Evaluating the reactivity and stereoselectivity of salicyl-type thioglycosides as non-malodorous thioglycoside alternatives for oligosaccharide synthesis

Article abstract of DOI:10.1080/07328303.2021.1921787

Herein, o-(methoxycarbonyl)phenyl thioglycosides [or (methyl)salicyl 1-thioglycosides] were evaluated as non-malodorous thioglycoside alternatives. The o-methoxycarbonyl group was expected to assist in the departure of leaving group. Salicyl-type thioglyc

Full text of DOI:10.1080/07328303.2021.1921787

Journal of Carbohydrate Chemistry
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Evaluating the reactivity and stereoselectivity of
salicyl-type thioglycosides as non-malodorous
thioglycoside alternatives for oligosaccharide
synthesis
Hirofumi Dohi, Risa Sakurai, Manami Tamura, Ryota Komai & Yoshihiro
Nishida
To cite this article: Hirofumi Dohi, Risa Sakurai, Manami Tamura, Ryota Komai & Yoshihiro
Nishida (2021): Evaluating the reactivity and stereoselectivity of salicyl-type thioglycosides as
non-malodorous thioglycoside alternatives for oligosaccharide synthesis, Journal of Carbohydrate
Chemistry, DOI: 10.1080/07328303.2021.1921787
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JOURNAL OF CARBOHYDRATE CHEMISTRY
https://doi.org/10.1080/07328303.2021.1921787
Evaluating the reactivity and stereoselectivity of salicyl-
type thioglycosides as non-malodorous thioglycoside
alternatives for oligosaccharide synthesis
Hirofumi Dohia,b , Risa Sakuraia, Manami Tamuraa, Ryota Komaia, and
Yoshihiro Nishidaa,b
aApplied Biological Chemistry Field of Biomolecular Chemistry, Graduate School of Horticulture,
b
Chiba University, Chiba, Japan; Molecular Chirality Research Center, Chiba University,
Chiba, Japan
ABSTRACT
ARTICLE HISTORY
Received 26 February 2021
Accepted 21 April 2021
Herein, o-(methoxycarbonyl)phenyl thioglycosides [or (methyl)-
salicyl 1-thioglycosides] were evaluated as non-malodorous
thioglycoside alternatives. The o-methoxycarbonyl group was
expected to assist in the departure of leaving group. Salicyl-
type thioglycosides exhibited high reactivity and glycosylation
yields when N-iodosuccinimide and trifluoromethanesulfonic
acid were used as promoters. Glycosylation with these thiogly-
cosides in dichloromethane showed similar reactivity and
stereoselectivity as those of phenyl thioglycosides.
Glycosylation with per-O-benzyl salicyl-type thioglycosides in
dichloromethane showed 1,2-cis-selectivity, while the same
reaction in nitriles afforded predominantly 1,2-trans glycosides.
In contrast, glycosylation with per-O-benzoyl thioglycosides
afforded exclusively 1,2-trans glycosides. These results strongly
suggest that salicyl-type thioglycosides can serve as non-mal-
odorous alternatives for phenyl thioglycosides.
KEYWORDS
Glycosylation; thioglycoside;
carbohydrate;
oligosaccharide
GRAPHICAL ABSTRACT
Introduction
Since the importance of glycoconjugates has been recognized in diverse
biological processes,[1] the development of practical methods for their
CONTACT Hirofumi Dohi
hdohi@faculty.chiba-u.jp; Yoshihiro Nishida
ynishida@faculty.chiba-u.jp
Applied Biological Chemistry Field of Biomolecular Chemistry, Graduate School of Horticulture, Chiba University,
Chiba 263-8522, Japan; Molecular Chirality Research Center, Chiba University, Chiba, Japan.
ß 2021 Taylor & Francis Group, LLC

2
H. DOHI ET AL.
synthesis is strongly desired to evaluate their biological functions based on
precise and exact molecular information. Among the chemical methodolo-
gies for carbohydrate synthesis, glycosylation procedures have attracted
considerable attention because the anomeric configuration along with the
location of the glycosidic bond are crucial for the structure-activity rela-
tionships of glycoconjugates. The current glycosylation methodologies
involve the activation of a sugar unit with a leaving group at the anomeric
position (glycosyl donor) in the presence of an appropriately protected
sugar unit with a free hydroxyl group (glycosyl acceptor). The stereoselect-
ivity of glycosylation is controlled by several factors, such as the type of
solvent and the reaction temperature. The structure of glycosyl donor and
the chemical properties of leaving and protecting groups, in particular, are
also crucial factors for determining the configuration. Therefore, carbohy-
drate chemists have devoted significant efforts to the development of vari-
ous glycosyl donors for controlling the stereoselective formation of
glycosidic bonds. Thioglycosides such as aryl and alkyl thioglycosides, along
with glycosyl halides and imidates, have been extensively employed as gly-
cosyl donors for the construction of both 1,2-trans and 1,2-cis glycosides[2]
owing to their high chemical stability during regioselective protection of
the parent sugar unit. Furthermore, thioglycosides can be readily synthe-
sized by treatment of a thiol with a per-O-acetylated sugar in the presence
of an appropriate acid or with a glycosyl bromide under basic conditions.
One of the most remarkable features of thioglycosides is that their thiogly-
cosidic bonds can be orthogonally activated by multiple thiophiles, such as
halogen and alkyl cations, in the presence of glycosyl acceptors bearing a
heterogeneous aglycon. This feature allows for sequential glycosyla-
tion reactions.
However, from a practical viewpoint, the unpleasant smell arising from
the mercaptans during the preparation of the thioglycosides is a major
impediment in the use of these glycosyl donors for oligosaccharide synthe-
sis. To overcome this problem, several studies have been conducted on the
odorless formation of thioglycosyl donors[3] such as using tolyl,[4–8]
lauryl,[9,10] (2-methyl-5-tert-butyl)phenyl[11–13] and alkylphenyl[14,15] thio-
glycosides. In our efforts to develop a novel class of non-malodorous thio-
glycosides, we focused on methyl thiosalicylate. Most alkyl and aryl thiols
possess an unpleasant odor, even those with high boiling points. In con-
trast, methyl thiosalicylate has an inoffensive odor, which somewhat resem-
bles the odor of methyl salicylate.
Using methyl thiosalicylate, we have previously reported non-malodorous
thioglycosides 1 (Fig. 1), which can be prepared without the emission of an
unpleasant odor and has been shown to serve as a glycosyl donor in a
manner similar to conventional thioglycosides.[16] These thioglycosides

JOURNAL OF CARBOHYDRATE CHEMISTRY
3
Figure 1. Non-malodorous salicyl-type phenylthioglycosides 1.
Figure 2. Designed (methoxycarbonyl)phenyl thioglycosides 2–7.
allowed us to synthesize bioactive oligosaccharides, e.g., globo-series[17] and
LewisX[18] oligosaccharides, and glycoglycerolipids.[19] To confirm the wide
applicability of our non-malodorous thioglycosides for oligosaccharide syn-
thesis, extensive investigation of their behavior in glycosylation reactions
under various conditions is important.
In this study, we prepared a series of salicyl-type thioglycosides with
either benzyl or benzoyl protecting groups and subjected them to glycosyla-
tion with glycosyl acceptors having primary or secondary alcohols under
various conditions. Their reactivity and stereoselectivity were compared
with those of the corresponding phenyl thioglycosides and regioisomeric
m- and p-(methoxycarbonyl)phenyl thioglycosides.
Results and discussion
Previously, we demonstrated that per-O-benzyl salicyl-type thioglycosides
can serve as glycosyl donors to promote 1,2-trans glycosylation of a pri-
mary alcohol at a low temperature; however, the use of sterically hindered
secondary alcohols afforded 1,2-cis glycosylation.[16–19] The details of these
reactions, particularly the promoter sensitivity, temperature dependence of
stereoselectivity and reactivity, remain unclear. Therefore, o-(methoxycar-
bonyl)phenyl thioglycosides 2[16,17] and 3[19] (Fig. 2), as well as m- and
p-(methoxycarbonyl)phenyl thioglycosides 4 and 5, were prepared to
investigate the effect of the methoxycarbonyl group on the reactivity and
stereoselectivity in glycosylation. Moreover, the 2-O-acyl group-assisted
1,2-trans glycosylation of our non-malodorous phenyl thioglycosides has
not yet been investigated. Hence, per-O-benzoyl salicyl-type thioglycosides
6 and 7 were prepared to demonstrate the wide applicability of

4
H. DOHI ET AL.
Scheme 1. Reagents and conditions: (a) methyl thiosalicylate, BF3ꢀOEt2, CH2Cl2, r.t, 2 h, 79%; (b)
(i) NaOMe, MeOH, r.t., 3 h (ii) BnBr, NaH, DMF, 0 ꢁC!r.t., 24 h, 79% (2 steps); (c) 3- or 4-mercap-
tobenzoate, K2CO3, DMF, r.t., 2–4 h, 72–82%; (d) (i) NaOMe, MeOH, r.t., 4 h (ii) BnBr, NaH, DMF,
0 ꢁC!r.t., 14–19 h, 63–65% (2 steps); (e) (i) NaOMe, MeOH, r.t., 2 h (ii) BzCl, Py, 0 ꢁC!r.t., 12 h,
92–96% (2 steps).
o-(methoxycarbonyl)phenyl thioglycosides for oligosaccharide synthesis
including 1,2-trans glycosylation.
Per-O-benzylated galactosyl thioglycoside 2 was prepared from per-O-
acetyl-b-galactopyranose (Scheme 1). The prr-O-acetate was treated with
methyl thiosalicylate in the presence of BF3ꢀOEt2 to afford the correspond-
ing thiogalactoside 8, and the acetyl groups in each thioglycoside were then
converted to benzyl groups via deacylation and benzylation to afford 2.
During benzylation, an undesired, transesterified byproduct was generated,
possibly because of the poor stability of the methyl ester group under
strongly basic conditions (NaH/BnBr), resulting in a poor yield of 2. This
could be avoided by the prolonged stirring of reaction mixture after
quenching of the reaction upon addition of excess methanol, which pro-
motes transesterification to produce the desired methyl ester 2. BF3ꢀOEt2
catalyzed thioglycosydation using methyl 3- and 4-mercaptobenzoates was
unsuccessful because of dimerization of the mercaptobenzoates; therefore,
m- and p-(methoxycarbonyl)phenyl isomers 4 and 5 were prepared via gal-
actosyl bromide. Galactosyl bromide was reacted with methyl mercaptoben-
zoate in the presence of K2CO3 to afford the corresponding m- and
p-(methoxycarbonyl)phenyl thiogalactosides 9 and 10, respectively, which
were subsequently converted to furnish m- and p-(methoxycarbonyl)
phenyl thiogalactosides 4 and 5 on deacylation and then benzylation.

JOURNAL OF CARBOHYDRATE CHEMISTRY
5
Table 1. Promoter sensitivity of salicyl thiogalactoside 2.
Entry
Promoter (eq)
Temp. ꢁC
Time
Yield %
a/bb
1
2
3
4
5
6
7
NIS (1.2) / TfOH (0.1)
NIS (1.2) / TfOH (0.5)
NBS (1.5)
AgOTf (1.0)
Cu(OTf)2 (1.0)
TMSOTf (1.0)
MeOTf (3.0)
ꢂ78
ꢂ78
0
0
0
0
r.t,
48 h
30 min
24 h
48 h
48 h
48 h
5 h
83
>99
19
1/3.9
1/6.7
4/1
c
n.r.a
5
-
2.8/1
n.r.a
88
-
c
1.9/1
aNot reacted.
1
c
bDetermined by H NMR. Not determined.
Per-O-benzoylated thioglycosides 6 and 7 were obtained from per-O-ace-
tates 8 and 11,[19] respectively, via successive deacetylation and benzoyla-
tion reactions.
With the designed non-malodorous thioglycosides in hand, the glycosyla-
tion of alcohols with (o-methoxycarbonyl)phenyl thioglycosides 2 and 4–7
was investigated and their reactivity and stereoselectivity were compared to
the glycosylation reactions using corresponding phenyl thioglycosides.
Initially, per-O-benzylated o-(methoxycarbonyl)phenyl thioglycoside 2 was
subjected to glycosylation of glucoside 12 with a primary alcohol[20] in
dichloromethane using a series of Lewis acids, which have been reported to
serve as promoters for several glycosyl donors (Table 1). A combination of
N-iodosuccinimide (NIS, 1.2 eq.) and trifluoromethanesulfonic acid (TfOH,
0.1 eq.), a typical promoter for phenyl thioglycosides, activated 2 at ꢂ78 ꢁC
to afford the desired disaccharide (entry 1). The disaccharide could be eas-
ily separated from methyl thiosalicylate residue by silica gel column chro-
matography. However, some amount of donor 2 remained unreacted even
after 48 h, resulting in an insufficient yield of glycosylation product. Using
a greater amount of TfOH (0.5 eq.) solved this problem, leading to the for-
mation of the disaccharide in a good yield, even at a low temperature
(entry 2). Note that large amount of TfOH obviously increased the
b-selectivity. This phenomenon might be attributed to increase of an a-tri-
flate, which assists SN2-like substitution by the reactive primary alcohol. N-
Bromosuccinimide (NBS) promoted glycosylation resulted in poor yield
because of the presence of inseparable side products such as N-succinimidyl
glycoside (entry 3). Metal triflates such as AgOTf and Cu(OTf)2, which
have been reported as excellent promoters for S-benzoxazolyl (SBox) glyco-
sides,[21] were inactive for 2 (entries 4 and 5). Similarly, trimethylsilyl

6
H. DOHI ET AL.
Table 2. Glycosylation using salicyl and phenyl thiogalactosides 2 and 14.
Entry
1
Donor
Acceptor
Temp. ꢁC
0
Time
Yield %
a/ba
15 min
>99
1/1.4
2
2
0
5 min
>99
1/1.3
14
2
14
2
14
2
14
12
13
3
4
5
6
7
8
ꢂ78
ꢂ78
0
30 min
30 min
15 min
5 min
1.5 h
30 min
>99
72
61
69
73
1/6.7
1/12
2.1/1
3.3/1
1/1.1
1.1/1
0
ꢂ78
ꢂ78
85
9b
2
0
1 h
89
4.9/1
15
1
aDetermined by H NMR.
b[16].
trifluoromethanesulfonate (TMSOTf), a typical promoter of glycosyl imi-
dates, was unable to activate o-(methoxycarbonyl)phenyl thioglycosides
either (entry 6). For the phenyl thioglycosides, methyl triflate acted as a
promoter to afford the disaccharide in excellent yield (entry 7). These
results indicated that the non-malodorous thioglycoside 2, despite having a
methoxycarbonyl group at the ortho position of the thioether, was able to
undergo an activation mechanism similar to that of conventional phenyl
thioglycosides, i.e., via activation of the thioether by halogen cations.
Considering the promoter sensitivity of our non-malodorous thioglyco-
sides, glucosides with primary and secondary hydroxyl groups 12 and
13[20] were subsequently coupled with thioglycosides 2, as well as phenyl
[22]
thioglycosides 14,
using the NIS/TfOH system. The yields and a/b
ratios of the resulting disaccharides are listed in Table 2. The glycosylation
reaction was conducted using 1.2 eq. of glycosyl donor (with respect to gly-
cosyl acceptor) along with a combination of NIS and TfOH (1.2 and 0.5
eq., respectively). Glycosylation with per-O-benzylated galactosyl donor 2

JOURNAL OF CARBOHYDRATE CHEMISTRY
7
slightly favored the formation of b-anomer at 0 ꢁC (a/b ¼ 1/1.4, entry 1).
This tendency became more evident at lower temperatures, and higher
b-selectivity (a/b ¼ 1/6.7) was observed at ꢂ78 ꢁC (entries 1 and 2).
Glycosylation with 14 at ꢂ78 ꢁC showed slightly higher b-selectivity than
that with 2 (a/b ¼ 1/12, entry 4). Although 4-O-benzyl group of galactosyl
donors 2 and 14 blocks the b-face to promote a-glycosylation, glycosyla-
tions at low temperatures showed excellent b-selectivity. These result were
presumably originated from the predominance of SN2-like substitution with
glycosyl a-triflate, whose chemical stability is much higher at low tempera-
tures. In contrast to glycosylation of primary alcohol 12, glycosylation of
secondary alcohol 13 with 2 showed a-selectivity. These glycosylation reac-
tions were expected to show a-selectivity because the steric effect of 4-O-
benzyl group affects strongly against secondary alcohols. However, when
the reaction was conducted at a lower temperature, the reaction showed
b-selectivity (entries 5 and 7). As in the case of glycosylation with a pri-
mary alcohol, the observed b-selectivity can also be rationalized by the
enhancement of the stability of the a-glycosyl triflate to promote SN2-like
nucleophilic substitution. These results are contrary to our previous obser-
vation that the glycosylation of a sterically hindered secondary alcohol
favors the formation of a-glycoside. For example, glycosylation of galactosyl
acceptor 15 with galactosyl donor 2 at 0 ꢁC showed a-selectivity (a/b ¼ 4.9/
1, entry 9).[16] This contradiction can be attributed to the different reactiv-
ities of the acceptor alcohols. In galactosyl acceptor 15 with a 4-OH, which
showed high a-selectivity, the hydroxyl group was in the axial position, and
an electron-withdrawing acetyl group was at the neighboring 3-O position.
These factors remarkably decreased the reactivity of the alcohol. Compared
to glycosyl acceptor 13, which had an equatorial hydroxyl group with an
electron-donating benzyl group at the neighboring 3-O position, 15 was
endowed with sufficient reactivity to induce SN2-like substitution with the
unstable b-triflate during in situ anomerization, although the reactivity was
insufficient to react with the more stable a-triflate. In contrast, phenyl thio-
galactoside 14 showed slightly higher reactivity than salicyl-type thioglyco-
side 2 in glycosylation with secondary alcohol 13 (entries 7 and 8). This
difference in reactivity could be explained by the fact that the electron-
withdrawing o-methoxycarbonyl group of 2 decreased the electron density
on the sulfur atom.
Next, glycosylation reactions of gluco-type thioglycoside 3 were examined
at ꢂ78 ꢁC and the results are presented in Table 3. Overall, glycosylation
with glucose donor 3 led to similar results as in the case of donor 2 except
for the observation of higher b-selectivity at ꢂ78 ꢁC (entry 1). This phe-
nomenon is likely attributed to the higher chemical stability of glucosyl tri-
flate than that of the galactosyl triflate. The reactivities of gluco-type

8
H. DOHI ET AL.

JOURNAL OF CARBOHYDRATE CHEMISTRY
9
donors were obviously lower than those of galacto-type donors, probably
due to the difference in the activation energy over the oxocarbenium inter-
mediate. Unlike o-(methoxycarbonyl)phenyl thioglucoside 3, phenyl thio-
glucoside 16[22] was found to glycosylate 12 quickly even at ꢂ78 ꢁC (entries
1 and 2). As in the case of primary alcohol, phenyl thioglucoside 16 also
demonstrated higher reactivity than the salicyl-type thioglycoside 3 in gly-
cosylation with the secondary alcohol 13 (entry 3 and 4). As shown in
Tables 2 and 3, salicyl-type thioglycosides may show similar stereoselectiv-
ity and yields as phenyl thioglycosides, whereas salicyl-type thioglycosides
displayed slightly lower reactivities than phenyl thioglycosides at low tem-
perature. This result indicated the role of the o-methoxycarbonyl group in
determining the reactivity in glycosylation.
To gain insights into the role of the o-methoxycarbonyl group in glycosyla-
tion, we investigated glycosylation using m- and p-(methoxycarbonyl)phenyl
thioglycosides 4 and 5 at ꢂ78 ꢁC and compared their reactivity and stereo-
selectivity with those of the o-isomer 2 (Table 4). Regardless of the type of gly-
cosyl acceptor, m-isomer 4 showed the highest reactivity, which is comparable
to those of phenyl thioglycoside (entries 2 and 5). This result can be rational-
ized by the fact that the electron-withdrawing methoxycarbonyl group in 4 is
located at the meta position of the thioether group. In contrast, the reactivities
of o- and p-isomers 2 and 5 were apparently different, possibly because the thi-
oether group in these instances experienced a different magnitude of the elec-
tron withdrawal effect due to the methoxycarbonyl group. This phenomenon
was probably due to the fact that the o-carbonylgroup in 2 formed an
orthoester-like intermediate by the attack of carbonyl oxygen at the anomeric
center, which assisted in the departure of the thioether group from the anome-
ric center of 2, as is the case with a superarmed donor.[23]
We subsequently turned our attention to the applicability of the stereo-
chemical regulation by solvent effects and 2-O-acyl participation in glycosy-
lation using our non-malodorous phenyl thioglycosides (Table 5). The
glycosylation of primary alcohol 12 with (o-methoxycarbonyl)phenyl thio-
galactoside 2 was initially conducted in solvents such as nitriles and ethers
that promote stereoselectivity. Compared to dichloromethane, acetonitrile
enhanced b-selectivity when glycosylation was conducted at ꢂ35 ꢁC
(a/b ¼ 1/9, entry 1), and the glycosylation in propionitrile at ꢂ60 ꢁC further
increased this tendency (a/b ¼ 1/16, entry 2). The combination of cyclopen-
tyl methyl ether and chloroform (3/1), which has been reported to induce
1,2-cis-selective glycosylation,[24] possibly promoted a-selective glycosyla-
tion (entry 3). For glycosylation of the secondary alcohol 13, the use of
nitriles as solvents drastically shifted the stereoselectivity toward the
b-glycoside product (entry 4). Each glycosylation using glucosyl donor in
acetonitrile or cyclopentyl methyl ether and chloroform (3/1) showed

10
H. DOHI ET AL.

JOURNAL OF CARBOHYDRATE CHEMISTRY
11
Table 5. Solvent effects and 2-O-acyl participation in glycosylation using nonmalodorous phe-
nyl thioglycosides.
Time
h
Yield
%
Entry
Donor
Acceptor
Solvent
MeCN
EtCN
MeCN
CPME/CHCl3
(3/1)
Temp. ꢁC
a/ba
1
2
3
4
2
2
2
2
12
12
13
12
ꢂ35
ꢂ60
ꢂ35
r.t.
6
96
78
80
89
1/9
4.5
1.5
24
1/16
1/2.7
1.6/1
5
6
3
3
13
12
MeCN
CPME/CHCl3
(3/1)
ꢂ35
4
24
94
82
1/4.5
3.7/1
r.t.
7
8
9
10
6
7
6
7
1
12
12
13
13
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
0
0
0
0
2.5
1.5
2.5
1.5
93
88
98
97
>1/19
>1/19
>1/19
>1/19
aDetermined by H NMR.
solvent effect to give b- or a-selectivity, respectively (entries 5 and 6).
Then, neighboring group participation-assisted stereoselective glycosylation
was confirmed using per-O-benzoylated non-malodorous phenyl thioglyco-
sides. The per-O-benzoylated glycosyl donor 6 could be activated smoothly
under the same conditions as for the per-O-benzylated analogues to glyco-
sylate the primary alcohol 12, giving exclusively the b-glycosylated disac-
charide. A similar result was obtained using the glycose-type donor 7
(a/b > 1/19, entries 7 and 8). Moreover, the glycosylation of secondary
alcohol 13 with the per-O-benzoylated thioglycosides 6 and 7 proceeded
stereoselectively to afford exclusively b-glycosides (a/b > 1/19, entries 9 and
10). These results support the theory that salicyl-type thioglycosides
undergo solvent effects and 2-O-acyl participation similar to conventional
glycosyl donors. Although the reactivity was slightly lower, salicyl thiogly-
cosides exhibited reaction behaviors similar to phenyl thioglycosides, indi-
cating that our non-malodorous thioglycosides can be used for
oligosaccharide synthesis. These results indicated that salicyl-type thioglyco-
sides have great potential as non-malodorous phenyl thioglycoside alterna-
tives for oligosaccharide synthesis.

12
H. DOHI ET AL.
Conclusion
In summary, a series of o-(methoxycarbonyl)phenyl thioglycosides were
synthesized via an alternative pathway to access the previously reported o-
(methoxycarbonyl)phenyl thiogalactoside using per-O-acetylated b-D-galact-
ose and methyl thiosalicylate in the presence of BF3ꢀOEt2. A comprehensive
investigation of their reactivity and stereoselectivity in glycosylation reac-
tions has shown that all the salicyl-type thioglycosides can function as gly-
cosyl donors when a combination of NIS and TfOH was used as the
promoter. Although their reactivities were slightly lower than those of con-
ventional phenyl thioglycosides, the resulting reaction yields and stereo-
chemical outcomes were comparable to those of authentic thioglycosides.
The o-methoxycarbonyl group of salicyl-type thioglycosides was expected
to not only decrease the reactivity by the electron withdrawal effect but
also assist in the departure of the thioether group by the formation of an
orthoester-like intermediate. The stereoselectivities of the designed salicyl-
type thioglycosides could be controlled by solvent effects and neighboring
group participation of the 2-O-acyl group as well as the reaction tempera-
ture, promoting 1,2-trans- or 1,2-cis-selective glycosylation. Hence, the
promising efficacy of our non-malodorous thioglycosides for oligosacchar-
ide synthesis is expected to solve the problem of unpleasant odors arising
during the preparation of thioglycosides. The investigation of modified sal-
icyl-type thioglycosides and their use in the synthesis of oligosaccharides is
in progress and these results will be reported elsewhere.
Experimental section
General methods
All reactions were carried out under a dry argon atmosphere. Yields refer
to chromatographically and spectroscopically homogeneous material.
Anhydrous solvents were purchased from Wako Pure Chemical Industries
Co., Ltd. All other chemicals for the syntheses were purchased from Wako
Pure Chemical Industries Co., Ltd. (Osaka, Japan), Sigma-Aldrich Co., or
Tokyo Kasei Kogyo (Tokyo, Japan). Reagents were purchased at the highest
commercial quality and used without further purification. All reactions
were monitored by thin-layer chromatography (TLC) carried out on silica
gel 60-F254 precoated plates (Merck) using UV light and cerium sulfate/
molybdic acid solution as visualizing agent. Silica gel BW-80S (average par-
ticle size 100 mesh, Fuji Silicia Chemical Co., Ltd.) or BW-300 (average
particle size 60 mesh, Fuji Silicia Chemical Co., Ltd.) was employed for
flash column chromatography.

JOURNAL OF CARBOHYDRATE CHEMISTRY
13
NMR spectra were recorded with a JEOL ECA 500 spectrometer
1
equipped with Delta 5.02. Unless otherwise stated, H NMR (500 MHz)
spectra were recorded at 25 ꢁC using internal tetramethylsilane (TMS) at
0 ppm, and 13C NMR (125 MHz) spectra were recorded at 125 MHz using
internal CDCl3 at 77.16 ppm. The following abbreviations are used to
explain the multiplicities: s ¼ singlet, d ¼ doublet, t ¼ triplet, m ¼ multiplet,
br ¼ broad. Optical rotations were measured with a JASCO DIP 370 polar-
imeter. HRESIMS spectra were recorded on a ThermoFisher Exactive.
2-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
galactopyranoside (8)
To a solution of penta-O-acetyl-b-D-galactopyranose (12.5 g, 31.9 mmol)
and methyl thiosalicylate (17.6 mL, 128 mmol) in CH2Cl2 (319 mL) was
added BF3ꢀOEt2 (4.0 mL, 31.9 mmol), and the reaction mixture was stirred
at rt for 27 h. The reaction was quenched by addition of Et3N and extracted
with CHCl3. The organic layer was washed with sat. NaHCO3 and brine,
dried over MgSO4, and concentrated under reduced pressure. The residue
was purified by chromatography (silica gel, hexane:EtOAc ¼ 1:1) to give
1
compound 8 (12.5 g, 79%) as a white crystal; [a]D ꢂ22.5 (c 1.0, CHCl3); H
NMR (500 MHz, CDCl3): d 7.90 (dd, 1H, J ¼ 1.4 and 7.6 Hz, ArH), 7.65
(dd, 1H, J ¼ 0.9 and 8.0 Hz, ArH), 7.46 (dt, 1H, J ¼ 1.6 and 7.4 Hz, ArH),
7.30 (dt, 1H, J ¼ 1.1 and 7.6 Hz, ArH), 5.47 (dd, 1H, J3,4 ¼ 3.4 Hz, J4,5
0.9 Hz, H-4), 5.37 (t, 1H, J1,2 ¼ J2,3 ¼ 9.9 Hz, H-2), 5.11 (dd, 1H, J2,3
¼
¼
9.9 Hz, J3,4 ¼ 3.4 Hz, H-3), 4.88 (d, 1H, J1,2 ¼ 10.1 Hz, H-1), 4.20 (dd, 1H,
J5,6a ¼ 7.2 Hz, Jgem ¼ 11.4 Hz, H-6a), 4.13 (dd, 1H, J5,6b ¼ 5.8 Hz, Jgem
¼
11.2 Hz, H-6b), 4.03 (br-dt, 1H, J4,5 ¼ 0.9 Hz, J5,6a ¼ 7 Hz, H-5), 3.90 (s,
3H, CH3OCOAr), 1.99, 2.05, 2.06 and 2.17 (s ꢃ 4, 12H, CH3CO2-); 13C
NMR (125 MHz, CDCl3): d 170.49, 170.34, 170.21, 169.43, 166.92, 136.92,
132.28, 130.88, 130.75, 129.41, 126.36, 84.89, 74.53, 72.16, 67.34, 66.96,
61.91, 52.33, 20.88, 20.81 ꢃ 2, 20.73; HRESIMS: Calcd for C22H26O11S
[M þ NH4]þ 516.1534; found 516.1523.
2-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-
galactopyranoside (2)
To a solution of compound 8 (5.00 g, 10 mmol) in MeOH (80 mL) was
added NaOMe (27 mg, 0.5 mmol), and the reaction mixture was stirred at
rt for 3 h. The reaction was quenched by addition of Amberlite ion-
exchange resin and the mixture was filtered. The filtrate was concentrated
and the residue was coeveporated with toluene. To a solution of the residue
in DMF (100 mL) was added NaH (2.4 g, 60 mmol) and BnBr (7.13 mL,

14
H. DOHI ET AL.
59.2 mmol) slowly at 0 ꢁC, and the reaction mixture was stirred at rt for
24 h. The reaction was quenched by addition of MeOH, and EtOAc was
added to the mixture. The organic layer was washed with brine, dried over
MgSO4, and concentrated under reduced pressure. The residue was purified
by chromatography (silica gel, toluene:EtOAc ¼ 50:1) to give compound 2
(5.43 g, 79% over 2 steps) as a white powder; [a]D ꢂ30.5 (c 1.08, CHCl3);
1H NMR (500 MHz, CDCl3): d 7.86 (dd, 1H, J ¼ 1.8 and 7.5 Hz, ArH), 7.78
(dd, 1H, J ¼ 1.2 and 7.7 Hz, ArH), 7.24–7.37 (m, 20H, ArH), 7.17 (dt, 1H,
J ¼ 1.7 and 7.5 Hz, ArH), 7.14 (dt, 1H, J ¼ 1.4 and 7.7 Hz, ArH), 4.99 (d,
1H, Jgem ¼ 11.5 Hz, ArCH2-), 4.72–4.80 (m, 4H, ArCH2-), 4.77 (d, 1H, J1,2
¼ 8.9 Hz, H-1), 4.61 (d, 1H, Jgem ¼ 11.5 Hz, ArCH2-), 4.49 (d, 1H, Jgem
11.5 Hz, ArCH2-), 4.41 (d, Jgem ¼ 11.7 Hz, 1H, ArCH2-), 4.04 (t, 1H, J1,2
¼
¼
J2,3 ¼ 9.5 Hz, H-2), 4.00 (br-d, 1H, J ¼ 2.6 Hz, H-4), 3.86 (s, 3H,
CH3OCOAr), 3.62–3.68 (m, 4H, H-3, H-5, H-6a and H-6b); 13C NMR
(125 MHz, CDCl3): d 167.02, 139.30, 138.78, 138.34, 138.23, 137.97, 132.45,
130.78, 129.23, 128.90, 128.57, 128.56, 128.38, 128.08, 128.05, 127.95,
127.85, 127.72, 125.10, 86.04, 84.25, 77.48, 77.37, 76.01, 74.60, 73.76, 73.69,
72.90, 69.10, 52.24; HRESIMS: Calcd for C42H46O7NS [M þ NH4]þ
708.2989; found 708.2979.
3-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
galactopyranoside (9)
To a solution of tetra-O-acetyl-a-D-galactopyranosyl bromide (6.66 g,
16.2 mmol) and methyl 3-mercaptobenzoate (3.34 g, 19.4 mmol) in DMF
(84 mL) was added K2CO3 (3.45 g, 24.3 mmol), and the reaction mixture
was stirred at rt for 4 h. The reaction mixture was diluted with EtOAc and
the organic layer was washed with brine three times, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified by
chromatography (silica gel, toluene:EtOAc ¼ 10:1) to give compound 9
(5.84 g, 72%) as a white solid; [a]D ꢂ6.1 (c 2.2, CHCl3); 1H NMR
(500 MHz, CDCl3): d 8.20 (t, 1H, J ¼ 1.7 Hz, ArH), 7.98 (dt, 1H, J ¼ 1.4 and
7.8 Hz, ArH), 7.71 (dq, 1H, J ¼ 1.1, 2.0 and 8.0 Hz, ArH), 7.41 (t, 1H,
J ¼ 7.7 Hz, ArH), 5.43 (dd, 1H, J3,4¼ 3.4 Hz, J4,5¼ 0.86 Hz, H-4), 5.23 (t,
1H, J1,2¼ J2,3¼ 10.0 Hz, H-2), 5.06 (dd, 1H, J2,3¼ 10.0 Hz, J3,4 ¼ 3.4 Hz, H-
3), 4.75 (d, 1H, J1,2¼ 9.7 Hz, H-1), 4.20 (dd, 1H, J5,6a¼ 7.2 Hz, Jgem
¼
11.5 Hz, H-6a), 4.14 (dd, 1H, J5,6b¼ 6.3 Hz, Jgem ¼ 11.5 Hz, H-6b), 3.97 (br-
t, 1H, H-5), 3.93 (s, 3H, CH3OCOAr), 1.98–2.12 (s ꢃ 4, 12H, CH3CO2-);
13C NMR (125 MHz, CDCl3): d170.76, 170.52, 170.38, 169.77, 166.64,
137.10, 133.74, 133.42, 131.29, 129.57, 129.24, 86.53, 74.83, 67.50, 67.46,
61.09, 52.71, 21.18, 21.00, 20.95 ꢃ 2; HRESIMS: Calcd for C22H30O11NS
[M þ NH4]þ 516.1534; found 516.1533.

JOURNAL OF CARBOHYDRATE CHEMISTRY
15
4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
galactopyranoside (10)
To a solution of tetra-O-acetyl-a-D-galactopyranosyl bromide (6.09 g,
14.8 mmol) and methyl 4-mercaptobenzoate (3.00 g, 17.8 mmol) in DMF
(75 mL) was added K2CO3 (3.08 g, 22.3 mmol), and the reaction mixture
was stirred at rt for 2 h. The reaction mixture was diluted with EtOAc and
the organic layer was washed with brine three times, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified by
chromatography (silica gel, toluene:EtOAc ¼ 10:1) to give compound 10
1
(6.06 g, 82%) as a white solid; [a]D 5.7 (c 1.4, CHCl3); H NMR (500 MHz,
CDCl3): d 7.97 (dt, 1H, J ¼ 2.0 and 8.9 Hz, ArH), 7.53 (dt, 1H, J ¼ 1.7 and
7.8 Hz, ArH), 5.46 (dd, 1H, J3,4¼ 3.4 Hz, J4,5¼ 0.9 Hz, H-4), 5.29 (t, 1H,
J1,2¼ J2,3¼ 10.0 Hz, H-2), 5.09 (dd, 1H, J2,3¼ 10.0 Hz, J3,4¼ 3.44 Hz, H-3),
4.84 (d, 1H, J1,2¼ 10.0 Hz, H-1), 4.20 (dd, 1H, J5,6a¼ 7.2 Hz, Jgem
¼
11.5 Hz, H-6a), 4.14 (dd, 1H, J5,6b¼ 5.7 Hz, Jgem ¼ 11.5 Hz, H-6b), 4.01 (br-
t, 1H, H-5), 3.92 (s, 3H, CH3OCOAr), 1.99–2.15 (s ꢃ 4, 12H, CH3CO2-);
13C NMR (125 MHz, CDCl3): d170.73, 170.50, 170.37, 169.76, 166.86,
139.67, 130.67, 130.31, 129.51, 85.87, 75.02, 72.22, 67.53, 67.33, 62.08,
52.61, 21.15, 21.07, 21.03, 20.93; HRESIMS: Calcd for C22H30O11NS
[M þ NH4]þ 516.1534; found 516.1536.
3-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-
galactopyranoside (4)
To a solution of compound 9 (3.56 g, 7.14 mmol) in MeOH (50 mL) was
added NaOMe (19 mg, 0.36 mmol), and the reaction mixture was stirred at
rt for 4 h. The reaction was quenched by addition of Amberlite ion-
exchange resin and the mixture was filtered. The filtrate was concentrated
and the residue was coevaporated with toluene under diminished pressure.
To a solution of the residue in DMF (60 mL) were added NaH (1.71 g,
42.8 mmol) and BnBr (5.12 mL, 42.8 mmol) slowly at 0 ꢁC, and the reaction
mixture was stirred at rt for 14 h. The reaction was quenched by addition
of MeOH, and EtOAc was added to the mixture. The organic layer was
washed with brine, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by chromatography (silica gel,
toluene:EtOAc ¼ 50:1) to give compound 4 (3.21 g, 65% over 2 steps) as a
1
white powder; [a]D ꢂ 5.3 (c 1.19, CHCl3); H NMR (500 MHz, CDCl3): d
8.18 (br-ddd, 1H, J ¼ 1.7 Hz, ArH), 7.86 (br-dt, 1H, J ¼ 1.4 and 8.0 Hz,
ArH), 7.78 (br-dt, 1H, J ¼ 1.2. 2.0 and 8.0 Hz, ArH), 7.24–7.38 (m, 20H,
ArH), 7.17 (dt, 1H, J ¼ 1.7 and 7.5 Hz, ArH), 7.20 (t, 1H, J ¼ 8.0 Hz, ArH),
4.94 (d, 1H, Jgem ¼ 11.5 Hz, ArCH2-), 4.69–4.81 (m, 4H, ArCH2-), 4.67 (d,
1H, J1,2 ¼ 9.4 Hz, H-1), 4.60 (d, 1H, Jgem ¼ 11.5 Hz, ArCH2-), 4.46 (d, 1H,

16
H. DOHI ET AL.
Jgem ¼ 11.5 Hz, ArCH2-), 4.41 (d, Jgem ¼ 11.7 Hz, 1H, ArCH2-), 3.98 (br-d,
1H, J3,4 ¼ J4,5 ¼ 2.6 Hz, H-4), 3.91 (t, 1H, J ¼ 9.5 Hz, H-2), 3.83 (s, 3H,
CH3OCOAr), 3.59–3.66 (m, 4H, H-3, H-5, H-6a and H-6b); 13C NMR
(125 MHz, CDCl3): d 166.59, 138.78, 138.30, 138.27, 137.96, 135.99, 134.96,
132.44, 130.78, 128.98, 128.58, 128.56, 128.49, 128.34, 128.05, 127.94,
127.92, 127.84, 127.70, 127.67, 87.55, 84.24, 77.48, 76.90, 75.87, 74.61,
73.73, 73.56, 72.83, 68.82, 52.28; HRESIMS: Calcd for C42H46O7NS
[M þ NH4]þ 708.2989; found 708.2985.
4-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-D-
galactopyranoside (5)
To a solution of compound 10 (2.34 g, 4.69 mmol) in MeOH (40 mL) was
added NaOMe (13 mg, 0.22 mmol), and the reaction mixture was stirred at
rt for 4 h. The reaction was quenched by addition of Amberlite ion-
exchange resin and the mixture was filtered. The filtrate was concentrated
and the residue was coevaporated with toluene under diminished pressure.
To a solution of the residue in DMF (50 mL) were added NaH (1.13 g,
28.1 mmol) and BnBr (3.36 mL, 28.1 mmol) slowly at 0 ꢁC, and the reaction
mixture was stirred at rt for 19 h. The reaction was quenched by addition
of MeOH, and EtOAc was added to the mixture. The organic layer was
washed with brine, dried over MgSO4, and concentrated under reduced
pressure. The residue was purified by chromatography (silica gel,
toluene:EtOAc ¼ 50:1) to give compound 5 (5.43 g, 63% over 2 steps) as a
1
white powder; [a]D ꢂ16.8 (c 1.08, CHCl3); H NMR (500 MHz, CDCl3): d
7.81 (br-dt, 2H, J ¼ 2.0 and 8.9 Hz, ArH), 7.56 (br-dt, 2H, J ¼ 1.7 and
8.6 Hz, ArH), 7.25–7.36 (m, 20H, ArH), 4.97 (d, 1H, Jgem ¼ 11.2 Hz,
ArCH2-), 4.70–4.76 (m, 5H, H-1 and ArCH2-), 4.60 (d, 1H, Jgem ¼ 11.5 Hz,
ArCH2-), 4.49 (d, 1H, Jgem ¼ 11.5 Hz, ArCH2-), 4.43 (d, 1H, Jgem
¼
11.7 Hz, ArCH2-), 3.97–4.01 (m, 2H, H-2 and H-4), 3.90 (s, 3H,
CH3OCOAr), 3.60–3.66 (m, 4H, H-3, H-5, H-6a and H-6b); 13C NMR
(125 MHz, CDCl3): d166.86, 141.27, 138.68, 138.25, 138.16, 137.88, 130.00,
129.48, 128.58, 128.48, 128.42, 128.40, 128.07, 127.98, 127.94, 127.86,
127.74, 127.67, 86.50, 84.18, 77.59, 77.42, 75.86, 74.68, 73.75, 73.55, 72.83,
68.84, 52.15; HRESIMS: Calcd for C42H46O7NS [M þ NH4]þ 708.2989;
found 708.2990.
2-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-b-D-
galactopyranoside (6)
To a solution of compound 8 (1.00 g, 2.01 mmol) in MeOH (10 mL) was
added NaOMe (11 mg, 0.2 mmol), and the reaction mixture was stirred at

JOURNAL OF CARBOHYDRATE CHEMISTRY
17
rt for 2 h. The reaction was quenched by addition of Amberlite ion-
exchange resin and filtered, and toluene was added to the filtrate. The solu-
tion was concentrated under reduced pressure and the residue was dis-
solved in pyridine (20 mL). Benzoyl chloride (1.11 mL, 9.65 mmol) was
gradually added to the solution at 0 ꢁC and the reaction mixture was stirred
at rt for 12 h. The reaction was quenched by addition of an excess amount
of MeOH, and the mixture was repeatedly azeotroped with toluene. The
residue was dissolved in CHCl3 and the organic layer was successively
washed with 1N HCl aq, sat. aq. NaHCO3 and brine, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified by
chromatography (silica gel, toluene:EtOAc ¼ 100:1) to give compound 6
1
(1.44 g, 96% over 2 steps) as a white solid; [a]D þ130.7 (c 1.11, CHCl3); H
NMR (500 MHz, CDCl3): d 7.21–8.08 (m, 24H, ArH), 6.06 (br-d, 1H,
J ¼ 2.7 Hz, H-4), 5.91 (t, 1H, J1,2 ¼ J2,3 ¼ 9.9 Hz, H-2), 5.66 (dd, 1H, J2,3
¼
9.9 Hz, J3,4 ¼ 3.4 Hz, H-3), 5.22 (d, 1H, J1,2 ¼ 10.1 Hz, H-1), 4.63 (dd, 1H,
J5,6a ¼ 7.4 Hz, Jgem ¼ 11.4 Hz, H-6a), 4.52 (dd, 1H, J5,6b ¼ 5.2 Hz, Jgem
¼
11.4 Hz, H-6b), 4.47 (br-t, 1H, H-5), 3.64 (s, 3H, CH3OCOAr); 13C NMR
(125 MHz, CDCl3): d 166.95, 166.18, 165.63 ꢃ 2, 165.17, 136.10, 133.83,
133.50, 133.46, 133.41, 132.25, 131.61, 130.74, 130.39, 130.16, 129.98,
129.95, 129.91, 129.52, 129.26, 129.01, 128.79, 128.61, 128.46, 128.43,
126.58, 85.16, 77.36, 75.37, 73.07, 68.51, 67.72, 62.85, 52.16; HRESIMS:
Calcd for C42H38O11NS [M þ NH4]þ 764.2160; found 764.2146.
2-(Methoxycarbonyl)phenyl 2,3,4,6-tetra-O-benzoyl-1-thio-b-D-
glucopyranoside (7)
To a solution of compound 11 (0.69 g, 1.39 mmol) in MeOH (7 mL) was
added NaOMe (7.6 mg, 0.14 mmol), and the reaction mixture was stirred at
rt for 3 h. The reaction mixture was added Amberlite ion-exchange resin
and filtered, and to the filtrate was added toluene. The solution was con-
centrated under reduced pressure and the residue was dissolved in pyridine
(14 mL). Benzoyl chloride (0.77 mL, 6.67 mmol) was gradually added to the
solution at 0 ꢁC and the reaction mixture was stirred at rt for 12 h. The
reaction was quenched by addition of an excess amount of MeOH, and the
mixture was repeatedly azeotroped with toluene under reduced pressure.
The residue was dissolved in CHCl3 and the organic layer was successively
washed with 1N HCl aq, sat. aq. NaHCO3 and brine, dried over MgSO4,
and concentrated under reduced pressure. The residue was purified by
chromatography (silica gel, toluene:EtOAc ¼ 100:1) to give compound 4
(954 mg, 92% over 2 steps) as a white solid: [a]D þ17.8 (c 1.07, CHCl3);
1H NMR (500 MHz, CDCl3): d 7.11–8.05 (m, 24H, ArH), 5.98 (t, 1H, J2,3
J3,4 ¼ 9.4 Hz, H-3), 5.62 ꢂ 5.69 (m, 2H, H-2 and H-4), 5.21 (d, 1H, J1,2
¼
¼

18
H. DOHI ET AL.
10.1 Hz, H-1), 4.69 (dd, 1H, J5,6a ¼ 2.7 Hz, Jgem ¼ 12.1 Hz, H-6a), 4.50 (dd,
1H, J5,6b ¼ 6.5 Hz, Jgem ¼ 12.1 Hz, H-6b), 4.29 (ddd, 1H, J4,5 ¼ 9.7 Hz, J5,6a
¼ 2.7 Hz, J5,6b ¼ 6.5 Hz, H-5), 3.63 (s, 3H, CH3OCOAr); 13C NMR
(125 MHz, CDCl3): d 166.90, 166.15, 165.86, 165.35, 165.05, 136.22, 133.66,
133.38, 132.24, 131.46, 130.63, 130.10, 130.01, 129.98, 129.90, 129.85,
129.63, 129.15, 128.78, 128.71, 128.57, 128.53, 128.40, 126.56, 85.18, 76.44,
74.20, 70.35, 69.57, 63.51, 52.12; HRESIMS: Calcd for C42H38O11NS
[M þ NH4]þ 764.2160; found 764.2129.
General procedures for glycosylation
Powder-type molecular sieves 4Å (ca. 10% of the solvent) was activated in
preliminary dried eggplant-type flasks under reduced pressure at 170 ꢁC for
2 h. After cooling to rt, an adequately dried mixture of glycosyl donor and
acceptor, in a solvent (100 mM) under an argon atmosphere, was added to
the flask through a cannula. After stirring at ambient temperature for
30 min, the mixture was cooled to a target temperature. A promotor was
added to the mixture, and the reaction mixture was stirred until the glyco-
syl acceptor or donor was consumed. Reactions was quenched after con-
sumption of glycosyl acceptor or donor. When both glycosyl acceptor and
donor remained, the reaction was continued up to 48 h and quenched.
After quenching by addition of triethylamine, and the mixture was filtered
through a pad of Celite. The filtrate was diluted with ethyl acetate, and the
organic layer was washed with satd. aq. NaHCO3 and brine, dried over
Na2SO4, filtered and concentrated under reduced pressure. The residue was
subjected to gel partition chromatography (Bio-Beads S-X3, Bio-Rad
Laboratories, Inc., toluene:ethyl acetate ¼ 3:1), and the fractions containing
glycosylated compounds were collected. After concentration of the com-
bined fractions under reduced pressure, the residue was dried under vac-
uum to allow calculation of the yield. The a/b ratio for the glycosylation
was estimated from the integration value originating from each anomer in
1
the H NMR spectrum of the residue. The NMR spectra of all obtained dis-
accharides, including methyl (galactopyranosyl)glucopyranosides[25,26] and
(glucopyranosyl)glucopyranosides[27], were consistent with those in the
literatures.
Acknowledgements
All NMR and MS spectra were obtained at the Center for Analytical Instrumentation,
Chiba University, Japan.

JOURNAL OF CARBOHYDRATE CHEMISTRY
19
Author contributions
The manuscript was written through contributions of all authors./All authors have given
approval to the final version of the manuscript.
Funding
This work was partially supported by a Grant-in-Aid for Young Scientists (B) [25870140]
and Grant-in-Aid for Scientific Research (C) [25450146] from the Ministry of Education,
Culture, Sports, Science, and Technology (MEXT).
ORCID
Hirofumi Dohi
http://orcid.org/0000-0001-9087-995X
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