Useful approach to the synthesis of aryl thio- and selenoglycosides in the presence of rongalite

Article abstract of DOI:10.1016/j.carres.2014.07.011

A simple, mild, and cost effective methodology has been developed for the synthesis of aryl thio-and selenoglycosides from glycosyl halides and diaryl dichalcogenides. Diaryl dichalcogenides undergo reductive cleavage in the presence of rongalite (HOCH₂SO₂Na) to generate a chalcogenide anion in situ followed by reaction with glycosyl halides to furnish the corresponding aryl thio- and selenoglycosides in excellent yields. Using this protocol, synthesis of 4-methyl-7-thioumbelliferyl-β-d-cellobioside (MUS-CB), a fluorescent non-hydrolyzable substrate analogue for cellulases has been achieved.

Full text of DOI:10.1016/j.carres.2014.07.011

Carbohydrate Research 396 (2014) 48–53
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Useful approach to the synthesis of aryl thio- and selenoglycosides
in the presence of rongalite
⇑
Cheerladinne Venkateswarlu, Vibha Gautam, Srinivasan Chandrasekaran
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 June 2014
Received in revised form 15 July 2014
Accepted 15 July 2014
Available online 21 July 2014
A simple, mild, and cost effective methodology has been developed for the synthesis of aryl thio-and sele-
noglycosides from glycosyl halides and diaryl dichalcogenides. Diaryl dichalcogenides undergo reductive
cleavage in the presence of rongalite (HOCH2SO2Na) to generate a chalcogenide anion in situ followed by
reaction with glycosyl halides to furnish the corresponding aryl thio- and selenoglycosides in excellent
yields. Using this protocol, synthesis of 4-methyl-7-thioumbelliferyl-b-
D-cellobioside (MUS-CB), a
fluorescent non-hydrolyzable substrate analogue for cellulases has been achieved.
Keywords:
Thioglycoside
Ó 2014 Elsevier Ltd. All rights reserved.
Phenyl selenoglycoside
Diaryl dichalcogenide
Rongalite
Reductive cleavage
Thioglycosides play a vital role as glycosyl donors for the syn-
thesis of oligosaccharides.1–4 The potential ability of thioglycosides
as activators toward various reagents4 makes them attractive and
stable glycosyl donors. Moreover, the exceptional stability of thio-
glycosides is useful in medicinal and biochemical applications.5 In
the literature, a number of methods are available for the synthesis
of thioglycosides.6–18,20–24 Most commonly, the synthesis of
thioglycosides involves the treatment of peracetylated sugars with
the appropriate thiol in the presence of a Lewis acid or bases.7–12
The other methods include the generation of nucleophilic thiolate
anion in situ from disulfides using Zn dust/ZnCl213 or Lewis acids14
during the reaction with glycosyl halides or peracetylated sugars
and the reaction of S-glycosyl isothiouronium intermediates with
alkyl halides in the presence of a mild base.10,15,16 Despite the use-
fulness of the above methods, they have limitations such as the use
of foul smelling thiols, use of expensive reagents, long reaction
times, lower yields, and harsh reaction conditions. In this context,
developing a convenient and green method would be of greater
importance. From our laboratory, we reported earlier that rongalite
(HOCH2SO2Na), 1 is a useful reagent for the cleavage of diaryl
dichalcogenides to generate the corresponding chalcogenide anion
in situ and it has been utilized for the ring opening of aziridines
and epoxides.17 Rongalite, 1 is a cheap and commercially available
reagent and is used in many organic transformations.18 The
advantage of rongalite, 1 over the other reducing agents includes
its cost effectiveness, mild reaction conditions, and simple work
up procedure. In continuation of our study to explore the
scope and limitation on the use of this reagent, we anticipated that
the in situ generated organo chalcogen anion from diaryl
dichalcogenides and rongalite, 1 can be used in reaction with
glycosyl halides (Scheme 1) to furnish the corresponding thio-
and selenoglycosides.
Accordingly, a reaction was carried out with 2,3,4,6-tetra-
O-acetyl-a-D-glucopyranosyl bromide 2a and diphenyl disulfide
3a in the presence of rongalite 1. Addition of 2a (1 equiv) to a
well-stirred solution of diphenyl disulfide 3a (0.5 equiv), potassium
carbonate (2 equiv), and rongalite 1 (3 equiv)19 in N,N-dimethyl-
formamide (DMF) at room temperature resulted in the formation
of the corresponding phenyl thioglycoside 4a (1 h) in 93% yield.
The stereochemical outcome of the reaction was confirmed by
NMR spectroscopy. The 1H NMR of the product 4a showed a dou-
blet at d 4.71 for H-1, with J1,2 ꢀ 10.0 Hz and the signal at d 5.23
(t, J2,3 ꢀ 10.0 Hz) for H-2 which clearly demonstrated that the
product 4a has a 1,2-trans configuration without any 1,2-cis link-
age. The mechanism of the reaction involves the base promoted
decomposition of rongalite to form formaldehyde and HSOꢁ2 .17
The HSOꢁ2 transfers a single electron to disulfide 3a to form a thio-
late ion in situ which reacts at the anomeric carbon (C-1) of 2a in
an SN2 fashion to give the desired product 4a with 1,2-trans
configuration.
After the successful synthesis of thioglycoside 4a, we decided to
extend the scope of the method with other disulfides 3b–3f using
⇑
Corresponding author. Tel.: +91 80 22932404; fax: +91 80 23600529.
E-mail address: scn@orgchem.iisc.ernet.in (S. Chandrasekaran).
http://dx.doi.org/10.1016/j.carres.2014.07.011
0008-6215/Ó 2014 Elsevier Ltd. All rights reserved.

C. Venkateswarlu et al. / Carbohydrate Research 396 (2014) 48–53
49
OAc
ONa
1
( )
OAc
X
Ar
HO
S
O
,
Ar
X
O
O
AcO
AcO
AcO
AcO
X
Ar
OAc
K2CO3, DMF, rt
OAc
Br
X = S, Se
Ar = Aryl
Scheme 1. General scheme for the synthesis of aryl thioglycosides and selenoglycosides.
2a as the partner. In all the cases the corresponding thioglycosides
4b–4f, respectively, were obtained in good to excellent yields. The
results are summarized in Table 1.
yields (Table 2, entries 2, 3, 6) under similar conditions described
in Scheme 3. The glucosamine derived glycosyl chloride 2e took
1 h to form the corresponding thioglycoside 4k in 83% yield
(Table 2, entry 5) whereas the glycosyl bromide 2d having bromine
at C-6 furnished the desired product 4j in 89% yield after 3 h
(Table 2, entry 4).
Like diaryl disulfides, diphenyl diselenide 3h also showed the
ability to cleave in a reductive fashion with rongalite 1 (Scheme 2).
The reaction of glycosyl halides 2a–2f with diphenyl diselenide 3h
in the presence of rongalite (25 °C) resulted in the formation of the
corresponding selenoglycosides 5a–5f, respectively, in good to
excellent yields. The results are presented in Table 2. While the
glucose, galactose, and lactose derived anomeric bromides 2a–2c,
2f, respectively, reacted with ease (1 h) with diselenide 3h in the
From the Table 1, it can be seen that, irrespective of the nature
of the substituent on the phenyl moiety of the disulfide, the corre-
sponding thioglycosides 4b–4e were obtained in good to excellent
yields (Table 1, entries 1–4). 2,20-Dipyridyl disulfide 3f underwent
reductive cleavage under these conditions followed by its reaction
with 2a to furnish the corresponding thioglycoside 4f in moderate
yield (65%) after 2 h (Table 1, entry 5). However, aliphatic disul-
fides such as dibenzyl disulfide 3g failed to react under these con-
ditions to form the corresponding thioglycoside 4g even after 6 h
(Table 1, entry 6).
Then we further screened the reactivity of 3a with other glyco-
syl halides 2b–2f (Scheme 3). The glycosyl bromides 2b, 2c, and 2f
reacted smoothly (1 h) with 3a in the presence of 1 to form the cor-
responding thioglycosides 4h, 4i, and 4l, respectively, in excellent
presence of
1 (Table 2, entries 1–3, 6). The reaction of
other glycosyl halides 2d and 2e were slower (2–4 h) (Table 2,
entries 4, 5).
Table 1
Synthesis of various thioglycosides 4b–4f derived from 2a
Entry
R–S–S–R (R–)
Time (h)
Thioglycoside
Yield (%)
93
OAc
H3C
O
AcO
AcO
1
1
S
S
3b
OAc
4b
CH3
OAc
MeO
O
AcO
AcO
3c
2
3
4
1
1
2
88
86
79
OAc
OMe
4c
OAc
Cl
O
AcO
AcO
S
S
3d
OAc
Cl
4d
OAc
O2N
O
AcO
AcO
3e
OAc
NO2
4e
OAc
O
N
3f
AcO
AcO
S
S
N
5
6
2
6
65
OAc
4f
OAc
O
AcO
AcO
No reaction
3g
OAc
4g

50
C. Venkateswarlu et al. / Carbohydrate Research 396 (2014) 48–53
Table 2
Synthesis of phenyl thio- and selenoglycosides
Entry
Glycosyl halide
Thio/seleno glycoside
Time (h)
Yield (%)
OAc
OAc
O
O
AcO
AcO
AcO
1
2a
Y = S (4a)
=Se (5a)
1
1
93
86
Y
AcO
Ph
OAc
OAc
Br
OAc
OAc
OAc
OAc
OBn
O
O
2
3
2b
2c
Y = S (4h)
=Se (5b)
1
1
92
86
Y
AcO
AcO
Ph
OAc
OAc
Br
OBn
O
O
BnO
BnO
BnO
BnO
Y = S (4i)
=Se (5c)
1
1
93
82
Y
Ph
OBn
OBn
Br
Br
Ph
Y
O
O
AcO
AcO
4
5
6
2d
2e
2f
Y = S (4j)
=Se (5d)
3
4
89
79
AcO
AcO
OAc
OMe
OAc
OMe
Y
OAc
OAc
O
O
AcO
AcO
AcO
AcO
Y = S (4k)
=Se (5e)
1
2
83
79
Ph
AcHN
OAc
AcHN
OAc
Cl
OAc
AcO
OAc
AcO
OAc
OAc
O
O
O
O
O
AcO
O
AcO
Y = S (4l)
=Se (5f)
1
1
90
83
Y
OAc
OAc
Ph
OAc
OAc
Br
ONa
HO
S
O
OAc
OAc
(1)
O
(3 equiv)
O
S
AcO
S
AcO
AcO
AcO
S
K2CO3 (2 equiv),
DMF,1 h, rt
Ph
OAc
OAc
4a
Br
3a
2a
(0.5 equiv)
Scheme 2. Synthesis of phenyl thioglycoside 4a derived from 2a and 3a.
ONa
HO
S
O
(1)
O
O
(3 equiv)
Ph
Y
X
YPh
RO
RO
Y
Ph
K2CO3 (2 equiv),
DMF, rt
3a
)
Y = S
(
X = Cl or Br
Y = S, Se
3h
Se (
)
Scheme 3. Reaction of glycosyl halides 2 with diphenyl disulfide (3a)/diselenide (3h) in the presence of rongalite 1.
Finally, the synthetic potential of this method has been
demonstrated in the preparation of peracetylated derivative of
4-methyl-7-thioumbelliferyl-b-D-cellobioside 4m which is the
key precursor for MUS-CB, a fluorescent non-hydrolyzable sub-
strate analogue for cellulases.20 Thus treatment of anomeric bro-
mide 2g with disulfide of 3i derived from 7-mercaptocoumarin21
in the presence of rongalite 1 furnished the corresponding peracet-
ylated MUS-CB 4m in excellent yield (86%) with exclusive b-selec-
tivity (Scheme 4). The deacetylation of 4m in the presence of
NaOMe/MeOH furnished MUS-CB.6
In summary, we have presented a useful, alternative approach
to the synthesis of aryl thio- and selenoglycosides. The method

C. Venkateswarlu et al. / Carbohydrate Research 396 (2014) 48–53
51
ONa
HO
S
O
OAc
O
O
S
OAc
O
(1)
AcO
AcO
(3 equiv)
O
2
O
AcO
OAc
K2CO3 (2 equiv),
DMF, 1 h, rt
OAc
Br
2g
3i (0.5 equiv)
OAc
OH
OAc
OH
O
O
O
AcO
AcO
HO
HO
O
O
AcO
Ref. 6
O
HO
S
O
O
S
O
O
OAc
OH
OAc
4m (86%)
Scheme 4. Synthesis of 4-methyl-7-thioumbelliferyl-b-
OH
MUS-CB
D
-cellobioside (MUS-CB).
involves the reductive cleavage of diaryl dichalcogenides using
rongalite to generate the chalcogenide anion in situ which reacts
with glycosyl halides. The significance of this method is its cost
effectiveness and avoiding the use of foul smelling organo
chalcogenols.
1.2.1. Phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-
D
-glucopyranoside
(4a)11,15
25
Yield 93%; white solid; mp: 111–113 °C; [
a
]
ꢁ20.9 (c 0.8,
D
CHCl3); FTIR (neat): 1746 (s), 1440 (w), 1372 (m), 1254 (m),
1226 (s), 1088 (w), 1043 (m), 913 (w), 743 (w) cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 7.51–7.49 (m, 2H), 7.33–7.30 (m, 3H), 5.23
(t, J = 9.3 Hz, 1H), 5.01 (t, J = 9.3 Hz, 1H), 4.98 (t, J = 10.0, 1H), 4.71
(d, J = 10.1, 1H), 4.25–4.16 (m, 2H), 3.75–3.71 (m, 1H), 2.09–1.99
(4s, 12H); 13C NMR (100 MHz, CDCl3): d 170.6, 170.2, 169.4,
169.3, 133.2, 131.7, 129.0, 128.5, 85.8, 75.8, 74.0, 70.0, 68.2, 62.2,
20.8, 20.8, 20.6; HRMS (ESI-TOF) m/z: calcd for C20H24O9SNa
(M+Na)+: 463.1039; found: 463.1035.
1. Experimental section
1.1. General information
All the reactions were performed in an oven dried apparatus
and stirred magnetically. Chemicals and solvents were either
purchased or purified by standard techniques. Analytical TLC was
performed on commercial plates coated with silica gel GF254
(0.25 mm). Silica gel (230–400 mesh) was used for column
chromatography. Melting point values reported are uncorrected.
Infrared spectra were recorded using the JASCO FTIR instrument
and the frequencies are reported in wave numbers (cmꢁ1) and
intensities of the peaks are denoted as s (strong), w (weak), m
(medium), broad (br). 1H and 13C NMR spectra were recorded on
a Jeol 400 MHz (100 MHz, 13C) NMR spectrometer and calibrated
using tetramethylsilane (TMS) for (1H) or residual undeuterated
solvent (CDCl3) as an internal reference. Chemical shifts are
reported in parts per million and multiplicity is indicated using
the following abbreviations: s (singlet), d (doublet), t (triplet), q
(quartet), m (multiplet), bs (broad singlet) etc. Coupling constants
are reported wherever it is necessary in Hertz (Hz). High-
resolution mass spectra (HRMS) were recorded on micromass
Q-TOF electrospray.
1.2.2. 4-Tolyl-phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside (4b)1,11
25
Yield 93%; white solid; mp: 115–117 °C; [
a]
ꢁ19.0 (c 1.0,
D
CHCl3); FTIR (KBr): 3449 (s), 1750 (s), 1382 (w), 1228 (s), 1041
(m) cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.39 (d, J = 8.0, 2H), 7.13
;
(d, J = 7.9 Hz, 2H), 5.21 (t, J = 9.4 Hz, 1H), 5.03 (t, J = 9.8 Hz, 1H),
4.94 (t, J = 9.6 Hz, 1H), 4.64 (d, J = 10.0 Hz, 1H), 4.24–4.16 (m,
2H), 3.73–3.68 (m, 1H), 2.35–1.99 (5s, 15H); 13C NMR (100 MHz,
CDCl3): d 170.7, 170.3, 169.5, 169.3, 138.9, 133.9, 129.7, 127.5,
85.8, 75.8, 74.0, 69.9, 68.2, 62.2, 21.2, 20.8, 20.8, 20.6, 20.6; HRMS
(ESI-TOF) m/z: calcd for C21H26O9SNa (M+Na)+: 477.1195; found:
477.1196.
1.2.3. 4-Methoxy-phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside (4c)11
25
Yield 88%; white solid; mp: 95–97 °C; [
a]
D
ꢁ47.6 (c 2.6,
CHCl3); FTIR (KBr): 1749 (s), 1592 (w), 1495 (w), 1384 (m), 1287
(m), 1226 (s), 1037 (s), 920 (w), 832 (m), 605 (w) cmꢁ1 1H NMR
;
1.2. General procedure for the synthesis of aryl thio- and
selenoglycosides
(400 MHz, CDCl3): d 7.44 (d, J = 8.7 Hz, 2H), 6.85 (d, J = 8.7 Hz,
2H), 5.19 (t, J = 9.4 Hz, 1H), 4.99 (t, J = 9.8 Hz, 1H), 4.89 (t,
J = 9.6 Hz, 1H), 4.56 (d, J = 10.0 Hz, 1H), 4.19 (bs, 2H), 3.81 (s, 3H),
3.69–3.66 (m, 1H), 2.11–1.98 (4s, 12H); 13C NMR (100 MHz,
CDCl3): d 170.5, 170.2, 169.4, 169.2, 160.4, 136.5, 120.9, 114.4,
85.6, 75.7, 74.0, 69.8, 68.1, 62.0, 55.3, 20.8, 20.7, 20.6, 20.5; HRMS
(ESI-TOF) m/z: calcd for C21H26O10SNa (M+Na)+: 493.1144; found:
493.1146.
To a well stirred solution of the aryl disulfides/diphenyl disele-
nide (0.2 mmol, 0.5 equiv) in DMF (2 mL), was added rongalite 1
(1.2 mmol, 3 equiv) and K2CO3 (0.8 mmol, 2 equiv). The reaction
mixture was stirred for 10 min at 25 °C followed by the addition
of glycosyl halide (0.4 mmol, 1 equiv) and stirring was continued.
The completion of the reaction was monitored by TLC till the
consumption of disulfides/diselenide. Then the reaction mixture
was quenched with water and extracted with ethyl acetate
(20 mL ꢂ 2). The organic layer was separated, then washed with
brine, extracted with ethyl acetate (5 mL ꢂ 2), and dried over
anhydrous Na2SO4. The solvent was evaporated under vacuum
and the crude product was purified by column chromatography
on silica gel (230–400 mesh) using ethyl acetate/petroleum ether
as eluent.
1.2.4. 4-Chlorophenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside (4d)11
22
Yield 86%; white solid; mp: 112–114 °C; [
a]
ꢁ41.1 (c 4.3,
D
CHCl3); FTIR (KBr): 3293 (m), 2234 (m), 1751 (s), 1610 (w), 1382
(w), 1225 (s), 1167 (w), 1040 (m), 919 (w), 836 (w) cmꢁ1 1H
NMR (400 MHz, CDCl3): 7.44 (d, J = 8.3 Hz, 2H), 7.29 (d,
J = 8.5 Hz, 2H), 5.22 (t, J = 9.3 Hz, 1H), 5.02 (t, J = 9.8 Hz, 1H), 4.94
;
d

52
C. Venkateswarlu et al. / Carbohydrate Research 396 (2014) 48–53
(t, J = 9.6 Hz, 1H), 4.65 (d, J = 10.0 Hz, 1H), 4.21–3.70 (m, 3H), 2.09–
1.99 (4s, 12H); 13C NMR (100 MHz, CDCl3): d 170.5, 170.1, 169.3,
169.2, 134.9, 129.4, 129.0, 85.1, 75.8, 73.8, 69.7, 68.0, 62.0, 20.7,
20.5; HRMS (ESI-TOF) m/z: calcd for C20H23ClO9SNa (M+Na)+:
497.0649; found: 497.0643.
4.00–3.95 (m, 1H), 3.39 (s, 3H), 3.11 (dd, J = 13.4, 6.7 Hz, 1H),
3.02 (dd, J = 13.7, 8.5 Hz, 1H), 2.06–2.00 (3s, 9H); 13C NMR
(100 MHz, CDCl3): d 170.1, 170.0, 169.8, 136.1, 129.4, 129.0,
126.3, 96.4, 72.0, 70.9, 70.0, 68.2, 55.2, 35.8, 20.7, 20.6; HRMS
(ESI-TOF) m/z: calcd for C19H24O8SNa (M+Na)+: 435.1090; found:
435.1090.
1.2.5. 4-Nitro-phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside (4e)6
Yield 79%; yellow solid; mp: 180–182 °C; [
CHCl3); FTIR (KBr): 3448 (w), 1754 (s), 1737 (s), 1515 (m), 1373
1.2.10. Phenyl 2-acetamido-3,4,6-tri-O-acetyl-1,2-di-deoxy-1-
D
-glucopyranoside (4k)26
22
a
]
D
ꢁ54.4 (c 3.0,
thio-b-
Yield 83%; white solid; mp: 195–197 °C; [
CHCl3); FTIR (KBr): 3304 (w), 1750 (s), 1662 (m), 1559 (w), 1543
22
a]
D
ꢁ14.1 (c 4.3,
(m), 1341 (m), 1242 (s), 1221 (s), 1093 (m), 1044 (s), 913 (w),
851 (w) cmꢁ1 1H NMR (400 MHz, CDCl3): d 8.17 (d, J = 8.7 Hz,
;
(m), 1375 (m), 1243 (s), 1219 (s), 1087 (w), 1047 (m), 913 (w)
2H), 7.60 (d, J = 8.7 Hz, 2H), 5.28 (t, J = 9.3 Hz, 1H), 5.07 (q,
J = 10.4 Hz, 2H), 4.88 (d, J = 10.0 Hz, 1H), 4.26 (dd, J = 12.4, 5.3 Hz,
1H), 4.20 (dd, J = 12.3, 2.0 Hz, 1H), 3.86–3.81 (m, 1H), 2.11–2.01
(4s, 12H); 13C NMR (100 MHz, CDCl3): d 170.4, 170.0, 169.3,
169.2, 147.0, 141.7, 131.0, 123.8, 84.3, 76.1, 73.6, 69.5, 68.0, 62.0,
20.7, 20.6, 20.5; HRMS (ESI-TOF) m/z: calcd for C20H23NO11SNa
(M+Na)+: 508.0890, found: 508.0896.
cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.51–7.48 (m, 2H), 7.30–7.28
;
(m, 3H), 6.07 (d, J = 9.1 Hz, 1H), 5.25 (d, J = 9.8 Hz, 1H), 5.05 (d,
J = 9.7 Hz, 1H), 4.89 (d, J = 10.4 Hz, 1H), 4.23–4.14 (m, 2H), 4.05
(q, J = 9.9 Hz, 1H), 3.78 (m, 1H), 2.07–1.98 (4s, 12H); 13C NMR
(100 MHz, CDCl3): d 171.0, 170.6, 170.2, 169.3, 132.5, 132.3,
128.9, 128.0, 86.5, 75.6, 74.0, 68.5, 62.4, 53.2, 23.2, 20.7, 20.7,
20.5; HRMS (ESI-TOF) m/z: calcd for C20H25NO8SNa (M+Na)+:
462.1199; found: 462.1199.
1.2.6. 2-Pyridyl 2,3,4,6-tetra-O-acetyl-1-thio-b-
D
-
glucopyranoside (4f)22
1.2.11. Phenyl 2,3,6-tri-O-acetyI-4-O-(20,30,40,60-tetra-O-acetyl-b-
D-galactopyranosyl)-l-deoxy-l-thio-b-D
-glucopyranoside (4l)11,26
25
Yield 65%; yellow solid; mp: 120–121 °C; [
a
]
D
ꢁ10.2 (c 0.4,
25
CHCl3); FTIR (KBr): 3468 (w), 1752 (s), 1375 (w), 1254 (m), 1225
Yield 90%; white solid; mp: 160-162 °C; [
a]
+35.4 (c 3.6,
D
(s), 1047 (m), 915 (w) cmꢁ1 1H NMR (400 MHz, CDCl3): d 8.45
;
CHCl3); FTIR (KBr): 1750 (s), 1372 (m), 1231 (s), 1049 (m) cmꢁ1
;
(m, 1H), 7.57–7.52 (m, 1H), 7.22 (d, J = 7.6 Hz, 1H), 7.09–7.06 (m,
1H), 5.84 (d, J = 10.4 Hz, 1H), 5.36 (t, J = 9.3 Hz, 1H), 5.25–5.14
(m, 2H), 4.27 (dd, J = 12.4, 4.4 Hz, 1H), 4.10 (dd, J = 12.4, 1.9 Hz,
1H), 3.91–3.87 (m, 1H), 2.04–2.02 (4s, 12H); 13C NMR (100 MHz,
CDCl3): d 170.6, 170.1, 169.5, 169.4, 155.2, 149.6, 136.5, 123.3,
120.8, 81.6, 75.9, 74.1, 69.4, 68.2, 61.9, 20.7, 20.6, 20.6, 20.6; HRMS
(ESI-TOF) m/z: calcd for C19H23NO9SNa (M+Na)+: 464.0991; found:
464.0990.
1H NMR (400 MHz, CDCl3):
d
7.48–7.29 (m, 5H), 5.34 (d,
J = 3.1 Hz, 1H), 5.22 (t, J = 9.1 Hz, 1H), 5.10 (dd, J = 10.2, 8.0 Hz,
1H), 4.95 (dd, J = 10.4, 3.4 Hz, 1H), 4.90 (t, J = 9.6 Hz, 1H), 4.68 (d,
J=10.1 Hz, 1H), 4.54–4.47 (m, 2H), 4.14–4.05 (m, 3H), 3.87 (t,
J = 6.7 Hz, 1H), 3.75 (t, J = 9.5 Hz, 1H), 3.67–3.63 (m, 1H), 2.15–
1.96 (7s, 21H); 13C NMR (100 MHz, CDCl3): d 170.3, 170.2, 170.1,
170.0, 169.7, 169.5, 169.0, 133.0, 131.7, 128.8, 128.3, 101.0, 85.4,
76.1, 73.8, 70.9, 70.6, 70.2, 69.0, 66.6, 62.10, 60.8, 20.8, 20.7, 20.6,
20.4; HRMS (ESI-TOF) m/z: calcd for C32H40O17SNa (M+Na)+:
751.1884; found: 751.1884.
1.2.7. Phenyl 2,3,4,6-tetra-O-acetyl-1-thio-b-
D
-galacto
pyranoside (4h)11,23
Yield 92%; white solid; mp: 61–63 °C; [
a]
26 +4.5 (c 1.9, CHCl3);
1.2.12. Phenyl 2,3,4,6-tetra-O-acetyl-1-seleno-b-D-
D
FTIR (neat): 1751 (s), 1369 (w), 1223 (s), 1082 (w), 1054 (w) cmꢁ1
;
glucopyranoside (5a)14
Yield 86%; white solid; mp: 97–99 °C; [
CHCl3); FTIR (KBr): 1749 (s), 1372 (s), 1253 (w), 1227 (m), 1085
(m), 1044 (s), 910 (w) cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.61
1H NMR (400 MHz, CDCl3): d 7.53–7.51 (m, 2H), 7.33–7.31 (m, 3H),
5.42 (d, J = 3.2 Hz, 1H), 5.25 (t, J = 10.0 Hz, 1H), 5.06 (dd, J = 9.9,
3.3 Hz, 1H), 4.72 (d, J = 10.0 Hz, 1H), 4.19 (dd, J = 11.4, 7.0 Hz,
1H), 4.12 (dd, J = 11.4, 6.2 Hz, 1H), 3.94 (t, J = 6.5 Hz, 1H), 2.12–
1.98 (4s, 12H); 13C NMR (100 MHz, CDCl3): d 170.3, 170.2, 170.0,
169.4, 132.5, 132.4, 128.9, 128.1, 86.6, 74.4, 72.0, 67.2, 67.2, 61.6,
20.8, 20.6, 20.6, 20.5; HRMS (ESI-TOF) m/z: calcd for C20H24O9SNa
(M+Na)+: 463.1039; found: 463.1036.
a
]
D
ꢁ54.5 (c 1.5,
22
;
(d, J = 7.48 Hz, 2H), 7.37–7.28 (m, 3H), 5.19 (t, J = 9.3 Hz, 1H),
5.06 (q, J = 9.6 Hz, 2H), 4.89 (d, J = 10.1 Hz, 1H), 4.20–3.67 (m,
3H), 2.07–1.99 (4s, 12H); 13C NMR (100 MHz, CDCl3): d 170.6,
170.2, 169.4, 169.3, 135.2, 129.0, 128.6, 126.9, 80.9, 76.8, 73.8,
70.7, 68.1, 62.1, 20.8, 20.7, 20.6, 20.5; HRMS (ESI-TOF) m/z: calcd
for C20H24O9SeNa (M+Na)+: 511.0483; found: 511.0485.
1.2.8. Phenyl 2,3,4,6-tetra-O-benzyl-1-thio-b-
D
-glucopyranoside
(4i)24
1.2.13. Phenyl 2,3,4,6-tetra-O-acetyl-1-seleno-b-D-
Yield 93%; pale yellow solid; mp: 88–90 °C; [
a]
D
ꢁ43.2 (c 1.9,
galactopyranoside (5b)14
27
26
CHCl3); FTIR (KBr): 3029 (w), 2904 (w), 1139 (m), 1062 (s), 755 (w),
733 (m), 695 (m) cmꢁ1; 1H NMR (400 MHz, CDCl3): d 7.59–7.57 (m,
2H), 7.40–7.18 (m, 23H), 4.91–4.81 (m, 4H), 4.73 (d, J = 10.2 Hz,
1H), 4.67 (d, J = 9.8 Hz, 1H), 4.62–4.52 (m, 3H), 3.80–3.62 (m,
4H), 3.53–3.49 (m, 2H); 13C NMR (100 MHz, CDCl3): d 138.4,
138.3, 138.0, 133.8, 131.9, 128.9, 128.4, 128.4, 128.3, 128.2,
127.9, 127.8, 127.8, 127.7, 127.6, 127.5, 127.4, 87.4, 86.7, 80.8,
79.1, 77.8, 75.8, 75.4, 75.0, 73.4, 69.0; HRMS (ESI-TOF) m/z: calcd
for C40H40O5SNa (M+Na)+: 655.2494; found: 655.2496.
Yield 86%; gummy mass; [
a]
ꢁ5.3 (c 2.1, CHCl3); FTIR (neat):
1H NMR
D
1750 (s), 1369 (w), 1221 (s), 1081 (w), 1055 (m) cmꢁ1
;
(400 MHz, CDCl3): d 7.64–7.62 (m, 2H), 7.36–7.25 (m, 3H), 5.41
(d, J = 3.2 Hz, 1H), 5.27 (t, J = 10.0 Hz, 1H), 5.02 (dd, J = 9.9, 3.3 Hz,
1H), 4.91 (d, J = 10.1 Hz, 1H), 4.17 (dd, J = 11.3, 6.9 Hz, 1H), 4.10
(dd, J = 11.3, 6.2 Hz, 1H), 3.91 (t, J = 6.6 Hz, 1H), 2.09–1.97 (4s,
12H); 13C NMR (100 MHz, CDCl3): d 170.3, 170.1, 170.0, 169.5,
134.8, 128.9, 128.3, 127.7, 81.8, 75.4, 71.7, 68.0, 67.3, 61.6, 20.8,
20.6, 20.6; HRMS (ESI-TOF) m/z: calcd for
C20H24O9Se+Na
(M+Na)+: 511.0483; found: 511.0485.
1.2.9. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-phenylthio-a-D-
glucopyranoside (4j)25
1.2.14. Phenyl 2,3,4,6-tetra-O-benzyl-1-seleno-b-D-
Yield 89%; gummy mass; [
a
]
D
+162.3 (c 3.4, CHCl3); FTIR
glucopyranoside (5c)24
22
26
(neat): 1750 (s), 1370 (w), 1245 (m), 1123 (s), 1044 (m), 742 (w)
cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.36–7.18 (m, 5H), 5.44 (t,
J = 9.7 Hz, 1H), 4.97 (t, J = 9.6 Hz, 1H), 4.92–4.87 (m, 2H),
Yield 82%; white solid; mp: 77–79 °C; [
CHCl3); FTIR (KBr): 3448 (s), 1664 (s), 1135 (s), 1065 (s), 732 (m),
694 (m) cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.68 (d, J = 7.1 Hz,
a]
ꢁ13.6 (c 0.9,
D
;
;

C. Venkateswarlu et al. / Carbohydrate Research 396 (2014) 48–53
53
2H), 7.39–7.16 (m, 23H), 4.90–4.80 (m, 5H), 4.72 (d, J = 10.1 Hz,
1H), 4.62–4.51 (m, 3H), 3.79–3.63 (m, 4H), 3.54–3.49 (m, 2H);
13C NMR (100 MHz, CDCl3): d 138.3, 138.3, 138.0, 137.9, 134.4,
129.0, 128.5, 128.4, 128.4, 128.3, 128.2, 127.9, 127.8, 127.8,
127.8, 127.7, 127.6, 127.5, 86.8, 82.9, 81.3, 80.1, 77.7, 75.8, 75.2,
75.0, 73.4, 68.9; HRMS (ESI-TOF) m/z: calcd for C40H40O5SeNa
(M+Na)+: 703.1939; found: 703.1935.
4.1 Hz, 1H), 4.13 (dd, J = 12.0, 5.6 Hz, 1H), 4.04 (dd, J = 12.5,
1.7 Hz, 1H), 3.80–3.66 (m, 3H), 2.42–1.99 (6s, 24H); 13C
NMR (100 MHz, CDCl3):
d 170.6, 170.5, 170.3, 169.7, 169.5,
169.4, 169.2, 160.3, 153.6, 151.9, 138.0, 126.4, 124.7, 119.2,
118.3, 115.2, 100.9, 84.7, 77.3, 76.3, 73.5, 73.0, 72.1, 71.6, 69.8,
67.8, 62.1, 61.6, 20.9, 20.8, 20.7, 20.6, 20.5, 18.6; HRMS
(ESI-TOF) m/z: calcd for C36H42O19SNa (M+Na)+: 833.1939; found:
833.1940.
1.2.15. Methyl 2,3,4-tri-O-acetyl-6-deoxy-6-phenylseleno-a-D-
glucopyranoside (5d)
Acknowledgements
26
Yield 79%; gummy mass; [
a]
+143.3 (c 3.3, CHCl3); FTIR
D
(neat): 1755 (s), 1371 (m), 1247 (s), 1224 (s), 1067 (m), 1045 (s),
CVR thanks the CSIR for a Shyama Prasad Mukherjee (SPM)
Senior Research Fellowship, VG thanks the Department of Science
and Technology (DST), New Delhi for a fellowship under the
Women Scientists Programme, and SCN thanks the Department
of Science and Technology (DST) for the award of SERB Distin-
guished Fellow and the JNCASR, Jakkur for the Hindustan Lever
Professorship.
739 (w) cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.51–7.49 (m, 2H),
;
7.28–7.24 (m, 3H), 5.44 (t, J = 9.6 Hz, 1H), 4.97–4.87 (m, 3H),
4.05–4.00 (m, 1H), 3.42 (s, 3H), 3.06–2.97 (m, 2H), 2.07 (s, 3H),
2.00 (2s, 6H); 13C NMR (100 MHz, CDCl3): d 170.1, 170.0, 169.8,
132.6, 130.4, 129.1, 127.1, 96.5, 72.6, 71.0, 70.0, 68.8, 55.4, 29.2,
20.7, 20.7, 20.7; HRMS (ESI-TOF) m/z: calcd for C19H24O8SeNa
(M+Na)+: 483.0534; found: 483.0530.
Supplementary data
1.2.16. Phenyl 2-acetamido-3,4,6-tri-O-acetyl-1,2-di-deoxy-1-
seleno-b-
Yield 79%; pale yellow solid; mp: 194–196 °C; [
CHCl3); FTIR (KBr): 3448 (bs), 1745 (s), 1661 (w), 1375 (w), 1243
(s), 1227 (s), 1046 (m), 738 (w) cmꢁ1 1H NMR (400 MHz, CDCl3):
D
-glucopyranoside (5e)27
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2014.07.
011.
a]D ꢁ29.9 (c 8.8,
;
d 7.62 (d, J = 6.7 Hz, 2H), 7.32–7.26 (m, 3H), 6.15–6.11 (m, 1H),
5.18 (t, J = 9.7 Hz, 1H), 5.07–5.02 (m, 2H), 4.21–4.11 (m, 3H),
3.72–3.68 (m, 1H), 2.05–1.97 (4s, 12H); 13C NMR (100 MHz,
CDCl3): d 170.1, 170.6, 170.2, 169.3, 134.6, 128.9, 128.2, 128.0,
82.6, 73.6, 68.5, 62.4, 53.9, 23.2, 20.7, 20.7, 20.5; HRMS (ESI-TOF)
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510.0645.
C
20H25NO8SeNa (M+Na)+: 510.0643; found:
1.2.17. Phenyl 2,3,6-tri-O-acetyI-4-O-(20,30,40,60-tetra-O-acetyl-b-
D
-galactopyranosyl)-l-deoxy-l-seleno-b-
Yield 83%; white solid; mp: 77–79 °C; [
D
-glucopyranoside (5f)14
23
a]
ꢁ29.6 (c 5.5,
D
CHCl3); FTIR (KBr): 1751 (s), 1371 (m), 1231 (s), 1054 (m), 910
(w) cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.59 (d, J = 7.8 Hz, 2H),
;
7.36–7.27 (m, 3H), 5.34 (d, J = 1.9 Hz, 1H), 5.18 (t, J = 9.0 Hz, 1H),
5.09 (dd, J = 10.1, 8.2 Hz, 1H), 4.96–4.85 (m, 3H), 4.52 (d,
J = 11.8 Hz, 1H), 4.46 (d, J = 7.9 Hz, 1H), 4.14–4.04 (m, 3H), 3.86
(t, J = 6.7 Hz, 1H), 3.73 (t, J = 9.5 Hz, 1H), 3.63–3.59 (m, 1H),
2.14–1.96 (6s, 21H); 13C NMR (100 MHz, CDCl3): d 170.3, 170.2,
170.1, 170.0, 169.7, 169.6, 169.0, 135.2, 128.9, 128.4, 126.9,
100.9, 80.7, 77.7, 76.0, 73.6, 71.1, 70.9, 70.6, 69.0, 66.5, 62.0, 60.7,
20.8, 20.8, 20.7, 20.6, 20.6, 20.5; HRMS (ESI-TOF) m/z: calcd for
14. Sau, A.; Misra, A. K. Synlett 2011, 1905–1911.
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17. Ganesh, V.; Chandrasekaran, S. Synthesis 2009, 3267–3278.
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19. When we decrease the equivalents of rongalite (<3 equiv), we found a gradual
decrease in the yield of the product.
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Biomol. Chem. 2004, 2, 2188–2194.
C
32H40O17SeNa (M+Na)+: 799.1328; found: 799.1326.
1.2.18. (2R,3R,4S,5R,6S)-2-(Acetoxymethyl)-6-{[(2R,3R,4S,5R,6S)-
4,5-diacetoxy-2-(acetoxymethyl)-6-[(4-methyl-2-oxo-2H-
chromen-7-yl)thio]tetrahydro-2H-pyran-3-yl]oxy}tetrahydro-
2H-pyran-3,4,5-triyl triacetate (4m)6
25
Yield 86%; white solid; mp: 205–207 °C; [
a]
ꢁ4.8 (c 1.0,
D
CHCl3); FTIR (KBr): 3481 (br), 2959 (w), 1750 (s), 1604 (w), 1374
25. González, F. S.; Baer, H. H. Carbohydr. Res. 1990, 202, 33–47.
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4623–4625.
(m), 1230 (s), 1168 (w), 1041 (s), 955 (w) cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 7.50 (d, J = 8.6 Hz, 2H), 7.27–7.25 (m, 1H),
6.28 (s, 1H), 5.24 (t, J = 8.9 Hz, 1H), 5.16 (t, J = 9.3 Hz, 1H), 5.07
(t, J = 9.6 Hz, 1H), 5.01–4.92 (m, 2H), 4.81 (d, J = 10.1 Hz, 1H),
4.59 (d, J = 11.7 Hz, 1H), 4.52 (d, J = 8.0 Hz, 1H), 4.38 (dd, J = 12.5,