfonate (3a) [3b]
Following the general procedure, isolated yield (83%) as a colorless oil; IR:
-1
1
2
945, 2361, 1750, 1375, 1331, 1228, 1146 cm ; H-NMR (CDCl
3
, 400
reacted with the glycosyl bromide to afford glycosyl phenylthiosulfonate
.
MHz):δ 8.05 – 7.86 (m, 2H), 7.76 – 7.44 (m, 3H), 5.32 – 5.18 (m, 2H), 5.11 –
4
.96 (m, 2H), 4.11 (dd,
J
= 12.5, 4.5 Hz, 1H), 3.91 (dd,
J
= 12.5, 2.4 Hz, 1H),
, 100 MHz)
1
3
3
.79 – 3.69 (m, 1H), 2.16 – 1.96 (m, 12H); C-NMR (CDCl
3
：δ
1
7
70.35, 169.83, 169.29, 169.25, 145.85, 134.01, 129.23, 126.97, 86.65,
6.37, 73.42, 68.69, 67.72, 61.50, 20.66, 20.49,20.44.MS (ESI-TOF) m/z
+
+
2
calculated for C20H24NaO11S 527.06(M+Na) , found 527.42.
2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl p-chlorophenylthiosulfonate (3b)
Scheme 3. Possible reaction mechanism
Following the general procedure, isolated yield (74%) as a colorless oil; IR:
-1
1
3
7
4
J
094, 2948, 1755, 1370, 1230, 1149 cm ; H-NMR (CDCl
.89 (d, = 8.7 Hz, 2H), 7.52 (d, = 8.7 Hz, 2H), 5.35 – 5.21 (m, 2H), 5.17 –
.98 (m, 2H), 4.18 – 4.07 (m, 1H), 4.01 (dd, = 12.5, 2.4 Hz, 1H), 3.77 (ddd,
= 10.2, 4.6, 2.4 Hz, 1H), 2.13 – 1.97 (m, 12H); C-NMR (CDCl
δ170.51, 170.26, 169.79, 169.28, 169.26, 144.29, 140.66, 129.58,
3
, 400 MHz): δ
J
J
J
3.
Conclusion
13
3
, 100
MHz)
：
1
6
29.49, 129.46, 128.47, 86.64, 73.42, 73.33, 68.65, 67.79, 67.74, 61.57,
1.49, 20.64, 20.56, 20.51, 20.48, 20.47, 20.45. MS (ESI-TOF) m/z
In summary, we reported a convenient one-pot and multiple-component
+
+
synthesis of glycosyl phenylthiosulfonates by using different sulfinates, S calculated for C20
2
H23ClNaO11S 561.02(M+Na) , found 561.50.
powder and glycosyl bromides as starting materials. Most reactions afforded
2
(
,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl
3c)
Following the general procedure, isolated yield (71%) as a colorless oil; IR:
p-fluorophenylthiosulfonate
good yields of glycosyl phenylthiosulfonates under mild conditions. Glycosyl
phenylthiosulfonates have been proved to be valuable reagents for the S-
-
1
glycosylation decoration of organic compounds and proteins. Further study to 2953, 1756, 1588, 1493, 1228, 1145 cm ; 1H-NMR (CDCl
3
, 400 MHz): δ
= 9.0, 8.1 Hz, 2H), 5.33 – 5.20 (m,
H), 5.15 – 4.96 (m, 2H), 4.14 – 4.07 (m, 1H), 4.00 (dd, = 12.6, 2.5 Hz,
H), 3.81 – 3.71 (m, 1H), 2.11 – 1.98 (m, 12H); C-NMR (CDCl , 100 MHz)
δ 170.25, 169.79, 169.28, 169.26, 131.06, 130.96, 130.03, 129.93, 116.60,
16.37, 86.62, 73.42, 73.32, 68.64, 67.75, 61.50, 20.62, 20.49, 20.47, 20.45.
7
2
1
：
1
.97 (dd, J = 9.0, 4.9 Hz, 2H), 7.22 (dd, J
expand the application scope of glycosyl phenylthiosulfonates are still
underway in our group.
J
13
3
4. Experimental
+
+
2
MS (ESI-TOF) m/z calculated for C20H23FNaO11S 545.05 (M+Na) , found
5
45.46.
General: All reactions were carried out in sealed tubes; stirring was
achieved with an oven-dried magnetic stirring bar. Solvents were purified 2,3,4-Tri-O-acetyl-β-D-arabinopyranosyl phenylthiosulfonate (3d)
Following the general procedure, isolated yield (80%) as a colorless oil; IR:
by standard methods unless otherwise noted. Commercially available
reagents were purchased from Aladdin Company in China and used
throughout without further purification other than those detailed below. (d,
-1
1
2
970, 2361, 1752, 1372, 1331, 1221, 1147 cm ; H-NMR (CDCl
MHz): δ 8.09 – 7.83 (m, 2H), 7.75 – 7.47 (m, 3H), 5.45 – 5.37 (m, 1H), 5.28
= 10.0 Hz, 1H), 5.20 (td, = 10.0, 3.3 Hz, 1H), 5.12 (dd, = 9.8, 3.3 Hz,
3
, 400
J
J
J

ACCEPTED MANUSCRIPT
1
3
1
H), 4.03 – 3.89 (m, 2H), 3.88 – 3.77 (m, 1H), 2.12 – 1.92 (m, 12H); C- 114.32, 114.24, 86.42, 68.64, 68.21, 65.83, 55.83,55.77, 20.76, 20.70, 20.66,
+ +
3
NMR (CDCl , 100 MHz)：
2
δ 170.16, 169.94, 169.69, 169.54, 145.93, 20.62. MS (ESI-TOF) m/z calculated for C18H22NaO10S 485.05 (M+Na) ,
33.98, 129.29, 129.22, 127.95, 126.98, 87.25, 74.98, 71.46, 66.83, 65.87, found 485.43.
1
6
0.77, 20.64, 20.56, 20.54, 20.51, 20.47, 20.45. MS (ESI-TOF) m/z
+
+
2
calculated for C20H24NaO11S 527.06 (M+Na) , found 527.38.
2
(
,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl p-chlorophenylthiosulfonate
3k)
,3,4-Tri-O-acetyl-β-D-arabinopyranosyl p-methoxyphenylthiosulfonate Following the general procedure, isolated yield (78%) as a colorless oil; IR:
2
-
1 1
(
3e)
2979, 1752, 1578, 1372, 1221, 1148 cm ; H-NMR (CDCl , 400 MHz): δ
= 8.7 Hz, 2H), 7.49 (d, = 8.7 Hz, 2H), 5.62 (d, = 4.9 Hz, 1H),
, 400 MHz):δ 5.26 – 5.15 (m, 2H), 5.08 (dd, = 5.9, 4.9 Hz, 1H), 3.78 (dd, J = 12.1, 6.9 Hz,
3
Following the general procedure, isolated yield (77%) as a colorless oil; IR: 7.84 (d,
J
J
J
-1
1
2
7
5
3
3
1
1
6
966, 1751, 1372, 1334, 1220, 1145 cm ; H-NMR (CDCl
3
J
1
3
.81 (d,
.27 (d,
J
J
= 8.4 Hz, 2H), 7.44 – 7.28 (m, 2H), 5.42 (dd,
J
= 3.4, 1.0 Hz, 1H), 1H), 3.64 – 3.51 (m, 1H), 2.11 – 1.98 (m, 9H); C-NMR (CDCl
= 9.6,
δ 169.65, 169.12, 169.03, 144.24, 140.39, 129.49, 129.45, 128.49, 86.62,
= 8.6 Hz, 68.66, 67.94, 65.60, 62.10, 20.64, 20.61, 20.58. MS (ESI-TOF) m/z
3
, 100 MHz)
= 10.1 Hz, 1H), 5.20 (td, = 10.1, 5.0 Hz, 1H), 5.11 (dd,
J
J
：
.3 Hz, 1H), 4.01 – 3.91 (m, 2H), 3.90 – 3.80 (m, 1H), 2.45 (d,
H), 2.19 – 1.91 (m, 12H); C-NMR (CDCl
J
1
3
+
+
：
9 2
δ170.17, 169.94, calculated for C17H19ClNaO S 489.00 (M+Na) , found 489.38.
3
, 100 MHz)
69.71, 169.53, 145.80, 145.25, 143.14, 139.52, 129.86, 129.77, 128.04,
27.07, 89.34, 87.21, 75.08, 74.97, 71.50, 67.52, 66.95, 66.85, 65.90,
1.06,60.77, 60.32, 21.71, 21.63, 20.62, 20.55, 20.52, 20.48, 20.45. MS
2
,3,4-Tri-O-acetyl-β-L-xylopyranosyl phenylthiosulfonate (3l)
Following the general procedure, isolated yield (65%) as a colorless oil; IR:
+
+
-1
1
2
(ESI-TOF) m/z calculated for C21H26NaO11S 541.08 (M+Na) , found
2
7
J
974, 1752, 1572, 1372, 1220, 1146 cm ; H-NMR (CDCl
.87 – 7.77 (m, 2H), 7.75 – 7.65 (m, 2H), 5.66 (d, = 4.8 Hz, 1H), 5.23 (ddd,
= 9.5, 7.5, 3.3 Hz, 2H), 5.12 (dd, = 5.9, 4.8 Hz, 1H), 3.82 (dd, = 12.1,
, 100
δ 169.71, 169.14, 169.06, 144.80, 132.47, 129.09, 128.51, 86.66,
, 400 MHz):δ 68.71, 67.92, 65.55, 62.00, 20.69, 20.67, 20.63. MS (ESI-TOF) m/z
3
, 400 MHz): δ
5
41.47.
J
J
J
1
3
2
,3,4-Tri-O-acetyl-β-L-arabinopyranosyl p-chlorophenylthiosulfonate (3f)
7.1 Hz, 1H), 3.68 – 3.53 (m, 1H), 2.16 – 2.02 (m, 9H); C-NMR (CDCl
3
Following the general procedure, isolated yield (73%) as a colorless oil; IR: MHz)
：
-1
1
2
7
968, 1577, 1593, 1371, 1228, 1146 cm ; H-NMR (CDCl
.85 (d, = 9.0 Hz, 2H), 6.99 (s, 2H), 5.40 (t, = 3.9 Hz, 1H), 5.28 – 5.14 calculated for C17
= 9.5, 3.3 Hz, 1H), 4.18 – 3.99 (m, 1H), 4.00 – 3.91 (m,
3
+
+
J
J
9 2
H19BrNaO S 532.95 (M+Na) , found 533.32.
(
2
m, 2H), 5.10 (dd,
H), 3.88 (d, = 7.3 Hz, 3H), 2.13 – 1.95 (m, 12H); C-NMR (CDCl
MHz) δ 170.33, 170.21, 169.98, 169.77, 169.74, 169.56, 164.35, 163.92,
37.57, 130.39, 129.44, 114.37, 114.27, 87.14, 75.07, 74.91, 71.49, 66.87,
5.90, 60.81, 55.84, 55.81, 20.63, 20.58, 20.53, 20.46. MS (ESI-TOF) m/z
J
1
3
J
3
, 100
2,3,4-Tri-O-acetyl-β-L-xylopyranosyl p-tolylthiosulfonate (3m)
：
Following the general procedure, isolated yield (73%) as a colorless oil; IR:
-
1
1
1
6
2
8
=
(
923, 2852, 1746, 1373, 1211, 1144 cm ; H-NMR (CDCl
.11 – 7.82 (m, 2H), 7.76 – 7.43 (m, 3H), 5.68 (d, = 5.2 Hz, 1H), 5.10 (t,
5.8 Hz, 1H), 4.90 (t, = 5.4 Hz, 1H), 4.73 (td, = 5.6, 3.6 Hz, 1H), 3.97
dd, = 12.7, 3.6 Hz, 1H), 3.43 (dd,
3
, 400 MHz):δ
J
J
J
+
+
2
calculated for C21H26NaO12S 557.07 (M+Na) , found 557.48.
J
J
J
= 12.7, 5.4 Hz, 1H), 2.19 – 1.90 (m,
δ 169.60, 169.09, 168.80, 145.77,
1
3
2
(
,3,4-Tri-O-acetyl-β-L-arabinopyranosyl
3g)
Following the general procedure, isolated yield (67%) as a colorless oil; IR: 20.58. MS (ESI-TOF) m/z calculated for C17
p-bromophenylthiosulfonate 9H); C-NMR (CDCl
3
, 100 MHz)
：
133.90, 129.18, 127.04, 86.54, 68.21, 68.17, 66.86, 62.70, 20.73, 20.63,
+
+
H
9 2
20NaO S 455.04 (M+Na) ,
-
1
1
2
7
3
964, 1752, 1589, 1493, 1221, 1145 cm ; H-NMR (CDCl
.98 (dd, = 9.0, 4.9 Hz, 2H), 7.23 (dd, = 9.0, 8.1 Hz, 2H), 5.43 (dd,
.4, 0.9 Hz, 1H), 5.31 (d, = 10.1 Hz, 1H), 5.21 (t, = 9.9 Hz, 1H), 5.13
= 9.8, 3.3 Hz, 1H), 4.06 – 3.96 (m, 2H), 3.94 – 3.84 (m, 1H), 2.12 –
3
, 400 MHz): δ found 455.39.
J
J
J =
J
J
2,3,4-Tri-O-acetyl-β-D-xylopyranosyl phenylthiosulfonate (3n)
(dd,
J
Following the general procedure, isolated yield (76%) as a colorless oil; IR:
1
3
-
1
1
2
1
8
3
.03 (m, 9H), 1.97 (s, 3H); C-NMR (CDCl , 100 MHz)：δ 170.17, 169.92,
3
7
435, 1763, 1748, 1218, 1140, 1067 cm ; H-NMR (CDCl
.99 – 7.67 (m, 2H), 7.31 (d, = 8.1 Hz, 2H), 5.63 (d, = 5.3 Hz, 1H), 5.08
= 5.5 Hz, 1H), 4.75 – 4.64 (m, 1H), 3.96 (dd,
= 12.7, 5.5 Hz, 1H), 2.42 (s, 3H), 2.15 – 1.95
, 100 MHz) δ 169.61, 169.09, 168.82,145.09,
3
, 400 MHz):δ
69.69, 169.56, 166.94, 164.39, 142.02, 130.07, 129.97, 116.58, 116.35,
7.30, 75.14, 71.42, 66.88, 65.82, 60.94, 60.33,20.62,20.57, 20.51, 20.44.
J
J
(t, J = 5.8 Hz, 1H), 4.88 (t,
J
J =
+
+
2
MS (ESI-TOF) m/z calculated for C20H23FNaO11S 545.05 (M+Na) , found
5
1
2.7, 3.6 Hz, 1H), 3.42 (dd,
J
45.43.
13
(m, 9H); C-NMR (CDCl
3
：
1
42.97, 129.74, 127.08, 86.46, 68.29, 68.19,66.91, 62.77, 21.65, 20.72,
+
2
,3,4-Tri-O-acetyl-β-L-arabinopyranosyl
2,3-dihydrobenzofuranylthio- 20.61, 20.57. MS (ESI-TOF) m/z calculated for C18
H
22NaO
9
S
2
469.06
+
sulfonate (3h)
Following the general procedure, isolated yield (72%) as a colorless oil; IR:
(M+Na) , found 469.45.
-
1
1
2
7
1
3
1
1
2
966, 1752, 1581, 1371, 1222, 1149 cm ; H-NMR (CDCl
.89 (d, = 8.7 Hz, 2H), 7.51 (d, = 8.8 Hz, 2H), 5.42 (dd,
H), 5.31 (d, = 10.0 Hz, 1H), 5.20 (t, = 9.9 Hz, 1H), 5.13 (dd,
.3 Hz, 1H), 4.06 – 3.96 (m, 2H), 3.94 – 3.82 (m, 1H), 2.11 – 1.95 (m,
2H); C-NMR (CDCl
44.38, 140.59, 129.47, 128.51, 87.28, 75.16, 71.38, 66.90, 65.80, 60.99,
3
, 400 MHz): δ
= 3.2, 0.9 Hz,
= 9.8,
4
-Tolylphenyl-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) disulfide (4a)
J
J
J
[16]
J
J
J
isolated yield (72%) as a colorless oil; 1H-NMR (CDCl3, 400 MHz): δ 7.51
(d, J = 8.2 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 5.42 – 5.21 (m, 2H), 5.21 – 5.03
1
3
3
, 100 MHz)：δ 170.18, 169.92, 169.68, 169.57,
(
1
m, 1H), 4.74 – 4.50 (m, 1H), 4.20 (dd, J = 12.4, 4.6 Hz, 1H), 4.12 (dd, J =
2.4, 2.3 Hz, 1H), 3.76 (ddd, J = 10.0, 4.6, 2.4 Hz, 1H), 2.34 (s, 3H), 2.04 (d,
J = 4.5 Hz, 12H). MS (ESI-TOF) m/z calculated for C21H26NaO9S2+
0.65,
20.57,
20.52,20.45.MS(ESI-TOF)
561.02 (M+Na) , found 561.50.
m/z
calculated
for
+
2
+
C
20
H
23ClNaO11
S
5
09.09 (M+Na)+, found 509.31.
2
(
,3,4,6-Tetra-O-acetyl-β-D-galactopyranosyl p-fluorophenylthiosulfonate
3i)
Following the general procedure, isolated yield (69%) as a colorless oil; IR:
Acknowledgement
-1
1
This investigation was generously supported by the funding
(1281290006) provided by Jiangsu University in China.
2
7
5
1
1
1
2
C
973, 1749, 1367, 1227, 1151, 1069 cm ; H-NMR (CDCl
.87 – 7.79 (m, 2H), 7.70 (d, J = 8.7 Hz, 2H), 5.44 (dd,
.31 (d,
H), 4.08 – 3.96 (m, 2H), 3.90 (dd,
2H); C-NMR (CDCl
44.94, 132.48, 129.23, 128.52, 87.34, 75.22,71.43, 66.87, 65.81, 60.97,
0.67, 20.58, 20.54, 20.46. MS (ESI-TOF) m/z calculated for
3
, 400 MHz):δ
= 3.4, 1.1 Hz, 1H),
= 9.9 Hz, 1H), 5.13 (dd, = 9.7, 3.3 Hz,
= 10.1, 5.2 Hz, 1H), 2.13 – 1.98 (m,
δ 170.19, 169.92, 169.69, 169.56,
J
J
= 10.2 Hz, 1H), 5.22 (t,
J
J
J
：
1
3
3
, 100 MHz)
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2

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Highlights:
One-pot Synthesis of Glycosyl Phenylthiosulfonates from Sulfinate，S and Glycosyl Bromides