A facile and efficient method for the one-pot synthesis of per-O-acetylated thioglycosides from unprotected sugars

Article abstract of DOI:10.1080/07328303.2012.673669

An efficient, convenient protocol for the preparation of per-O-acetylated p-tolylthio glycosides is described. Treatment of various unprotected sugars, including 2-deoxy-2-amino sugars, sialic acid, lactose, and maltose, with acetic anhydride using SnCl₄ as a catalyst, and subsequently with p-tolylthiol, furnished the corresponding thioglycosides in 71%-90% yield under solvent-free conditions.

Full text of DOI:10.1080/07328303.2012.673669

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A Facile and Efficient Method for the
One-Pot Synthesis of Per-O-acetylated
Thioglycosides from Unprotected Sugars
Shiqiang Yan a , Ning Ding b , Wei Zhang b , Peng Wang a , Yingxia Li b
& Ming Li a
a Key Laboratory of Marine Drugs, Ministry of Education, Ocean
University of China, Qingdao, 266003, China
b School of Pharmacy, Fudan University, Shanghai, 201203, China
Version of record first published: 30 Aug 2012
To cite this article: Shiqiang Yan, Ning Ding, Wei Zhang, Peng Wang, Yingxia Li & Ming Li (2012):
A Facile and Efficient Method for the One-Pot Synthesis of Per-O-acetylated Thioglycosides from
Unprotected Sugars, Journal of Carbohydrate Chemistry, 31:7, 571-583
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Journal of Carbohydrate Chemistry, 31:571–583, 2012
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C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2012.673669
A Facile and Efficient Method
for the One-Pot Synthesis of
Per-O-acetylated
Thioglycosides from
Unprotected Sugars
Shiqiang Yan,1 Ning Ding,2 Wei Zhang,2 Peng Wang,1
Yingxia Li,2 and Ming Li1
1Key Laboratory of Marine Drugs, Ministry of Education, Ocean University of China,
Qingdao 266003, China
2School of Pharmacy, Fudan University, Shanghai 201203, China
An efficient, convenient protocol for the preparation of per-O-acetylated p-tolylthio gly-
cosides is described. Treatment of various unprotected sugars, including 2-deoxy-2-
amino sugars, sialic acid, lactose, and maltose, with acetic anhydride using SnCl4 as
a catalyst, and subsequently with p-tolylthiol, furnished the corresponding thioglyco-
sides in 71%–90% yield under solvent-free conditions.
Keywords Acetylation; Thioglycosides; One-pot synthesis; Unprotected sugars; SnCl4
INTRODUCTION
The rapid development of glycobiology reveals that oligosaccharides play
important roles in a wide array of biological processes such as cell–cell
interaction, cell–cell adhesion, bacterial attachment, viral infection, and
substrate–receptor recognition.[1] Therefore, highly efficient and practical
methodologies for the synthesis of oligosaccharides employing thioglycosides
as glycosyl donors have attracted considerable interest, because thioglycosides
enable new synthetic strategies such as armed–disarmed glycosylation,[2] or-
thogonal glycosylation,[3] sequential iterative glycosylation,[4] reactivity-based
Received December 29, 2011; accepted December 5, 2012.
Address correspondence to Yingxia Li, School of Pharmacy, Fudan University,
Shanghai 201203, China. E-mail: liyx417@fudan.edu.cn; and Ming Li, Key Laboratory
of Marine Drugs, Ministry of Education, Ocean University of China, Qingdao 266003,
China. E-mail: lmsnouc@ouc.edu.cn
571

S. Yan et al.
572
one-pot glycosylation,[5] and automated solid-phase oligosaccharide synthe-
sis.[6]
In practice, per-O-acetylated thioglycosides are valuable building blocks
for the synthesis of carbohydrate derivatives[7] due to their unique character-
istics. Not only could they be activated as glycosyl donors under particular
conditions to take part in glycosylation, but also they have the capability
to survive various reaction conditions to make complex building blocks
or transform to other glycosyl donors. Conventionally, the preparation of
per-O-acetylated thioglycosides is achieved by a two-step sequence involving
acetylation of free sugar with an excess of acetic anhydride in pyridine,
followed by the displacement of the anomeric acetate group by a thiol in
the presence of a Lewis acid. Recently, two-step one-pot and three-step
one-pot strategies for the preparation of per-O-acetylated thioglycosides from
unprotected reducing sugars have been developed with catalyst systems
including Cu(OTf)2/BF3·OEt2,[9] La(OTf)3/BF3·OEt2,[10] LiClO4/ BF3·OEt2,[11]
TsOH/ BF3·OEt2,[12] simple BF3·OEt2,[13] I2/I2-Al,[14] I2/I2-HMDS,[15] and
HBr-AcOH/TBAHS-NaHCO3.[16] However, most of the existing methods have
pitfalls such as being time-consuming,[9,11,12] requiring solvent removal before
thioglycosidation,[10,12] and having a limited substrate scope.[9,14]
Tin tetrachloride (SnCl4) has been extensively used as a Lewis acid in
organic synthesis.[17] Recently, SnCl4 supported on silica gel has been docu-
mented as a catalyst for the conversion of aldehydes into their corresponding
acylals with an excess of acetic anhydride.[18] Meanwhile, it is well known that
SnCl4 is able to promote glycosidation of peracetylated sugars with thiol and
alcohols.[19] Inspired by these results, we envisioned that the use of a stoichio-
metric quantity of acetic anhydride in the presence of SnCl4 followed by the
addition of a thiol would result in a one-pot strategy for the preparation of per-
O-acetylated thioglycosides. Herein, we describe our findings along this line.
RESULTS AND DISCUSSION
To the best of our knowledge, SnCl4-promoted acetylation of free sugars with
stoichiometric acetic anhydride followed by subsequent glycosylation with thiol
in a one-pot manner has not been explored. Thus, we commenced with D-
glucose for the standardization of reaction conditions. After screening various
conditions, the optimized procedure was found to be treatment of D-glucose
1a (1.0 mmol) with acetic anhydride (5.1 mmol) at rt followed by slow addi-
tion of SnCl4 (2.0 mmol) to result in an immediate exothermic reaction and
a clean solution within a few minutes. After per-O-acetylated D-glucose was
formed with the complete consumption of glucose as indicated by TLC, p-
thiocresol (1.2 equiv.) was added to the reaction mixture, with the resulting
solution being stirred for an extensive 12 h. After usual workup, the reac-
tion gave rise to the desired thioglycoside 2a in 74% yield (entry 1, Table 1).

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575

S. Yan et al.
576
When D-galactose 1b and D-mannose 1c were exposed to the reaction condi-
tions, the corresponding thioglycosides 2b and 2c were obtained in 75% and
71% yields, respectively (entries 2 and 3, Table 1). For 6-deoxy sugars includ-
ing L-rhamnose 1d and L-fucose 1e, as well as pentoses like L-arabinose 1g
and D-xylose 1f, it should be noted that 1.0 equivalent of SnCl4 enabled the
preparation of thioglycosides 2d–2g in a shorter time (1.0 h) in good to ex-
cellent yield of 78%–90% (Entry 4–7, Table 1), which might be ascribed to
the higher reactivity of deoxysugars and pentoses compared with the common
sugars. Moreover, we further extended the substrates to amino sugars, fre-
quently occurring in natural oligosaccharides,[22] which did not work well with
some of the documented catalysts.[9,14] To our delight, our protocol was well
applicable to 2-phthalimdo-2-deoxy-D-glucopyranose 1h, 2-acetamido-2-deoxy-
D-glucopyranose 1i, and 2-acetamido-2-deoxy-D-galacopyranose 1j, which af-
forded the thioglycoside 2h–2j in 83%–89% yields (entries 8–10, Table 1). It is
noteworthy that N-acetyl sialic acid methyl ester 1k could be stereoselectively
converted into β-thioglycoside 2k in 85% yield in 6 h according to our proce-
dure (entry 11, Table 1), which is a valuable glycosyl donor in carbohydrate
chemistry.[23] In addition, despite sluggish acetylation compared to monosac-
charides, D-lactose 1l and D-maltose 1m, functioning as disaccharide units
of many naturally occurring glycoconjugates and polysaccarides with α- and
β-glycosidic bonds, respectively, were subjected to our protocol, leading to thio-
glycosides 2l and 2m in 86% and 88% yields with the original glycosidic bonds
unaffected. In most of the cases, the 1,2-trans-thioglycoside was obtained,
which is attributed to the neighboring group participation of the acetyl group
at C-2, except for L-rhamnose monohydrate, which afforded an α/β-mixture in
1
a ratio of 5/1. H NMR, 13C NMR, and MS spectra data of the thioglycosides
listed in Table 1 are identical with those in the references.
In summary, a one-pot, efficient, and convenient protocol for the prepa-
ration of per-O-acetylated p-tolylthioglycosides from free sugars was devel-
oped, making use of acetylation with stoichiometric acetic anhydride and
subsequent thioglycosidation with thiocresol mediated by SnCl4. The reac-
tion was fast, high yielding, and devoid of glycosidic bond cleavage. Given
p-tolylthioglycosides as popular glycosyl donors in carbohydrate chemistry, the
present method should find a wide application in oligosaccharide and glycocon-
jugate synthesis.
EXPERIMENTAL
General Methods
1H and 13C NMR spectra were recorded with a Bruker DPX400 spectrom-
1
eter in CDCl3 solutions. Internal references: TMS (δ 0.00 ppm for H), CDCl3

Synthesis of Per-O-acetylated Thioglycosides
577
(δ 77.00 ppm for 13C). Electrospray-ionization mass spectra (ESIMS) was per-
formed by the Fudan University. Thin-layer chromatography (TLC) was per-
formed on silica gel HF with detection by charring with 5% (v/v) H2SO4 in
MeOH or by UV detection. Column chromatography was conducted by elu-
tion of a column of silica gel (200–300 mesh) with EtOAc/petroleum ether (bp
60–90◦C) as the eluent. Solutions were concentrated at a temperature <60◦C
under diminished pressure.
Typical procedure for the synthesis of per-O-acetylated
thioglycosides
To a suspension of unprotected sugar (5.0 mmol) in Ac2O (1.02 mmol/OH)
was slowly added SnCl4 (1.15 mL, 10.0 mmol). After completion of the reac-
tion (as indicated by TLC), thiocresol (0.74 g, 6.0 mmol) was added and the
reaction mixture was allowed to stir for the appropriate time in Table 1. Then
the reaction mixture was poured into ice water and extracted with CH2Cl2.
The organic layer was washed with saturated aqueous NaHCO3 and brine and
dried over anhydrous Na2SO4, and the solids filtered off. The filtrate was con-
centrated under reduced pressure and the remains were purified by column
chromatography using hexane–EtOAc or recrystallization using EtOH to fur-
nish the pure product.
p-Tolyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside (2a)
1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J = 7.8 Hz, 2H, ArH), 7.12 (d, J =
7.8 Hz, 2H, ArH), 5.20 (t, J = 9.4 Hz, 1H, H-3), 5.02 (t, J = 9.8 Hz, 1H, H-4),
4.93 (t, J = 9.8 Hz, 1H, H-2), 4.63 (d, J = 10.2 Hz, 1H, H-1), 4.23–4.15 (m, 2H,
H-6), 3.69 (ddd, J = 2.3, 4.3, 7.4 Hz, 1H, H-5), 2.34 (s, 3H, STol-CH3), 2.09 (s,
3H, Ac), 2.08 (s, 3H, Ac), 2.01 (s, 3H, Ac), 1.98 (s, 3H, Ac); 13C NMR (100 MHz,
CDCl3) δ: 170.56, 170.17, 169.36, 169.22, 138.76, 133.79, 129.64, 127.47, 85.77,
75.68, 73.96, 69.84, 68.12, 62.07, 21.15, 20.74, 20.70, 20.57.
p-Tolyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranoside (2b)
1H NMR (400 MHz, CDCl3) δ: 7.41 (d, J = 8.3 Hz, 2H, ArH), 7.12 (d, J =
7.9 Hz, 2H, ArH), 5.40 (d, J = 3.2 Hz, 1H, H-4), 5.21 (t, J = 9.9, 10.3 Hz, 1H,
H-2), 5.03 (dd, J = 3.1, 9.9 Hz, H-3), 4.64 (d, J = 9.9 Hz, H-1), 4.18 (dd, J =
7.1, 11.4 Hz, 1H, H-6a), 4.10 (dd, J = 6.3, 11.4 Hz, H-6b), 3.90 (t, J = 6.7 Hz,
H-5), 2.34 (s, 3H, STol-CH3), 2.11 (s, 3H, Ac), 2.09 (s, 3H, Ac), 2.04 (s, 3H, Ac),
1.97 (s, 3H, Ac); 13C NMR (100 MHz, CDCl3) δ: 170.36, 170.19, 170.06, 169.42,
138.44, 133.10, 129.60, 128.57, 86.92, 74.29, 71.98, 67.23, 67.16, 61.54, 21.12,
20.83, 20.64, 20.60, 20.56.

S. Yan et al.
578
p-Tolyl 2,3,4,6-tetra-O-acetyl-1-thio-α-D-mannopyranoside (2c)
1H NMR (400 MHz, CDCl3) δ: 7.37 (d, J = 8.2 Hz, 2H, ArH), 7.12 (d, J =
8.2 Hz, 2H, ArH), 5.48 (d, J = 1.6 Hz, 1H, H-2), 5.40 (d, J = 1.2 Hz, 1H, H-
1), 5.35–5.29 (m, 2H, H-3, H-4), 4.55 (ddd, J = 2.4, 5.9, 9.8 Hz, 1H, H-5), 4.29
(dd, J = 5.8, 12.1 Hz, 1H, H-6a), 4.10 (dd, J = 2.1, 12.5 Hz, 1H, H-6b), 2.34
(s, 3H, STol-CH3), 2.14 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.06 (s, 3H, Ac), 2.01 (s,
3H, Ac); 13C NMR (100 MHz, CDCl3) δ: 170.51, 169.88, 169.77, 169.71, 138.40,
132.55, 129.89, 128.68, 85.95, 70.79, 69.32, 69.28, 66.31, 62.42, 21.07, 20.82,
20.66, 20.64, 20.59.
p-Tolyl 2,3,4-tri-O-acetyl-1-thio-α-L-rhamnopyranoside (2d)
1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J = 7.8 Hz, 2H, ArH), 7.11 (d, J =
8.2 Hz, 2H, ArH), 5.47 (dd, J = 1.6, 3.1 Hz, 1H, H-2), 5.31 (d, J = 1.2 Hz, 1H,
H-1), 5.28 (dd, J = 3.2, 9.8 Hz, 1H, H-3), 5.12 (t, J = 9.9 Hz, 1H, H-4), 4.35
(m, 1H, H-5), 2.31 (s, 3H, STol-CH3), 2.12 (s, 3H, Ac), 2.06 (s, 3H, Ac), 1.99 (s,
3H, Ac), 1.23 (d, J = 6.2 Hz, 3H, H-6); 13C NMR (100 MHz, CDCl3) δ: 169.94,
169.86, 138.14, 132.38, 129.89, 129.29, 85.94, 71.19, 71.08, 69.29, 67.59, 21.05,
20.85, 20.76, 20.63, 17.25.
p-Tolyl 2,3,4-tri-O-acetyl-1-thio-β-L-fucopyranoside (2e)
1H NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 7.8 Hz, 2H, ArH), 7.12 (d, J =
7.8 Hz, 2H, ArH), 5.25 (d, J = 3.5 Hz, 1H, H-4), 5.19 (t, J = 9.9 Hz, 1H, H-2),
5.03 (dd, J = 3.5, 9.8 Hz, 1H, H-3), 4.63 (d, J = 9.8 Hz, 1H, H-1), 3.80 (q, J =
6.4 Hz, 1H, H-5), 2.33 (s, 3H, STol-CH3), 2.14 (s, 3H, Ac), 2.10 (s, 3H, Ac),
1.98 (s, 3H, Ac), 1.24 (d, J = 6.7 Hz, 3H, H-6); 13C NMR (100 MHz, CDCl3)
δ: 170.59, 170.11, 169.46, 138.15, 132.84, 129.67, 129.56, 129.00, 86.80, 73.04,
72.39, 70.27, 67.32, 21.09, 20.84, 20.62, 20.59, 16.40.
p-Tolyl 2,3,4-tri-O-acetyl-1-thio-β-D-xylopyranoside (2f)
1H NMR (400 MHz, CDCl3) δ: 7.36 (d, J = 7.8 Hz, 2H, ArH), 7.12 (d, J =
7.8 Hz, 2H, ArH), 5.16 (t, J = 8.5 Hz, 1H, H-2), 4.92–4.88 (m, 2H, H-3, H-4),
4.70 (d, J = 8.6 Hz, 1H, H-1), 4.24 (dd, J = 4.7, 11.7 Hz, 1H, H-5a), 3.38 (dd, J =
9.0, 11.7 Hz, 1H, H-5b), 2.33 (s, 3H, STol-CH3), 2.07 (s, 3H, Ac), 2.03 (s, 3H,
Ac), 2.02 (s, 3H, Ac); 13C NMR (100 MHz, CDCl3) δ: 169.9, 169.7, 169.3, 138.5,
133.4, 129.7, 128.0, 86.3, 72.2, 69.7, 68.4, 65.3, 21.1, 20.7, 20.6; HRMS calcd
for C18H22O7SNa (M+Na)+: 405.0984, found: 405.0973.
p-Tolyl 2,3,4-tri-O-acetyl-1-thio-β-L-arabinopyranoside (2g)
1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J = 8.2 Hz, 2H, ArH), 7.11 (d, J =
7.8 Hz, 2H, ArH), 5.29–5.21 (m, 2H, H-2, H-4), 5.08 (dd, J = 3.1, 8.6 Hz, 1H,

Synthesis of Per-O-acetylated Thioglycosides
579
H-3), 4.73 (d, J = 8.2 Hz, 1H, H-1), 4.13 (dd, J = 3.9, 12.9 Hz, 1H, H-5a),
3.63 (dd, J = 1.9, 12.9 Hz, 1H, H-5b), 2.31 (s, 3H, STol-CH3), 2.08 (s, 3H,
Ac), 2.07 (s, 3H, Ac), 2.03 (s, 3H, Ac); 13C NMR (100 MHz, CDCl3) δ: 170.18,
169.91, 169.37, 138.21, 132.80, 132.70, 129.76, 129.67, 129.33, 87.17, 70.51,
68.36, 67.53, 65.31, 21.08, 20.83, 20.81, 20.70, 20.65.
p-Tolyl 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-
β-D-glucopyranoside (2h)
1H NMR (400 MHz, CDCl3) δ: 7.88 (dd, J = 3.2, 5.5 Hz, 2H, ArH), 7.77 (dd,
J = 2.8, 5.2 Hz, 2H, ArH), 7.31 (d, J = 7.9 Hz, 2H, ArH), 7.08 (d, J = 7.9 Hz,
2H, ArH), 5.78 (t, J = 9.1, 10.3 Hz, 1H, H-3), 5.66 (d, J = 10.7 Hz, 1H, H-1),
5.13 (t, J = 9.5, 9.9 Hz, 1H, H-4), 4.32 (t, J = 10.3, 10.7 Hz, 1H, H-2), 4.31–4.19
(m, 2 H, H-6), 3.93–3.84 (m, 1 H, H-5), 2.33 (s, 3 H, STol-CH3), 2.11 (s, 3 H, Ac),
2.03 (s, 3 H, Ac), 1.84 (s, 3 H, Ac); 13C NMR (100MHz, CDCl3) δ: 170.64, 170.10,
169.44, 167.82, 166.93, 138.75, 134.43, 133.91, 129.62, 126.90, 123.67, 83.08,
75.80, 71.62, 68.65, 62.16, 53.55, 21.15, 20.75, 20.60, 20.39.
p-Tolyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-
β-D-glucopyranoside (2i)
1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J = 7.8 Hz, 2H, ArH), 7.11 (d, J =
7.4 Hz, 2H, ArH), 5.66 (d, J = 8.6 Hz, 1H, NH), 5.20 (t, J = 9.8 Hz, 1H, H-3),
5.03 (t, J = 9.4, 9.8 Hz, 1H, H-4), 4.79 (d, J = 10.2 Hz, 1H, H-1), 4.23–4.14 (m,
2H, H-6, H-6), 3.98 (q, J = 9.8 Hz, 1H, H-2), 3.70 (m, 1H, H-5), 2.34 (s, 3H,
STol-CH3), 2.08 (s, 3H, Ac), 2.01 (s, 3H, Ac), 2.00 (s, 3H, Ac), 1.99 (s, 3H, Ac);
13C NMR (100 MHz, CDCl3) δ: 171.00, 170.63, 170.00, 169.32, 138.40, 133.22,
129.63, 128.31, 86.71, 75.67, 73.73, 68.36, 62.32, 53.22, 23.29, 21.12, 20.71,
20.65, 20.55.
p-Tolyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-
β-D-galactopyranoside (2j)
1H NMR (400 MHz, CDCl3) δ: 7.40 (d, J = 8.2 Hz, 2H, ArH), 7.10 (d, J =
8.2 Hz, 2H, ArH), 5.62 (d, J = 9.4 Hz, 1H, NH), 5.36 (d, J = 3.1 Hz, 1H, H-4),
5.18 (dd, J = 3.1, 10.8 Hz, 1H, H-3), 4.84 (d, J = 10.2 Hz, 1H, H-1), 4.21–4.08
(m, 3H, H-2, H-6a, H-6b), 3.90 (t, J = 6.4 Hz, 1H, H-5), 2.32 (s, 3H, STol-CH3),
2.12 (s, 3H, Ac), 2.02 (s, 3H, Ac), 1.98 (s, 3H, Ac), 1.97 (s, 3H, Ac); 13C NMR
(100 MHz, CDCl3) δ: 170.57, 170.41, 170.26, 170.24, 138.09, 132.63, 129.59,
129.16, 87.48, 74.30, 71.09, 66.88, 61.78, 49.69, 23.40, 21.09, 20.66.

S. Yan et al.
580
Methyl (p-tolyl 5-acetamido-4,7,8,9-tetra-O-acetyl-
3,5-dideoxy-2-thio-D- glycero-β-D-galacto-non-
2-ulopyranoside)-onate (2k)
1H NMR (400 MHz, CDCl3) δ: 7.33 (d, J = 12.8 Hz, 2H, ArH), 7.12 (d, J =
7.9 Hz, 2H, ArH), 5.92 (br d, 1H, NH), 5.48 (s, 1H), 5.39 (td, J = 1.1, 4.2 Hz, 1H,
H-4), 4.96 (d, J = 13.9 Hz, 1H), 4.64 (dd, J = 2.3, 10.5 Hz, 1H), 4.50 (dd, J =
1.9, 12.2 Hz, 1H), 4.13 (dd, J = 4.3, 13.4 Hz, 1H), 4.03 (dd, J = 8.7, 7.2 Hz, 1H),
3.59 (s, 3H, CH3O), 2.64 (dd, J = 9.1, 4.7 Hz, 1H), 2.32 (s, 3H, STol-CH3), 2.14
(s, 3H, Ac), 2.12 (s, 3H, Ac), 2.14–2.02 (m, 1H), 2.08 (s, 3H, Ac), 1.95 (s, 3H, Ac),
1.89 (s, 3H, Ac); 13C NMR (100 MHz, CDCl3) δ: 171.23, 170.95, 170.35, 170.26,
168.27, 140.14, 136.19, 129.84, 125.09, 88.73, 73.13, 72.96, 69.03, 68.74, 62.63,
52.58, 49.32, 37.27, 23.14, 21.30, 21.09, 20.87, 20.72, 20.69.
p-Tolyl O-(2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-
(1→4)-2,3,6-tri-O- acetyl-1-thio-β-D-glucopyranoside (2l)
1H NMR (400 MHz, CDCl3) δ: 7.35 (d, J = 7.8 Hz, 2H, ArH), 7.09 (d,
J = 7.8 Hz, 2H, ArH), 5.32 (dd, J = 0.8, 2.3 Hz, 1H), 5.18 (t, J = 9.0 Hz,
1H), 5.08 (dd, J = 7.8 Hz, 1H), 4.92 (dd, J = 3.5, 10.6 Hz, 1H), 4.84 (t, J =
9.4, 9.8 Hz, 1H), 4.58 (d, J = 10.1 Hz, 1H), 4.51 (dd, J = 1.8, 12.1 Hz, 1H),
4.44 (d, J = 7.8 Hz, 1H), 4.11–4.02 (m, 3H), 3.84 (t, J = 6.6 Hz, 1H), 3.71 (t,
J = 9.4, 9.8 Hz, 1H), 3.61 (m, 1H), 2.32 (s, 3H, STol-CH3), 2.13 (s, 3H, Ac),
2.10 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.03 (s, 3H, Ac), 2.02 (s, 3H, Ac), 2.01 (s, 3H,
Ac), 1.95 (s, 3H, Ac); 13C NMR (100 MHz, CDCl3) δ: 170.27, 170.22, 170.09,
170.01, 169.68, 169.51, 168.98, 138.59, 133.67, 129.56, 127.60, 100.92, 85.55,
76.54, 76.01, 73.80, 70.88, 70.57, 70.13, 68.97, 66.50, 62.00, 60.69, 21.11, 20.78,
20.73, 20.72, 20.57, 20.54, 20.44.
p-Tolyl O-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl)-
(1→4)-2,3,6- tri-O-acetyl-1-thio-β-D-glucopyranoside (2m)
1H
NMR
(400
MHz,
CDCl3)
δ:
7.35
(d,
J = 8.2 Hz, 2H, ArH), 7.11 (d, J = 8.2 Hz, 2H, ArH), 5.39–5.24 (m, 3H),
5.03 (t, J = 9.8, 10.1 Hz, 1H), 4.83 (dd, J = 4.0, 10.4 Hz, 1H), 4.75 (t, J = 9.4,
9.8 Hz, 1H), 4.64 (d, J = 9.8 Hz, 1H, H-1), 4.53 (dd, J = 2.7, 12.1 Hz, 1H),
4.25–4.17 (m, 2H), 4.03 (dd, J = 2.4, 12.5 Hz, 1H), 3.94–3.89 (m, 2H), 3.69 (m,
1H), 2.34 (s, 3H, STol-CH3), 2.12 (s, 3H, Ac), 2.09 (s, 3H, Ac), 2.07 (s, 3H, Ac),
2.03 (s, 3H, Ac), 2.02 (s, 3H, Ac), 1.99 (s, 3H, Ac), 1.97 (s, 3H, Ac); 13C NMR
(100 MHz, CDCl3) δ: 170.49, 170.30, 170.13, 169.87, 169.49, 169.38, 138.78,
134.01, 129.59, 127.04, 95.44, 85.05, 76.45, 75.98, 72.25, 70.55, 69.89, 69.22,
68.40, 67.91, 62.70, 61.40, 21.13, 20.85, 20.76, 20.68, 20.62, 20.54, 20.52, 20.50.

Synthesis of Per-O-acetylated Thioglycosides
581
ACKNOWLEDGEMENTS
This work was supported by the National Natural Science Foundation of China
(81072525 and 21002014) and the Scientific Research Foundation for the Re-
turned Overseas Chinese Scholars. The authors thank Prof. Jianjun Zhang for
providing 2-phthalimdo-2-deoxy-D-glucopyranose (prepared in the Key Tech-
nologies R&D Program of China, 2012BAK25B03, CAU) as a starting material.
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