Glycosylation via mixed disulfide formation using glycosylthio-phthalimides and -succinimides as glycosylsulfenyl-transfer reagents

Article abstract of DOI:10.1016/j.carres.2011.04.020

The silver salts of tetra-O-acetyl α- or -β-d-glycopyranosyl thiols 1a-4a react smoothly with N-bromophthalimide and N-bromosuccinimide to furnish glycosylthio-phthalimide (1b-4b) and -succinimide (1c-3c) derivatives. Reactions of these reagents with alip

Full text of DOI:10.1016/j.carres.2011.04.020

Carbohydrate Research 346 (2011) 1622–1627
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Glycosylation via mixed disulfide formation using glycosylthio-phthalimides
and -succinimides as glycosylsulfenyl-transfer reagents
⇑
Tünde-Zita Illyés, Tamás Szabó, László Szilágyi
Department of Organic Chemistry, University of Debrecen, H-4010 Debrecen Pf. 20, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 24 April 2011
The silver salts of tetra-O-acetyl a- or -b-D-glycopyranosyl thiols 1a–4a react smoothly with N-bromoph-
thalimide and N-bromosuccinimide to furnish glycosylthio-phthalimide (1b–4b) and -succinimide (1c–
3c) derivatives. Reactions of these reagents with aliphatic, aromatic, and glycosyl thiols as well as with
cysteine and glutathione result in the formation of glycosylated mixed disulfides under mild conditions
and in good yields. The S-glycosyl-N-acylsulfenamides described here represent novel, convenient glyco-
sylsulfenyl-transfer reagents in effecting glycosylation of various thiols, including sugars, amino acids
and peptides, through disulfide formation and can, therefore, be useful in controlled glycosylation of
proteins as well.
Dedicated to Professor András Lipták on the
occasion of his 75th birthday
Keywords:
Mixed disulfides
Glycosylsulfenamides
Glycosylsulfenyl-transfer
Glycosyl thiol
Ó 2011 Elsevier Ltd. All rights reserved.
Cysteine
Glutathione
1. Introduction
It has long been known that nucleophilic substitution of
N-phthalyl-S-substituted sulfenamides with thiols results in the
The disulfide linkage has recently gained importance in carbo-
hydrate chemistry as a bonding motif to obtain glycoconjugates
characterized by a highly controlled distribution pattern of sugar
residues attached to the protein surface (for recent reviews,
see:1,2). On the other hand, unsymmetrical diglycosyl disulfides
were synthesized and proposed as novel carbohydrate scaffolds
with potential biological activity.3 Installation of the disulfide link-
age in these derivatives is usually based on the nucleophilic attack
of a thiol (or thiolate) onto a sulfenyl derivative, such as thiosulfo-
nate esters R-S–SO2-R0, containing a divalent electrophilic sulfur.4–
formation of mixed disulfides (Scheme 1).14,15
The method has several advantages: the starting thiophthali-
mides are stable and easy to prepare, the conversion is close to
quantitative in most cases, the by-product phthalimide usually
precipitates from the reaction mixture and only minimal side reac-
tions such as disulfide interchange were observed. Similarly, succi-
nyl sulfenamides can be used16 in place of the phthalyl derivatives.
N-phthalyl- and N-succinyl-S-substituted sulfenamides can be ob-
tained via reaction of phthalimide or succinimide with sulfenyl
chlorides17 or -bromides.18 Sulfenyl halogenides in general and,
glycosylsulfenyl halogenides in particular, are however, unstable,
difficult to purify and, therefore, are often generated in situ and
used without isolation in one-pot reactions with subsequent addi-
tion of the imide reagent. These problems can be obviated by react-
ing N-bromophthalimide or -succinimide with thiols or with
thiolate salts to obtain the desired acylsulfenamides more conve-
niently and in high yields.
6
Other approaches have also been investigated (for leading refer-
ences see:7–9). Thiosulfonate esters of sugars, especially glycosyl
methanethiosulfonates (glyco-MTS10) are occasionally difficult to
prepare and purify, the yields are often moderate to low and
may be unstable especially under basic conditions. The search for
alternative glycosylsulfenyl-transfer reagents with more conve-
nient properties is clearly warranted. Non-sulfonate ester type re-
agents such as glycosyl-aryl disulfides,11 glycosyl selenylsulfides,12
and 1-chlorobenzotriazole-mediated transfer reactions13 were
proposed for such purposes. Here we wish to report on the synthe-
ses of some new sulfenamide type derivatives and testing their gly-
cosylsulfenyl-transfer properties toward carbohydrate-, amino
acid-, peptide- and other thiols.
O
N
O
O
SR
+
R' SH
R
S
S
R'
NH
O
+
⇑
Corresponding author. Fax: +36 52 512 744.
E-mail address: lszilagyi@tigris.klte.hu (L. Szilágyi).
Scheme 1. Disulfide formation via N-phthalyl-S-substituted sulfenamides.
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.04.020

T.-Z. Illyés et al. / Carbohydrate Research 346 (2011) 1622–1627
1623
We have therefore set out to prepare glycosylsulfenyl phthali-
mides and –succinimides for subsequent use in thiol exchange
reactions to obtain various sugar-containing nonsymmetric
disulfides.
(8) or secondary (9) carbons as well as with cysteine (10) and glu-
tathione (11) as models for protein glycosylations (Scheme 3,
Table 2).
These reactions proceeded under mild conditions to provide
glycosyl-ar(alk)yl disulfides (12, 13, entries 1 and 2), nonsymmet-
rical diglycosyl disulfides (14–19, entries 3–8) and glycosyl amino
acid- (20) or -peptide (21) disulfides in good to excellent yields
(Table 2). Remarkably, glycosylated glutathione 21 was obtained
in good yield (entry 10) using unprotected glutathione indicating
that the free amino- and carboxylic functions did not interfere with
the glycosylsulfenyl-transfer reaction. Esterification of the carbox-
ylic function of cysteine proved, however, necessary to ensure rea-
sonable yield of 20 in an analogous reaction (entry 9). The
2. Results and discussion
2.1. Syntheses of S-glycosyl-N-acylsulfenamides (1b–4b and
1c–3c)
Representative phthalimido derivatives 1b–4b were easily ob-
tained by reacting the silver salts of acetylated glycosyl thiols
1a–4a with N-bromophthalimide under mild conditions. The succi-
nyl derivatives 1c–3c were obtained under similar conditions using
the commercially available N-bromosuccinimide reagent (Scheme
2, Table 1)
The starting glycosyl thiols 1a–4a are common, stable deriva-
tives easily prepared (1a,19 2a,20 3a,21,22 4a,23,22) in two high yield-
ing steps from the respective acetohalogeno sugars.
The reactions above quickly proceed to practically full conver-
sion via precipitation of the AgBr from the reaction mixture and
the products 1b–4b, 1c–3c were isolated in fair to good yields (Ta-
ble 1).
The glycosylthio-phthalimide- and -succinimide reagents
(glyco-PTI, glyco-SCI) are more conveniently prepared than the cor-
responding methanethiosulfonates (glyco-MTS10) and the yields are
comparable to those of the recently introduced glycosyl-phenyl-
thiosulfonates (glyco-PTS5). The procedure allows access to glyco-
3
anomeric configurations were trivially deduced from the JH1,H2
values for the gluco configurations. For the mannose disulfides
1
15 and 16 this assignment was based on the JH1,C1 values24–27
(see Section 3).
In summary, the glyco-PTI and glyco-SCI reagents described in
this communication represent efficient and valuable synthons for
the preparation of glycomimetics featuring three-bond, disulfide
interglycosidic connections (for a review, see:30) and are promising
as a novel approach to controlled glycosylations by attachment of
sugars to cysteine side chains of proteins (for recent reviews,
see:1,2).
3. Experimental
3.1. General methods
sylsulfenyl-transfer reagents with either b- or
a-anomeric
configurations (cf. 4a, 4b); this is not the case for the glyco-MTS
or glyco-PTS reagents which are available in b-configurations only.
NMR spectra were recorded on a Bruker Avance DRX 500 (500/
125 MHz for 1H/13C) spectrometer. Chemical shifts are referenced
to internal TMS (1H), or to the residual solvent signals (13C). Mass
spectra were measured using a Bruker micrOTOFQ mass spectrom-
eter. Optical rotations were determined with a Perkin–Elmer 241
polarimeter. A Vario MICRO CUBE instrument was used for ele-
mental analyses. TLC was performed on DC-Alurolle Kieselgel
F254 (Merck), and the plates were visualized under UV light and
by gentle heating. For column chromatography Kieselgel 60
(Merck, particle size 0.063–0.200) was used. N-bromosuccinimide
was purchased from Sigma–Aldrich. N-bromophthalimide was pre-
pared from potassium-phthalimide.31
2.2. Syntheses of mixed glycosyl disulfides
The glycosylsulfenyl-transfer properties of the new glyco-PTI/
glyco-SCI reagents were then tested in reactions with simple ar
(alk)yl thiols (5, 6), monosaccharide thiols bearing thiol functions
either at the anomeric- (1a–3a, 7), or at non-anomeric, primary-
OAc
O
OAc
O
R4
R3
R4
R3
Rb
Ra
Rb
Ra
i)
ii) or iii)
R2
OAc
Ag salts
R2
OAc
3.2. Synthetic procedures
3.2.1. N-Phthalyl-S-(2,3,4,6-tetra-O-acetyl-b-
sulfenamide (1b)
D
-glucopyranosyl)
-gluco-
R1
R1
1a - 4a
1b - 4b
1c 3c
To a stirred solution of 1-thio-2,3,4,6-tetra-O-acetyl-b-
D
-
pyranose 1a (1 g, 2.74 mmol) in 40 mL EtOAc, 0.455 g (2.74 mmol)
AgOAc was added The reaction mixture was stirred at room temper-
ature until TLC indicated consumption of the starting thiol (40 min),
the solution cooled to 0–4 °C and a cold solution of N-bromophthal-
imide (0.62 g, 2.74 mmol) in 20 mL EtOAc was added. After 10 min.
the reaction mixture was filtered through Celite, evaporated under
reduced pressure and the residue crystallized from MeOH to furnish
0.62 g of white solid. Evaporation of the mother liquor provided
Scheme 2. Reagents and conditions: (i) EtOAc, AgOAc (1 equiv), rt, 40 min; (ii)
EtOAc, N-bromophthalimide (1 equiv), 4 °C to rt, 10 min; (iii) EtOAc, N-bromosuc-
cinimide (1 equiv), 4 °C to rt, 10 min.
Table 1
Glycosyl thiols and sulfenamides
Compound
Ra
Rb
R1
R2
R3
R4
Yield (%)
b-Glc
b-Gal
b-Man
1a
H
H
H
H
H
H
H
H
SH
OAc
OAc
OAc
OAc
OAc
OAc
H
H
H
H
H
H
H
H
H
H
H
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
H
H
H
OAc
OAc
OAc
OAc
OAc
H
H
H
OAc
OAc
OAc
H
H
H
—
1b
1c
2a
2b
2c
3a
3b
3c
4a
4b
SNPht
SNSu
SH
SNPht
SNSu
SH
SNPht
SNSu
H
80
65
—
63
50
—
60
58
—
OAc
O
OAc
O
O
S
H
N
S
H
SR'
solvent, rt.
OAc
+
R'-SH
OAc
O
AcO
AcO
H
SH
SNPht
OAc
OAc
a-Man
H
H
H
45
Scheme 3. Syntheses of mixed glycosyl disulfides.

1624
T.-Z. Illyés et al. / Carbohydrate Research 346 (2011) 1622–1627
Table 2
Starting compounds and mixed glycosyl disulfide products
Entry
Sulfenamide reagent
Thiol component
Glycosyl disulfide
Yield (%)
75
Ref.
28
R0
OAc
O
AcO
AcO
1.
1b
5
S
S
S
S
S
OAc
OAc
O
12
1b
1c
72
61
AcO
AcO
2.
28
6
OAc
OAc
O
13
1b
1c
92
85
OAc
OAc
O
AcO
O
AcO
AcO
S
OAc
OAc
3.
4.
29
3
AcO
OAc
OAc
AcO
2a
3a
14
15
1b
1c
93
91
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
S
OAc
OAc
OAc
S
O
OAc
OAc
AcO
OAc
O
AcO
O
AcO
AcO
AcO
S
S
OAc
5.
6.
4b
89
OAc
1a
OAc
OAc
O
OAc
OAc
16
17
1b
1c
89
82
OAc
O
OAc
AcHN
O
AcO
AcO
AcO
AcO
S
OAc
OAc
S
S
O
AcO
NHAc
OAc
7
O
OAc
O
H3C
H3C
AcO
AcO
O
O
OAc
H3C
O
S
O
O
7.
1b
72
O
H3C
CH3
8
H3C
O
O
O
H3C
CH3
18
OBn
OAc
OBn
O
O
O
AcO
AcO
S
S
AcO
AcO
8.
9.
1b
1b
74
65
OAc
OMe
OAc
OAc
OMe
9
19
COOCH3
NH2
COOCH3
NH2
OAc
O
AcO
AcO
S
S
S
10
OAc
20
COOH
O
O
COOH
NH2
OAc
O
AcO
AcO
S
NH2
NH
NH
10.
1b
84
OAc
NH
COOH
NH
COOH
21
O
O
11
another 0.50 g of 1b after purification by column chromatography
(6:4 hexane/EtOAc). Overall yield 1.12 g (80%), mp 172–175 °C,
3.2.2. N-Phthalyl-S-(2,3,4,6-tetra-O-acetyl-b-D-
galactopyranosyl)sulfenamide (2b)
This compound was prepared as described for 1b, starting from
1 g (2.74 mmol) of 1-thio-2,3,4,6-tetra-O-acetyl-b- -galactopyra-
½
a 2D5
ꢀ
ꢁ32.5 (c 0.51, CHCl3); 1H NMR (CDCl3, 500 MHz): d 7.95 (dd,
2H, Aryl-H) 7.82 (dd, Aryl-H); 5.22 (t, 1H, H-3); 5.06 (t, 1H, H-2,
J3,4 9.0 Hz); 4.98 (t, 1H, H-4); 4.68 (d, 1H, H-1, J1,2 10.1 Hz); 4.18
(dd, 1H, H-6a, J6a,6b 12.1 Hz, J5,6a 5.0 Hz); 4.09 (dd, 1H, H-6b, J5,6b
2.3 Hz); 3.67 (m, 1H, H-5); 2.19, 2.01, 2.00, 1.96 (s, 12H, 4 ꢂ COCH3);
13C NMR (CDCl3, 125 MHz): d 170.4, 169.9, 169.7, 169.2 (COCH3);
167.2 (CO); 134.8, 131.8, 124.0 (Aryl-C) 87.2 (C-1); 75.9 (C-5);
73.6 (C-3); 68.9 (C-2); 67.8 (C-4); 61.8 (C-6); 20.6, 20.5, 20.4
(COCH3). Anal. Calcd for C22H23NO11S: C, 51.87; H, 4.52; N, 2.75; S,
6.29. Found: C, 51.83; H, 4.78; S, 6.31; N, 2.80; HRMS m/z Calcd for
D
nose 2a. Overall yield 0.88 g (63%) of a white powder, mp 157–
159 °C, ½a 2D5
ꢀ
ꢁ40.6 (c 0.50, CHCl3); 1H NMR (CDCl3, 500 MHz): d
7.96 (dd, 2H, Aryl-H), 7.82 (dd, 2H, Aryl-H); 5.39 (d, 1H, H-4);
5.24 (t, 1H, H-2); 5.06 (dd, 1H, H-3, J3,4 3.2 Hz); 4.70 (d, 1H, H-1,
J1,2 10.1 Hz); 4.08 (dd, 2H, H-6a,b, J6a,6b 11.3 Hz, J5,6a 6.8 Hz); 3.84
(m, 1H, H-5); 2.21, 2.13, 1.99, 1.91 (s, 12H, 4 ꢂ COCH3); 13C NMR
(CDCl3, 125 MHz): d 170.1, 170.0, 169.8 (COCH3); 167.2 (CO);
134.8, 131.8, 123.9 (Aryl-C); 88.6 (C-1); 74.4 (C-5); 71.5 (C-3);
66.8 (C-2); 66.0 (C-4); 61.1 (C-6); 20.7, 20.5, 20.4, 20.3 (COCH3).
C
22H23NO11S [M+Na]+: 532.0884. Found: 532.0879.

T.-Z. Illyés et al. / Carbohydrate Research 346 (2011) 1622–1627
1625
Anal. Calcd for C22H23NO11S: C, 51.87; H, 4.52; N, 2.75; S, 6.29.
NMR (CDCl3, 500 MHz): d 5.38 (d, 1H, H-4, J3,4 2.8 Hz); 5.14 (t,
1H, H-2, J1,2 10.1 Hz); 5.05 (dd, 1H, H-3, J2,3 9.9 Hz); 4.69 (d, 1H,
H-1); 4.11 (dd, 2H, H-6a, J6a,6b 11.3 Hz, J5,6a 6.4 Hz); 3.86 (t, 1H,
H-5); 2.85 (s, 4H, CH2), 2.12, 2.08, 2.02, 2,00 (s, 12H, 4 ꢂ OCOCH3);
13C NMR (CDCl3, 125 MHz): d (CH2CO); 170.5, 169.7, 169.5, 169.1
(OCOCH3); 89.1 (C-1); 75.7 (C-5); 73.1 (C-3); 68.2 (C-2); 68.4 (C-
4); 62.8 (C-6); 28.5 (CH2); 22.6, 22.4 (OCOCH3). Anal. Calcd for
Found: C, 51.71; H, 4.49; N, 2.74; S, 6.24. HRMS m/z Calcd for
C
22H23NO11S [M+Na]+: 532.0884. Found: 532.0864.
3.2.3. N-Phthalyl-S-(2,3,4,6-tetra-O-acetyl-b-D-
mannopyranosyl)sulfenamide (3b)
Starting from 0.5 g (1.37 mmol) of 1-thio-2,3,4,6-tetra-O-acetyl-
-mannopyranose 3a, the procedure described for 1b provided
b-D
C18H23O11SN: C, 46.85; H, 5.02; S, 6.95; N, 3.04. Found: C, 47.40;
0.42 g (60%) of 3b after purification by column chromatography
H, 5.11; S, 6.57; N, 3.08.
(6:4 hexane/EtOAc). White powder, mp 164–167 °C; ½a D25
ꢁ63.6 (c
ꢀ
0.50, CHCl3); 1H NMR (CDCl3, 500 MHz): d 7.96 (dd, 2H, Aryl-H),
7.81 (dd, 2H, Aryl-H); 5.69 (dd, 1H, H-2, J1,2 1.2 Hz, J2,3 3.5 Hz);
5.26 (t, 1H, H-4, J3,4 10.0 Hz) 5.04 (dd, 1H, H-3); 5.01 (s, 1H, H-1);
4.26 (dd, 1H, H-6a, J6a,6b 12.0 Hz, J5,6a 6.1 Hz); 4.07 (dd, 1H, H-6b,
J5,6b 2.7 Hz); 3.62 (m, 1H, H-5); 2.24, 2.03, 2.00, 1.96 (s, 12H,
4 ꢂ COCH3); 13C NMR (CDCl3, 125 MHz): d 170.4, 170.0, 169.8,
169.4 (COCH3); 167.2 (CO); 134.8, 131.9, 124.1 (Aryl-C), 85.2 (C-
1); 76.4 (C-5); 71.4 (C-3); 68.8 (C-2); 65.6 (C-4); 62.5 (C-6); 20.5,
20.2 (COCH3). Anal. Calcd for C22H23NO11S: C, 51.87; H, 4.52; N,
2.75; S, 6.29. Found: C, 51.83; H, 4.76; N, 2.83; S, 6.35. HRMS m/z
Calcd for C22H23NO11S [M+Na]+: 532.0884. Found: 532.0870.
3.2.7. N-Succinyl-S-(2,3,4,6-tetra-O-acetyl-b-D-
mannopyranosyl)sulfenamide (3c)
Compound 3c was prepared as described for 1c, starting from
0.50 g (1.37 mmol) of 3a. Syrup (after column chromatography,
1:1 hexane/EtOAc), 0.36 g, (58%). ½a D25
ꢀ
ꢁ24.3 (c 0.75, CHCl3); 1H
NMR (CDCl3, 500 MHz): d 5.54 (dd, 1H, H-2, J2,3 3.6 Hz); 5.22 (t,
1H, H-4, J3,4 9.8 Hz); 5.06 (dd, 1H, H-1, J1,2 1.2 Hz); 5.02 (dd, 1H,
H-3); 4.22 (dd, 1H, H-6a, J6a,6b 12.3 Hz, J5,6a 5.5 Hz); 4.08 (dd, 1H,
H-6b, J5,6b 3.0 Hz) 3.62 (m, 1H, H-5); 2.83 (s, 4H, CH2), 2.17, 2.05,
2.00, 1.94 (s, 12H, 4 ꢂ COCH3); 13C NMR (CDCl3, 125 MHz): d
175.9 (CH2CO); 170.5, 170.1, 169.8, 169.4 (COCH3); 83.8 (C-1);
76.6 (C-5); 71.3 (C-3); 68.4 (C-2); 65.6 (C-4); 62.5 (C-6); 28.6
(CH2); 20.7, 20.6, 20.4 (COCH3). Anal. Calcd for C18H23NO11S: C,
46.85; H, 4.99; N, 3.04; S, 6.94. Found: C, 47.42; H, 5.26; N, 3.03;
S, 6.63.
3.2.4. N-Phthalyl-S-(2,3,4,6-tetra-O-acetyl-a-D-
mannopyranosyl)sulfenamide (4b)
Starting from 0.5 g (1.37 mmol) of 1-thio-2,3,4,6-tetra-O-acetyl-
-D-mannopyranose (4a), the procedure described for 3a provided
a
0.32 g (45%) of 4b after purification by column chromatography
3.2.8. Benzyl-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)
disulfide (12)
(6:4 hexane/EtOAc). Syrup, ½a D25
ꢀ
ꢁ20.6 (c 0.50, CHCl3); 1H NMR
(CDCl3, 500 MHz): d 7.95 (dd, 2H, Aryl-H), 7.81 (dd, 2H, Aryl-H);
5.53 (dd, 1H, H-2, J1,2 1.3 Hz, J2,3 4.0 Hz); 5.51 (s, 1H, H-1); 5.34
(t, 1H, H-4, J3,4 10.1 Hz); 5.18 (dd, 1H, H-3); 4.81 (m, 1H, H-5);
4.28 (dd, H-6a, J6a,6b 12.7 Hz, J5,6a 4.7 Hz); 4.00 (dd, H-6b, J5,6b
3.1 Hz); 2.13, 2.07, 1.99, 1.98 (s, 12H, 4 ꢂ COCH3); 13C NMR (CDCl3,
125 MHz): d 170.4, 169.6, 169.5, 169.4 (COCH3); 167.2 (CO); 134.8,
131.8; 124.0 (Aryl-C), 85.53 (C-1); 70.4 (C-5); 69.6 (C-3); 67.2 (C-
2); 65.4 (C-4); 61.8 (C-6); 20.6, 20.5, 20.4 (COCH3). Anal. Calcd
for C22H23NO11S: C, 51.87; H, 4.52; N, 2.75; S, 6.29. Found: C,
51.89; H, 4.77; N, 2.80; S, 6.47.
To a stirred solution of 1b (150 mg, 0.294 mmol) in 10 mL
CH2Cl2 34 L (1 equiv, 0.294 mmol) toluenethiol was added, and
l
the mixture was stirred at room temperature. The reaction was
complete in 45 min (TLC, 6:4 hexane/EtOAc) and after evaporation,
the residue was purified by column chromatography (6:4 hexane/
EtOAc) to afford 12 as a white powder, 110 mg (75%), mp 117–
118 °C, lit.28 114–116 °C; ½a 2D5
ꢀ
ꢁ180.0 (c 2.0, CHCl3); lit.28 ꢁ185.0
(c 2.3, CHCl3); 1H NMR (CDCl3, 500 MHz): d 7.30–7.21 (m, Aryl-
H); (d, 1H, H-2); (d, 1H, H-3); (t, 1H, H-4, J3,4 9.6 Hz); 4.52 (d, 1H,
H-1, J1,2 9.8 Hz); 4.10 (s, CH2); 4.26 (dd, 1H, H-6a, J5,6a 4.9 Hz,
J6a,6b 12.5 Hz); 4.21 (dd, 1H, H-6b, J5,6a 2.0 Hz); 3.78 (m, 1H, H-5),
2.13, 2.10, 2.03, 2.00 (s, 12H, 4 ꢂ COCH3); 13C NMR (CDCl3,
125 MHz): d 170.19, 169.36, 169.08 (COCH3); 136.6, 128.6; 127.9,
127.5 (Aryl-C); 87.7 (C-1); 76.1 (C-5); 73.8 (C-3); 69.1 (C-2); 68.0
(C-4); 62.1 (C-6), 44.4 (CH2); 20.6, 20.6, 20.5 (COCH3). HRMS Calcd
for C21H26O9S2 [M+Na]+:509.10; Found: 508.91.
3.2.5. N-Succinyl-S-(2,3,4,6-tetra-O-acetyl-b-D-
glucopyranosyl)sulfenamide (1c)
To a stirred solution of 1a (0.5 g, 1.37 mmol in 5 mL EtOAc)
AgOAc (0.23 g, 1.37 mmol) was added. After 40 min (TLC indicated
consumption of the thiol) the mixture was cooled (0–4 °C) and
added to a cold (0–4 °C) solution of N-bromosuccinimide (0.24 g,
1.37 mmol in 5 mL EtOAc), stirred at rt for more than 10 min,
and filtered through Celite. Evaporation under reduced pressure
followed by column chromatography (1:1 hexane/EtOAc) afforded
3.2.9. Phenyl-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-
disulfide (13)
Method A: From 1b (150 mg, 0.294 mmol) and benzenethiol
1c as a white crystal, 0.42 g (65%), mp 197–199 °C; ½a D25
ꢀ
ꢁ35.7 (c
(30 lL, 0.294 mmol) as described for 12, colorless crystals,
0.51, CHCl3); 1H NMR (CDCl3, 500 MHz): d 5.20 (t, 1H, H-3, J2,3
100 mg (72%), mp 121–123 °C; lit.28 123–124 °C; ½a D25
ꢁ195.7 (c
ꢀ
3
9.8 Hz); 5.07 (t, 1H, H-2); 4.92 (t, 1H, H-4); 4.70 (d, 1H, H-1, J1,2
0.1, CHCl3); lit.28 ꢁ241 (c 1.9, CHCl3); 1H NMR (CDCl3, 500 MHz):
d 7.56–7.18 (m, 5H, Aryl-H); 5.25 (overlapping signals, 2H, H-2,
H-3); 5.10 (d, 1H, H-4); 4.62 (t, 1H, H-1); 4.15 (dd, 1H, H-6a);
4.09 (dd, 1H, H-6b); 3.74 (m, 1H, H-5), 2.12, 2.08, 2.02, 2.00 (s,
12H, 4 ꢂ OCOCH3); 13C NMR (CDCl3, 125 MHz): d 171.7, 168.6,
168.2 (COCH3); 148.2, 128.5, 128.3, 127.6, (Aryl-C); 87.6 (C-1);
75.8 (C-5); 73.4 (C-3); 68.9 (C-2); 67.8 (C-4); 64.6 (C-6), 20.5,
20.4, 20.4, 20.1 (COCH3). HRMS Calcd for C20H24O9S2 [M+Na]+:
495.53; Found: 495.17.
9.8 Hz); 4.20 (dd, 1H, H-6a, J6a,6b 12.3 Hz, J5,6a 5.1 Hz); 4.14 (dd,
1H, H-6b, J6a,6b 12.0 Hz, J5,6b 2.5 Hz) 3.67 (m, 1H, H-5); 2.86 (s,
4H, CH2), 2.11, 2.08, 2.04, 2,03 (s, 12H, 4 ꢂ COCH3); 13C NMR
(CDCl3, 125 MHz): d 176.3 (CH2CO); 170.5, 170.0, 169.8, 169.2
(COCH3); 86.2 (C-1); 76.1 (C-5); 73.8 (C-3); 68.9 (C-2); 67.3 (C-
4); 61.8 (C-6); 28.6 (CH2); 20.6, 20.5 (COCH3). Anal. Calcd for
C18H23NO11S: C, 46.85; H, 5.02; N, 3.04; S, 6.95. Found: C, 47.34;
H, 5.22; N, 3.02; S, 6.70. HRMS m/z Calcd for C18H23NO11
S
[M+Na]+: 484.0884. Found: 484.0862.
Method B: From 1c (100 mg, 0.325 mmol) and 33
lL
(0.325 mmol) benzenethiol as described for method A, 67 mg (61%).
3.2.6. N-Succinyl-S-(2,3,4,6-tetra-O-acetyl-b-D-
galactopyranosyl)sulfenamide (2c)
3.2.10. 2,3,4,6-Tetra-O-acetyl-b-
2,3,4,6-tetra-O-acetyl-b- -galactopyranoside (14)
Method A: To a solution of 1b (107 mg, 0.295 mmol) in 10 mL
CH2Cl2, 2a (150 mg, 0.295 mmol) was added. After stirring at room
D
-glucopyranosyl-(1,10)-dithio-
Compound 2c was prepared as described for 1c, starting from
0.50 g (1.37 mmol) of 2a. Syrup (after column chromatography,
D
1:1 hexane/EtOAc), 0.32 g (50%). ½a D25
ꢀ
ꢁ1.6 (c 0.5, CH2Cl2); 1H

1626
T.-Z. Illyés et al. / Carbohydrate Research 346 (2011) 1622–1627
temperature for 20 min, TLC (1:1 hexane/EtOAc) indicated disap-
pearance of the starting materials. The mixture was evaporated un-
der reduced pressure, and the residue was purified by
crystallization from EtOAc–hexane to give 14 as white crystals,
signals, 2H, Glc-H6a, Man-H5); 4.12–4.06 (overlapping signals, 2H,
Man-H6b, Glc-H6b); 3.23 (m, 1H, Glc-H5); 2.23–1.90 (s, 24H,
8 ꢂ COCH3); 13C NMR (C6D6, 125 MHz): d 170.5, 170.4, 170.1 (2ꢂ),
1
0
0
169.9, 169.7, 169.3, 169.2 (COCH3); 88.2 (Man-C1, JC1 –H1
196 mg (92%), mp 163–165 °C, lit.29 163–164 °C; ½a D25
ꢀ
+8.5 (c 1.5,
174.5 Hz); 88.1 (Glc-C1, JC1–H1 157.9 Hz); 76.7 (Glc-C5); 74.5
1
CHCl3); lit.29 +8.8 (c 1.8, CHCl3); 1H NMR (C6D6, 500 MHz): d 5.71
(Glc-C3); 72.3 (Man-C5); 70.3 (Man-C2); 69.9 (Man-C3); 69.8
(Glc-C2); 68.4 (Glc-C4); 66.4 (Man-C4); 62.5 (Man-C6); 61.6 (Glc-
C6); 20.7, 20.5, 20.4 (COCH3). Anal. Calcd for C28H38O18S2: C,
46.27; H, 5.23; S, 8.81. Found: C, 46.36; H, 5.19; S, 8.91.
0
0
(t, 1H, Gal-H2, J2 ,3 10.0 Hz); 5.60 (t, 1H, Gal-H4); 5.58 (t, 1H,
0
0
0
0
Glc-H2, J1,2 9.9 Hz); 5.38 (dd, 1H, Gal-H3, J2 ,3 9.9 Hz, J3 ,4 3.2 Hz);
5.37 (t, 1H, Glc-H4); 5.28 (t, 1H, Glc-H3, J3,4 9.9 Hz); 4.87 (d, 1H,
0
0
Gal-H1, J1 ,2 10.1 Hz); 4.34 (m, 1H, Glc-H6a); 4.26 (m, 1H, Gal-
H6a); 4.25 (d, 1H, Glc-H1, J1,210.1 Hz); 4.18 (m, 1H, Gal-H6b);
4.10 (m, 1H, Glc-H6b, J6a,6b 11.5, J5,6a 3.3 Hz); 3.88 (t, 1H, Gal-
H5); 3.34 (m, 1H, Glc-H5); 2.09, 2.06, 2.01, 1.97, 1.95 (s, 24H,
8 ꢂ COCH3); 13C NMR (C6D6, 125 MHz): d 170.6, 170.5, 170.2,
170.0, 169.6, 169.4, 169.1 (COCH3); 90.1 (Gal-C1); 87.0 (Glc-C1);
77.2 (Glc-C5); 75.4 (Gal-C5); 74.8 (Glc-C4); 72.7 (Gal-C3); 69.9
(Gal-C4); 68.5 (Gal-C2, Glc-C3); 68.0 (Glc-C2); 62.0 (Glc-C6); 61.7
(Gal-C6); 20.8, 20.7, 20.5, 20.4, 20.3 (COCH3). Anal. Calcd for
C28H38O18S2: C, 46.27; H, 5.23; S, 8.81. Found: C, 45.88; H, 5.16;
S, 8.74. HRMS m/z Calcd for C28H38O18S2 [M+H]+: 726.1578. Found:
726.1585.
3.2.13. 2,3,4,6-Tetra-O-acetyl-b-D
-glucopyranosyl-(1,10)-dithio-
2-deoxy-2-acetamido-3,4,6-tri-O-acetyl-b-D-glucopyranoside
(17)
Method A: 17 was prepared as described for 14 by reaction of
1-thio-2-deoxy-2-acetamido-3,4,6-tri-O-acetyl-b- -glucopyra-
D
nose32 (7, 107 mg, 0.295 mmol) with 1b (150 mg, 0.295 mmol).
Pale yellow crystals 190 mg (89%), mp 135–137 °C; ½a D25
ꢀ
+1.8 (c
4.00, CHCl3); 1H NMR (CDCl3, 500 MHz): d 6.06 (d, 1H, GlcNAc-
0
0
NH); 5.26 (t, 1H, GlcNAc-H3, J2 ,3 9.8 Hz); 5.22 (t, 1H, Glc-H3, J2,3
0
0
10.1 Hz); 5.12 (t, 1H, Glc-H2); 5.05 (t, 1H, GlcNAc-H4, J3 ,4
9.9 Hz); 5.01 (t, 1H, Glc-H4, J2,3 10.0 Hz); 4.73 (d, 1H, GlcNAc-H1,
0
0
MethodB: Reaction of 1c (120 mg 0.325 mmol) with 2a (150 mg,
0.325 mmol) under the above-mentioned conditions afforded 14,
240 mg (85%).
J1 ,2 9.9 Hz); 4.60 (d, 1H, Glc-H1, J1,2 10.4 Hz); 4.45 (dd, 1H, Glc-
0
0
0
0
H6a); 4.26 (dd, 1H, GlcNAc-H6a, J5 ,6a 2.5 Hz, J6a ,6b 12.5 Hz); 4.16
0
0
(dd, 1H, GlcNAc-H6b, J5 ,6a 4.3 Hz); 4.11 (dd, 1H, GlcNAc-H2);
4.06 (d, 1H, Glc-H6b, J5,6a 5.2 Hz); 3.79 (m, 1H, Glc-H5); 3.71 (m,
1H, GlcNAc-H5); 2.11, 2.09, 2.05, 1.99 (s, 24H, 8 ꢂ COCH3); 13C
NMR (CDCl3, 125 MHz): d 170.8, 170.7, 170.6, 170.1, 169.9, 169.3,
169.2, 169.1 (COCH3); 89.2 (GlcNAc-C1); 86.7 (Glc-C1); 76.2 (Glc-
NAc-C5); 76.0 (Glc-C5); 73.6 (Glc-C3); 73.4 (GlcNAc-C3); 69.6
(Glc-C2); 68.2 (GlcNAc-C4); 68.1 (Glc-C4); 61.9 (Glc-C6); 61.7 (Glc-
NAc-C6); 52.9 (GlcNAc-C2); 23.2, 20.8, 20.7, 20.6, 20.5, 20.4
(COCH3). Anal. Calcd for C28H39NO17S2: C, 46.34; H, 5.37; N, 1.93;
S, 8.82. Found: C, 46.09; H, 5.48; S, 9.00; N, 1.85; HRMS m/z Calcd
for C28H39O17S2N [M+H]+: 725.1738. Found: 725.1744.
3.2.11. 2,3,4,6-Tetra-O-acetyl-b-
2,3,4,6-tetra-O-acetyl-b- -mannopyranoside (15)
D
-glucopyranosyl-(1,10)-dithio-
D
Method A: 15 was prepared as described for 14 by reaction of 1b
(107 mg, 0.294 mmol) with 3a (150 mg, 0.295 mmol). Recrystalli-
zation from EtOAc/hexane afforded compound 15 as white crystals,
199 mg (93%), mp 186–188 °C, lit.3 187–188 °C; ½a D25
ꢁ118.0 (c
ꢀ
1.0), lit.3 ꢁ118.4 (c 1.26; CHCl3); 1H NMR (C6D6, 500 MHz): d
0
0
0
0
6.12 (d, 1H, Man-H2, J1 ,2 1.4 Hz); 5.72 (t, 1H, Man-H4, J3 ,4
9.8 Hz); 5.60 (dd, 1H, Glc-H2, J1,2 9.6 Hz); 5.52 (dd, 1H, Man-H3,
0
0
J2 ,3 1.4 Hz); 5.40 (m, 2H, Glc-H3, Glc-H4); 5.10 (s, 1H, Man-H1,
Method B: Reaction of 1c (120 mg 0.325 mmol) with 7 (150 mg,
0.325 mmol) under the above-mentioned conditions afforded 17,
194 mg (91%).
0
0
J1 ,2 1.5 Hz); 4.56 (dd, 1H, Glc-H6a, J5,6a 4.9 Hz, J6a,6b 12.5 Hz); 4.4
0
0
0
0
(dd, 1H, Man-H6a, J6a ,6b 11.7 Hz, J5 ,6a 3.3 Hz); 4.30 (dd, 1H, Glc-
0
0
H6b, J5,6b 2.2 Hz); 4.23 (dd, 1H, Man-H6b, J5 ,6b 1.5 Hz); 3.92 (d,
1H, Glc-H1); 3.65 (ddd, 1H, Man-H5); 3.39 (m, 1H, Glc-H5); 2.10,
2.07, 2.04, 1.96, 1.90 (s, 24H, 8 ꢂ COCH3); 13C NMR (C6D6,
3.2.14. 1,2:3,4-Di-O-isopropylidene-6-thio-(2,3,4,6-tetra-O-
acetyl-b-D-glucopyranosyl-thio)-a-D-galactopyranoside (18)
125 MHz):
d
170.5, 170.2, 170.0, 169.8, 169.6, 169.2, 169.0
To a stirred solution of 1b (250 mg, 0.49 mmol) in 25 mL CH2Cl2
1
1
0
0
(COCH3); 90.9 (Man-C1, JC1 –H1 155.7 Hz); 84.4 (Glc-C1, JC1–H1
160.2 Hz); 77.1 (Man-C5); 76.9 (Glc-C5); 73.7 (Glc-C3); 71.6
(Man-C3); 69.9 (Man-C2); 68.4 (Glc-C2); 68.1 (Glc-C4); 65.2
(Man-C4); 61.7 (Man-C6); 61.5 (Glc-C6); 20.6, 20.5, 20.3, 20.0,
19.7 (COCH3). Anal. Calcd for C28H38O18S2: C, 46.27; H, 5.23; S,
8.81. Found: C, 46.35; H, 4.92; S, 8.96. HRMS m/z Calcd for
was added 135 mg (0.49 mmol) 1,2:3,4-di-O-isopropylydene-6-
thio-a-D
-galactopyranoside33 (8) and stirred at room temperature
until TLC (1:1 hexane/EtOAc) indicated disappearance of starting
materials (ca. 4 h). After evaporation to dryness under reduced
pressure, the crude product was purified by column chromatogra-
phy (6:4 hexane/EtOAc) to give 18 as a yellowish syrup, 120 mg
C
28H38O18S2 [V+Y]+: 727.1578. Found: 727.1585.
(65%); ½a 2D5
ꢀ
+6.7 (c 0.33, CH2Cl2); 1H NMR (CDCl3, 500 MHz): 5.49
MethodB: Reaction of 1c (120 mg 0.325 mmol) with 3a (150 mg,
0.325 mmol) under the above-mentioned conditions afforded 15,
195 mg (91%).
(d, 1H, Gal-H1); 5.20 (t, 1H, Glc-H3); 5.12 (t, 1H, Glc-H2); 5.06 (t,
1H, Glc-H4); 4.62 (d, 1H, Glc-H1); 4.53 (dd, 1H, Gal-H3); 4.38
(dd, 1H, Gal-H2); 4.22 (dd, 1H, Gal-H4); 4.12 (dd, 1H, Glc-H6a),
4.10 (dd, 1H, Glc-H6b); 4.05 (m, 1H, Gal-H5); 3.72 (m, 1H, Glc-
H5); 3.05 (dd, 1H, Gal-H6a); 2.97 (dd, 1H, Gal-H6b); 2.12, 2.08,
2.02, 2.00 (s, 12H, 4 ꢂ OCOCH3); 1.51 (s, 3H, CH3); 1.37 (s, 3H,
CH3); 1.32 (s, 6H, CH3); 13C NMR (CDCl3, 125 MHz): d 170.7,
170.5, 169.3, 169.1 (COCH3); 109.2, 108.7 (Cqa); 96.5 (Gal-C1);
89.6 (Glc-C1); 75.9 (Glc-C5); 73.7 (Glc-C3); 71.6 (Gal-C2); 70.8
(Gal-C3); 70.4 (Gal-C4); 69.3 (Gal-C5); 68.1 (Glc-C2); 66.1 (Glc-
C4); 62.1 (Glc-C6), 39.4 (Gal-C6); 26.0, 25.8, 24.9, 24.3 (CH3);
20.54, 20.45 (COCH3). Anal. Calcd for C26H38O14S2: C, 48.90; H,
5.95; S, 10.03. Found: C, 48.87; H, 6.12; S, 9.40.
3.2.12. 2,3,4,6-Tetra-O-acetyl-b-
2,3,4,6-tetra-O-acetyl- -mannopyranoside (16)
To a stirred solution of 4b (50 mg, 0.098 mmol) in EtOAc (5 mL)
was added a solution of 1-thio-2,3,4,6-tetra-O-acetyl-b- -glucopyr-
D
-glucopyranosyl-(1,10)-dithio-
a-D
D
anose (1a, 36 mg, 0.098 mmol) in EtOAc (5 mL). The mixture was
stirred at room temperature with monitoring by TLC (4:6 Et2O/ben-
zene). After 2 h the mixture was evaporated to dryness, and the res-
idue purified by column chromatography (4:6 Et2O/benzene) to
afford 16 as a colorless oil, 63 mg (89%). ½a D25
ꢁ4.3 (c 0.11, CHCl3);
ꢀ
1H NMR (C6D6, 500 MHz): d 6.10 (dd, 1H, Man-H2); 5.70 (t, 1H,
0
0
0
0
Man-H4, J3 ,4 10 Hz); 5.65 (d, 1H, Man-H1, J1 ,2 < 1.0 Hz); 5.63 (dd,
3.2.15. Methyl-2,3-di-O-acetyl-4-thio-(2,3,4,6-tetra-O-acetyl-b-
0
0
1H, Man-H3, J2 ,3 3.1 Hz); 5.45 (t, 1H, Glc-H2, J1,2 9.5 Hz); 5.32 (t,
D
-glucopyranosyl-thio)-6-O-benzyl-
Methyl-2,3-di-O-acetyl-4-thio-6-O-benzyl-
side (9, 110 mg, 0.294 mmol)34,35 was dissolved in 10 mL CH2Cl2
a
-
D
-glucopyranoside (19)
0
0
1H, Glc-H3); 5.24 (t, 1H, Glc-H4); 4.36 (dd, Man-H6a, J6a ,6b
12.3 Hz, J5 ,6a 4.8 Hz); 4.23 (d, 1H, Glc-H1); 4.22–4.13 (overlapping
a-D
-glucopyrano-
0
0

T.-Z. Illyés et al. / Carbohydrate Research 346 (2011) 1622–1627
1627
and 150 mg (0.295 mmol) 1b was added. TLC (4:6 hexane/EtOAc)
indicated disappearance of the starting materials after stirring at
room temperature for 2 h. Evaporation under reduced pressure fol-
lowed by column chromatography (1:1 hexane/EtOAc) afforded 19
1H, Gln-CH ); 3.43 m, 1H, Cys-CH2a); 3.10 (dd, 1H, Cys-CH2b);
a
2.51 (m, 2H, Gln-CH2); 2.27, 2.28, 2.26, 2.21 (s, 12H, 4 ꢂ COCH3);
2.15, 2.04 (m, 2H, Gln-CH2b,b ); 13C NMR (DMSO, 125 MHz): d
0
170.9, 170.3, 170.0, 169.5, 169.3, 168.9 (COCH3); 86.1 (C-1); 74.4
(C-5); 72.8 (C-3); 68.7 (C-2); 67.8 (C-4); 61.8 (C-6); 52.9 (Gln-
CH); 51.8 (Cys-CH); 41.5 (Gly-CH2), 41.1 (Cys-CH2), 40.1 (Gln-
CH2), 39.9 (Gln-CH2); 26.6; 20.4, 20.3 (COCH3). Anal. Calcd for
as a colorless oil, 160 mg (72%); ½a D25
ꢀ
ꢁ29.2 (c 1.0, CH2Cl2); 1H NMR
(CDCl3, 500 MHz): d 7.56 (m, 4H, Aryl-H); 7.45 (m, 1H, Aryl-H);
5.91 (t, 1H, H-30); 5.40 (t, 1H, H-3, J2,3 10.2 Hz); 5.27 (t, 1H, H-
4);5.18 (t, 1H, H-2); 5.10 (d, 1H, H-10, J1 ,2 3.6 Hz); 4.90 (dd, 1H,
H-20, J2,3 9.8 Hz); 4.78 (dd, 2H, CH2Bn); 4.70–4.62 (overlapping sig-
nals, 2H, H-1, H-6a); 4.45–4.38 overlapping signals, 2H, H-5, H-6b);
C24H35N3O15S2: C, 43.04; H, 5.23; N, 6.27; S, 9.56. Found: C, 41.98;
0
0
H, 5.43; N, 6.25; S, 9.32. HRMS m/z Calcd for C24H35N3O15S2
[M+Na]+ 692.1402. Found: 692.1390.
4.18 (m, 1H, H50); 4.15 (dd, 1H, H-60a, J5 ,6 a 3.3 Hz); 3.91 (dd, 1H, H-
0
0
60b, J6 a,6 b 11.0 Hz, J5 ,6 b 1.5 Hz); 3.51 (s, 3H, OCH3); 3.19 (t, 1H, H-
40); 2.30, 2.24, 2.20, 2.15 (18H, 6 ꢂ COCH3); 13C NMR (CDCl3,
125 MHz): d 170.5, 170.1, 169.9, 169.3 (COCH3); 137.8, 128.4,
127.7 (Aryl-C); 96.8 (C-10); 89.5 (C-1); 75.8 (C-50); 74.0 (C-3);
73.7 (BnCH2); 72.5 (C-20); 69.8 (C-2); 69.6 (C-30); 68.6 (C-50); 68.3
(C-6); 67.3 (C-4); 61.4 (C-60); 55.1 (OCH3); 46.8 (C-40); 20.8, 20.6;
20.5, 20.4 (COCH3). Anal. Calcd for C32H42O16S2: C, 51.47; H, 5.63;
S, 8.58. Found: C, 50.78; H, 5.57; S, 8.35.
Acknowledgments
0
0
0
0
The skillful technical assistance of Sára Balla is greatly appreci-
ated. We thank the Hungarian Scientific Research Fund (OTKA NK-
68578), TÁMOP-4.2.2-08/1/2008-0019 and TÁMOP-4.2.1./B-09/1/
KONV-2010-0007 for financial support.
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12. Gamblin, D. P.; Garnier, P.; van Kasteren, S.; Oldham, N. J.; Fairbanks, A. J.;
Davis, B. G. Angew. Chem., Int. Ed. 2004, 43, 828–833.
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5309–5312.
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18. Behforouz, M.; Kerwood, J. E. J. Org. Chem. 1969, 34, 51–55.
3.2.16. S-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-thio)-
cysteine methylester (20)
L-Cysteine methyl ester hydrochloride (10, 50 mg, 0.294 mmol)
in dry MeOH (5 mL) was treated with 1 M sodium methoxide in
MeOH (0.29 mL, 0.294 mmol) at room temperature for 1 h. Amber-
list cation exchange resin was added for neutralization, the residue
was dissolved in 5 mL MeOH and 1b (150 mg, 0.294 mmol) in 5 mL
CH2Cl2 was added. After 2 h stirring at room temperature (2:3:0.2
hexane/EtOAc/MeOH), the reaction mixture was evaporated under
reduced pressure. Column chromatography (2:3:0.1 hexane/
EtOAc/MeOH) afforded 20 as pale yellowish solid, 120 mg (75%),
mp 101–102 °C, ½a D25
ꢀ
ꢁ177.2 (c 0.1, MeOH); 1H NMR (CD3OD,
500 MHz): d 5.34 (t, 1H, H-2, J2,3 10.0 Hz), 4.80 (t, 1H, H-1); 4.30
(dd, 1H, H-6a); 4.16 (dd, 1H, H-6b); 3.95 (m, 1H, H-5); 3.91 (m,
1H, CH); 3.78 (s, 1H, OCH3); 3.25 (dd, 1H, CH2); 2.91 (dd, 1H,
CH2); 2.06, 2.03, 2.01, 1.98 (s, 12H, 4 ꢂ COCH3); 13C NMR (CD3OD,
125 MHz): d 172.5, 171.7, 171.3, 170.9 (COCH3); 87.2 (C-1); 75.3
(C-5); 74.0 (C-3); 68.3.0 (C-2); 67.5 (C-4); 62.0 (C-6); 53.1 (Cys-
CH); 52.8 (OCH3); 43.1 (Cys-CH2); 21.03, 20.9, 20.7 (COCH3). Anal.
Calcd for C18H27NO11S2: C, 43.46; H, 5.43; N, 2.81; S, 12.87. Found:
C, 44.05; H, 5.83; S, 12.68; N, 2.75. HRMS m/z Calcd for
ˇ
ˇ
ˇ
ˇ
19. Cerny´, M.; Vrkoc, J.; Stanek, J. Collect. Czech. Chem. Commun. 1959, 24, 64–69.
ˇ
´
20. Cerny, M.; Stanek, J.; Pacák, J. Monatsh. Chem. 1963, 94, 290–294.
21. Matta, K. L.; Girotra, R. N.; Barlow, J. J. Carbohydr. Res. 1975, 43, 101–109.
22. Haque, M. B.; Roberts, B. P.; Tocher, D. A. J. Chem. Soc., Perkin Trans. 1 1998,
2881–2889.
C
18H27NO11S2 [M+H]+: 520.1026. Found: 520.0960.
23. Durette, P. L.; Shen, T. Y. Carbohydr. Res. 1980, 81, 261–274.
24. Perlin, A. S.; Casu, B. Tetrahedron Lett. 1969, 2921–2924.
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26. Hansen, P. E. Prog. Nucl. Magn. Reson. Spectrosc. 1981, 14, 249–251.
27. Szilágyi, L.; Györgydeák, Z. Carbohydr. Res. 1985, 143, 21–41.
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29. Brito, I.; Lopez-Rodriguez, M.; Bényei, A.; Szilágyi, L. Carbohydr. Res. 2006, 341,
2967–2972.
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1339–1343.
3.2.17. S-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-thio)-
glutathione (21)
Glutathione (11, 90 mg, 0.294 mmol) was dissolved in a mixture
of dioxane–water (20 mL, 1:1 v/v) and 150 mg (0.294 mmol) of 1b
added. The reaction mixture was stirred at room temperature with
monitoring by TLC (2:4:1.5 hexane/EtOAc/MeOH). After 2 h the
mixture was evaporated to dryness, and the residue was purified
by column chromatography (2:4:1 hexane/EtOAc/MeOH). To afford
21 as white powder, 160 mg (84%), mp 183–185 °C, ½a D25
ꢁ204.1 (c
ꢀ
0.32, water); 1H NMR (DMSO, 500 MHz): d 8.27, 8.71 s, 2Y, CO–NH);
5.61 (t, 1H, H-3, J2,3 8.0 Hz); 5.34 (t, 1H, J3,4 8.0 Hz, H-2); 5.78 (d, 1H,
34. Crich, D.; Li, H. M. J. Org. Chem. 2000, 65, 801–805.
35. Debenham, S. D.; Toone, E. J. Tetrahedron: Asymmetry 2000, 11, 385–387.
J1,2 10.1 Hz, H-1); 5.19 (t, 1H, H-4); 4.75 (m, 1H, Cys-CH ); 4.41–
a
4.28 (3H, H-5, H-6a, H-6b); 3.87–3.84 (m, 2H, Gly-CH2); 3.54 (m,