New phenyl 6,4'-substituted-1-thio-β-maltosides, building blocks for the synthesis of linear and branched malto-oligosaccharides

Article abstract of DOI:10.1055/s-2000-7601

An efficient strategy to synthesize a number of new phenylthio-maltoside derivatives in yields from 55 to 95% is described. These derivatives can be used as suitable building blocks for stepwise synthesis of starch derived malto-oligosaccharides.

Full text of DOI:10.1055/s-2000-7601

PAPER
1547
New Phenyl 6,4’-Substituted-1-Thio-b-Maltosides, Building Blocks for The
Synthesis of Linear and Branched Malto-oligosaccharides
Mohammed Saddik Motawia,*,a,c Kim Larsen,a,c Carl Erik Olsen,b,c Birger Lindberg Møllera,c
a Plant Biochemistry Laboratory, Department of Plant Biology, The Royal Veterinary and Agricultural University, 40 Thorvaldsensvej, DK-
1871 Frederiksberg C, Copenhagen, Denmark
b Department of Chemistry, The Royal Veterinary and Agricultural University, 40 Thorvaldsensvej, DK-1871 Frederiksberg C, Copenha-
gen, Denmark
c Center for Molecular Plant Physiology (PlaCe),The Royal Veterinary and Agricultural University, 40 Thorvaldsensvej, DK-1871 Frede-
riksberg C, Copenhagen, Denmark
Received 17 April 2000
compounds 2a and 3 are mandatory for the synthesis of
Abstract: An efficient strategy to synthesize a number of new phe-
the desired building blocks, and improved and fast access
to their synthesis in multi-gram-scale is required. Phase
nylthio-maltoside derivatives in yields from 55 to 95% is described.
These derivatives can be used as suitable building blocks for step-
transfer catalysis (PTC) has been extensively used in the
field of carbohydrate chemistry,11,12 in particular to
achieve nucleophilic substitutions at the anomeric center
of glycosyl halides using a wide variety of nucleophiles13
including aryloxides14,15 and arylthiolates.10,16 Therefore,
our strategy for improved and fast access to the maltose
derivatives 2a and 3 (Scheme 2) is based on phase transfer
catalysis (PTC). In a one-pot synthesis, b-maltose (1) was
converted into hepta-O-acetyl-a-maltosyl bromide using
acetic anhydride and hydrogen bromide in acetic acid,17
and subsequently treated with thiophenol under PTC con-
ditions using tetrabutylammonium hydrogen sulfate
(TBAHS) as catalyst10 to give 2a in 55% yield, after chro-
matographic purification. A second one-pot synthesis was
based on the same methodology, but using pentachlo-
rophenol as the nucleophile, and provided compound 3 in
57% yield, without chromatographic treatment. NMR
data and physical properties of both compounds 2a10 and
39b are consistent with the data previously reported.
wise synthesis of starch derived malto-oligosaccharides.
Key words: phenyl 1-thio-b-maltoside, benzylidenation, silylation,
benzylation, regioselective reductive cleavage
A practical and efficient strategy to achieve the chemical
synthesis of a large number of complex oligosaccharides
of interest for studies of starch biosynthesis and degrada-
tion requires a systematic approach based on a limited
number of building blocks. Thioglycosides have received
extensive attention due to their reactivity towards
thiophiles1 and their sensitivity to nucleophiles after con-
version into glycosyl halides2 thereby offering convenient
possibilities for subsequent manipulations at the anomeric
centre. Electrophilic3 and radical4 reactions have also
been reported. Various methods for the preparation and
use of these compounds have been reported.5 We have
previously reported a general method for removal of the
thiophenyl protecting group at the anomeric position to
generate a reducing sugar with the other original protect-
ing groups still present.6 On the other hand, the use of
thioglycosides offer distinct advantages due to their rela-
tive stability under chemical conditions typically used for
manipulation of other protective groups.2a Accordingly,
the phenylthio group was selected as the protecting group
for the anomeric center in the building blocks (Scheme 1).
Based on this strategy, we report efficient methodologies
including one-pot syntheses to obtain, in a multi-gram-
scale, a set of maltose-derived building blocks (Scheme 1)
that fulfil the requirements for efficient synthesis of com-
plex a-1Æ4- and a-1Æ6-malto-oligosaccharides. Mal-
tose was chosen as starting material because it is
commercially available, cheap, and because it already
contains an a-1Æ4- glycosidic bond thus saving one extra
coupling reaction.
The desired new building blocks 7a-c were synthesized
based on the use of cyclic acetal18 using 2a as the starting
material. Quantitative conversion of 2a into 2b was
achieved by deacetylation using sodium methoxide in
methanol. Reaction of 2b with a,a-dibromotoluene in
pyridine18c,d under reflux and subsequent in situ acetyla-
tion to facilitate work-up gave the 4',6'-O-benzylidene de-
rivative 4a in 65% yield without chromatographic
purification. The 1H NMR spectrum of 4a (Table 1, 2) re-
vealed a 1-proton-singlet signal at d = 5.47 ppm assign-
able to the methine proton of the benzylidene acetal
function. The 13C NMR spectrum (Table 3) showed the
corresponding methine carbon resonating at d = 101.5
ppm. Standard deacetylation of 4a by treatment with sodi-
um methoxide in methanol provided the related deacety-
lated product 4b (Scheme 2) in quantitative yield.
Benzylation of 4b using benzyl bromide-sodium hydride
in DMF afforded the corresponding benzylated product 4c
in 85% yield after purification by silica gel column chro-
matography. Reductive cleavage of the benzylidene acetal
function of 4c was performed regioselectively using sodi-
um cyanoborohydride-HCl (gas)-diethyl ether in THF,19
The per-O-acetylated phenyl 1-thio-b-maltoside 2a7,10 is
the key intermediate for the synthesis of building block 5.7
Likewise, the per-O-acetylated pentachlorophenyl 1-b-
maltoside 39b is the best suited precursor for the synthesis
of per-O-acetylated 1,6-anhydromaltose,9 which is impor-
tant for the synthesis of the building block 6.7,8 Thus both
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

1548
M. S. Motawia et al.
PAPER
OAc
O
AcO
AcO
OAc
OH
O
O
AcO
SPh
OAc
6
OBn
O
OH
OBn
O
BnO
BnO
HO
HO
RO
O
BnO
OBn
OH
OBn
OBn
OH
OBn
O
O
O
O
O
O
BnO
HO
BnO
SPh
SPh
OH
OBn
OH
OBn
1
R
5
7
OBn
O
a
b
c
H
acetyl
4-phenylbenzoyl
HO
BnO
O
OBn
R
O
O
O
BnO
SPh
OBn
R
10
a
b
c
bromoacetyl
chloroacetyl
4-phenylbenzoyl
Maltose-derived building blocks
Scheme 1
resulting in the desired building block 7a in 84% yield af- the free 6-OH group of 8c are its ability to survive during
ter chromatographic purification on silica gel. Acetylation reductive cleavage of the benzylidene acetal function of
of 7a with acetic anhydride in pyridine provided the cor- 8c concomitant with being readily removable under neu-
responding acetylated derivative 7b quantitatively. Reac- tral or basic conditions. Haloacetyl (bromo- or chloro-
tion of 7a with biphenylcarbonyl chloride in CH2Cl2 in acetyl)22 or 4-biphenylcarbonyl23 protecting groups were
presence of 4-(dimethylamino)-pyridine (DMAP) gave found to fulfil these criteria. Treatment of 8c with the ap-
the corresponding 4’-O-substituted phenylthio maltoside propriate carbonyl chloride in the presence of DMAP pro-
derivative 7c in 97% yield after chromatographic purifica- vided the desired products 9a-c in good yield (Scheme 3).
tion
Regioselective reductive cleavage of the benzylidene ace-
tal function of 9a-c was successfully achieved by using
the NaBH3CN-HCl (gas)-diethyl ether system in THF19 to
give the desired building blocks 10a-c in 63, 89 and 85%
yield, respectively, after chromatographic treatment.
The additionally required new maltose-derived building
blocks 10a-c were obtained by selective silylation of 4b
with tert-butyldiphenylsilyl chloride in DMF in the pres-
ence of imidazole,20 which provided the related 6-O-sily-
lated derivative 8a in 85% yield after chromatographic In conclusion, we have developed a multi-gram-scale
purification (Scheme 3). Attempted benzylation of com- practical strategy and an easy access to a number of build-
pound 8a using the DMF-NaH/benzyl bromide method ing blocks including, (1) building block 6 with a free OH
was unsatisfactory due to the instability of the silyl group group at the 6-position for use as a glycosyl acceptor
under these benzylation conditions. Instead, compound 8a needed for introduction of a-1Æ6-glycosyl linkages, (2)
was successfully benzylated under PTC conditions using building block 7 providing an access to the 4’-position of
TBAHS as catalyst10,21 to obtain 8b in 56% yield. The the non-reducing end for use as an acceptor suitable for in-
silyl group of 8b was removed by treatment with tetra-bu- troduction of a-1Æ4-glycosyl linkages, (3) building block
tylammonium fluoride in THF19 to give 8c quantitatively. 10 with a free 4’-position at the non-reducing end and si-
Important characteristics of a suitable protecting group for multaneously providing access to the 6-position to be used
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
New Phenyl 6,4’-Substituted-1-Thio-b-Maltosides
1549
1
4b
Ph
O
i, ii
i, iii
i, ii, iii
O
O
R2O
OR2
OR1
OAc
O
O
AcO
AcO
O
R2O
SPh
Cl
OR2
OAc
R1
tert-butyldiphenylsilyl
tert-butyldiphenylsilyl benzyl
R2
8
OAc
O
Cl
O
Cl
Cl
O
a
b
c
H
AcO
H
benzyl
OR
OAc
RO
RO
Cl
O
Ph
O
3
iv
O
OR
OR
2
R
ref. 9b
O
O
RO
O
O
O
R2O
R
a
Ac
H
R
b
OR2
SPh
9
OR
6
O
a
b
c
bromoacetyl
chloroacetyl
4-phenylbenzoyl
O
R2O
ref. 7
SPh
OR2
iv, v, vi
5
v
Ph
O
O
10a-c
O
OR
RO
R
Reagents and conditions: i) tert-butylchlorodiphenylsilane, DMF,
imidazole, 20 ∞C, 45 min, 85%; ii) TBAHS, benzyl bromide, 50% aq
NaOH, toluene, r.t., 3 days, 56%; iii) TBAF, THF, r.t., 1½ h, 95%;
iv) acid chloride, CH2Cl2, DMAP, -7 ∞C, 15 min, 88-96%;
v) NaBH3CN, THF, 4Å MS-activated powder, HCl-Et2O, 0 ∞C, 30
min, 63-89%
4
OR
O
a
b
c
Ac
H
Bn
O
RO
SPh
OR
Scheme 3
vii, viii, ix
which contain all major features of starch, i.e. the a-1Æ4
linkages and the a-1Æ6 branching point.
7a-c
Reagents and conditions: i) Ac2O, 33% HBr-AcOH, r.t., 2 h; ii)
TBAHS, thiophenol, 1M aq Na2CO3, r.t., 30 min, 55%; iii) TBAHS,
pentachlorophenol, 1M aq Na2CO3, r.t., 30 min, 57%; iv) a,a-dibro-
motoluene, pyridine, 140 ∞C, 2 h, Ac2O, r.t., overnight, 65%; v)
MeONa-MeOH, r.t., 1 h, 100%; vi) NaH, DMF, benzyl bromide, r.t.,
overnight, 85%; vii) NaBH3CN, THF, 4A MS-activated powder,
HCl-Et2O, 0 ∞C, 30 min, 84%; viii) Ac2O, pyridine, r.t., 6 h, quant.;
x) 4-phenylbenzoyl acid chloride, CH2Cl2, DMAP, -7 ∞C, 15 min,
97%
Mps were determined using a Mettler FP81 MBC Cell connected to
a Mettler FP80 Central processor unit. Optical rotations were mea-
sured at 21 ± 2 ∞C with an Optical Activity Ltd AA-1000 Polari-
meter. All reactions were monitored by TLC on aluminum sheets
coated with silica gel 60F254 (0.2 mm thickness, E. Merck, Darm-
stadt, Germany) and the components present were detected by char-
ring with 10% H2SO4 in MeOH. Column chromatography was car-
ried out using silica gel 60 (particle size 0.040-0.063 mm, 230-400
mesh ASTM, E. Merck). Solvent extracts were dried with anhyd
MgSO4 unless otherwise specified. Microanalysis was performed at
DB Lab-Danish Bioprotein A/S, Stenhuggervej 22, P.O. Box 829,
DK-5230 Odense M, Denmark. The 1H and 13C NMR spectra were
recorded on a Bruker Avance 400 spectrometer at 400 and 101
MHz, respectively. CDCl3 was used as solvent (unless otherwise in-
dicated), dH values are relative to internal TMS and dC values are
referenced to the solvent [dC (CDCl3) = 77.0; dC (CD3OD) = 49.5;
dC (Acetone-d6) = 206 ppm]. FAB spectra were recorded on a Joel
A505W mass spectrometer.
Scheme 2
for the introduction of an a-1Æ6-branch point in the a-
1Æ4-glucan chain. The thiophenyl group present at the
anomeric center of all selected building blocks can be eas-
ily removed to provide a free anomeric center, which may
be activated and used as a glycosyl donor at any stage of
the reaction sequences. The improved synthesis of both
compounds 2a and 3 constitutes a convenient and quick
route to building blocks 5 and 6. The availability of the
building blocks here reported has made it possible to ini-
tiate a program for the synthesis of oligosaccharides
Compounds 2a and 3 under Conditions of Phase Transfer
Catalysis using Bu4NHSO4 as Catalyst; General Procedure
A solution of 2,3,6,2',3',4',6'-hepta-O-acetyl-a-D-maltosyl bromide
[prepared in situ from b-maltose monohydrate (1, 40 g, 0.11 mol)
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

1550
M. S. Motawia et al.
PAPER
Table 1 1H NMR Data (CDCl3/TMS, dH in ppm) of Skeleton Protonsa for Compounds 4a–c, 7a–c, 8a–c, 9a–c and 10a–c
H
4a
4bb
4c
7a
7b
7c
8ac
1
4.71 d
4.79 t
5.29 t
4.94 dd
3.72 m
4.60 dd
4.24 dd
5.33 d
4.87 dd
5.44 t
3.62 t
4.56 d
3.21 dd
3.60 t
4.67 d
3.56 t
3.82 t
3.81 t
3.62 m
3.90 dd
4.15 m
5.67 d
3.50 dd
4.00 t
3.61 t
3.86 m
3.62 m
4.15 m
5.53 s
4.69 d
3.59 dd
3.82 t
4.70 d
3.57 dd
3.81 t
4.73 d
3.59 dd
3.85 t
4.80 d
2
3.39-3.48 m
3.73-3.88 m
3.73-3.88 m
3.61-3.69 m
4.05 dd
3
4
3.46 dd
3.36 td
3.64 m
3.81 m
5.13 d
3.49 dd
3.75 t
4.10 dd
3.60 m
3.81 dd
3.89 dd
5.63 d
3.44 dd
3.75 t
4.06 dd
3.61 td
3.83 dd
3.87 dd
5.58 d
3.51 dd
3.86 t
4.11 t
5
3.66 td
3.89 dd
3.95 dd
5.61 d
3.61 dd
4.06 t
6a
6b
1’
2’
3’
4’
5’
6’a
6’e
PhCH
4.08 dd
5.24 d
3.61-3.69 m
3.73-3.88 m
3.73-3.88 m
3.39-3.48 m
3.39-3.48 m
3.61-3.69 m
5.57 s
3.38 t
3.64 td
3.77 m
3.56 dd
3.49 dd
5.05 dd
3.87 m
3.36 dd
3.29 dd
5.36 dd
4.09 m
3.46 dd
3.38 dd
3.83 td
3.71 t
4.24 m
5.47 s
3.78 m
3.67 m
4.15 dd
4.48 s
H
8b
8c
9a
9b
9c
10a
10b
10c
1
4.74 d
4.74 d
3.52 dd
3.82 t
4.68 d
4.68 d
3.53 dd
3.78 t
4.72 d
3.55 dd
3.84 t
4.68 d
3.53 dd
3.79 t
4.68 d
4.73 d
3.58 dd
3.86 t
2
3.51-3.59 m
3.78 t
3.53 dd
3.78 t
3.53 dd
3.79 t
3
4
3.97-4.09 m
3.51-3.59 m
3.97-4.09 m
3.97-4.09 m
5.56 d
3.52 m
3.96 td
3.85 dd
4.01 m
5.63 d
3.53 dd
4.01 t
3.92 dd
3.78 m
4.36 dd
4.66 dd
5.45 d
3.51 dd
3.99 t
3.91 dd
3.77 m
4.37 dd
4.67 dd
5.45 d
3.51 dd
3.99 t
4.06 t
3.90 t
3.89 t
4.08 t
5
3.83 m
4.54 dd
4.90 dd
5.59 d
3.54 dd
4.05 t
3.66 m
4.38 dd
4.65 dd
5.44 d
3.45 dd
3.75 t
3.68 m
4.39 dd
4.66 dd
5.43 d
3.44 dd
3.72 t
3.78 m
4.52 dd
4.90 dd
5.63 d
3.48 dd
3.83 t
6a
6b
1’
2’
3’
4’
5’
6’a
6’e
PhCH
3.48 dd
3.91 t
3.51-3.59 m
3.75 m
3.62 t
3.61 t
3.61 t
3.61 t
3.59 td
3.66 m
3.66 m
3.72 m
3.59 td
3.68 m
3.68 m
3.68 m
3.67 td
3.78 m
3.52 dd
3.59 dd
3.86 m
3.70 t
3.68 m
3.70 t
3.68 m
3.70 t
3.61 m
3.88 t
3.97-4.09 m
3.51-3.59 m
5.56 s
4.33 dd
5.54 s
4.29 dd
5.53 s
4.28 dd
5.53 s
4.15 dd
5.49 s
a Chemical shifts for the protecting groups are given in the Experimental.
b Recorded in CD3OD.
c Recorded in acetone-d6
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
New Phenyl 6,4’-Substituted-1-Thio-b-Maltosides
1551
Table 2 First-order Coupling Constants [J (Hz)] for CDCl3 Solutions, unless otherwise stated
H
4a
9.8
4ba
9.7
4c
9.7
7a
9.7
7b
9.7
7c
9.7
8ab
9.8
1,2
2,3
9.0
8.7
9.0
9.0
9.2
8.9
9.2
8.9
9.0
9.5
1.9
4.0
11.1
3.6
9.7
9.7
9.7
2.5
3.8
10.2
8.6
8.8
8.8
8.8
nd
nd
nd
3,4
4,5
9.7
9.6
9.5
9.2
5,6a
5,6b
6a,6b
1’,2’
2’,3’
3’,4’
4’,5’
5’,6’a
5’,6’b
6’a,6’e
2.6
2.3
nd
2.3
2.3
2.3
4.7
4.6
3.6
4.3
4.3
3.8
11.5
3.8
nd
12.0
4.0
12.0
3.9
11.1
3.8
11.2
3.6
11.1
3.7
10.2
9.9
9.6
9.4
9.8
9.6
9.4
9.3
9.4
9.2
nd
9.6
9.4
9.3
10.1
3.1
10.1
2.8
nd
10.9
4.7
10.0
4.9
10.3
nd
nd
4.3
4.2
nd
10.9
10.0
10.3
10.7
10.7
nd
H
8b
8c
9.6
9a
9.7
9b
9.7
9c
9.7
10a
9.7
8.6
8.6
8.8
2.3
5.6
11.8
3.8
9.6
9.5
9.3
2.8
nd
10b
10c
1,2
10.1
8.8
8.8
nd
9.6
8.6
8.6
8.6
2.0
5.5
11.8
3.7
9.6
9.5
9.5
2.1
nd
9.7
8.5
8.5
8.5
2.3
5.2
12.0
4.0
9.7
9.5
9.4
2.5
2.4
3.7
10.9
2,3
8.7
8.7
8.8
8.5
8.8
2.3
4.8
11.8
3.8
9.4
9.4
nd
8.8
8.5
8.8
2.7
5.1
11.8
3.9
9.3
9.3
9.0
8.7
8.7
8.7
2.3
4.9
11.9
3.9
9.5
9.4
9.4
3,4
4,5
nd
5,6a
5,6b
6a,6b
1’,2’
2’,3’
3’,4’
4’,5’
4’,OH
5’,6’a
5’,6’e
6’a,6’e
nd
2.4
5.0
11.7
4.1
9.4
9.4
nd
nd
nd
3.8
9.6
9.4
nd
nd
nd
nd
10.0
4.7
10.0
4.3
10.1
4.1
10.0
4.6
nd
nd
10.0
10.0
10.0
10.0
nd
nd
a Recorded in CD3OD.
b Recorded in acetone-d6.
nd: Not analyzed due to overlapping signals.
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

1552
M. S. Motawia et al.
PAPER
Table 3 13C NMR Data (CDCl3/TMS; dC in ppm) of Skeleton Carbonsa for Compounds 4a–c, 7a–c, 8a–c, 9a–c and 10a–c
C
4a
84.9
4bb
89.3
4c
87.2
7a
7b
7c
8ac
88.4
1
87.2
80.9
86.7
72.5
78.7
69.1
96.9
78.9
81.2
71.3
70.6
69.6
87.3
80.8
86.5
73.6
78.8
97.1
79.1
79.1
79.1
70.6
69.5
68.7
87.3
80.9
86.4
74.4
78.8
69.5
97.3
79.1
79.0
71.2
69.8
68.8
2
70.7
76.5
72.5
63.5
62.5
96.5
70.8
68.5
78.8
76.1
68.4
101.5
73.4
79.3
81.1
80.5
62.5
103.4
74.8
72.1
82.5
65.0
69.8
103.0
80.9
86.8
71.8
78.4
73.4
97.6
78.8
78.6
82.3
63.3
68.9
101.1
82.2
79.8
71.7
74.8
63.9
103.5
81.9
78.9
73.1
64.6
69.3
102.2
3
4
5
6
1’
2’
3’
4’
5’
6’
PhCH
C
8b
8c
87.5
9a
87.2
9b
87.2
9c
87.1
10a
10b
10c
1
87.8
78.8
86.3
74.9
81.1
63.7
98.3
78.5
79.6
82.3
63.4
68.8
101.1
87.2
80.7
85.9
74.8
76.4
65.2
97.8
78.8
81.0
71.0
71.4
69.5
87.3
80.8
86.0
74.7
76.3
65.1
97.8
78.8
81.0
71.0
71.4
69.5
87.1
80.8
86.3
73.7
76.6
64.0
97.6
78.7
81.2
71.2
71.2
69.4
2
78.8
86.4
81.3
72.5
62.2
98.1
78.6
78.8
82.1
63.4
68.9
101.1
80.2
86.0
74.4
76.2
64.9
98.5
78.6
79.0
82.2
63.6
68.8
101.3
80.8
86.0
74.4
76.1
64.8
98.4
78.4
78.5
82.1
63.6
68.8
101.3
80.9
86.2
74.4
76.5
63.8
98.6
78.5
78.6
82.3
63.7
68.8
101.3
3
4
5
6
1’
2’
3’
4’
5’
6’
PhCH
a Chemical shifts for the protecting groups are given in the Experimental.
b Recorded in CD3OD.
c Recorded in acetone-d6.
by the method of Kartha and Jennings15] in EtOAc (500 mL) was
added gradually to a stirred mixture of Bu4NHSO4 (40 g, 0.12 mol),
thiophenol (34 mL, 0.33 mol) and/or pentachlorophenol (87.9 g,
0.33 mol), and 1 M aq Na2CO3 (800 mL) at r.t. The two-phase mix-
ture was vigorously stirred for 30 min at r.t. after which the organic
phase was separated, successively washed with 1 M aq NaOH
(3 ¥ 100 mL), H2O (3 ¥ 100 mL), brine (50 mL), and dried. The
solvent was evaporated in vacuo and the residue was chromato-
graphed and/or crystallized.
Phenyl 2,3,6-Tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-glu-
copyranosyl)-1-thio-b-D-glucopyranoside (2a)
The obtained residue was chromatographed on silica gel (300 g).
After an initial washing step with CH2Cl2 to remove all impurities,
the column was eluted with CH2Cl2/EtOAc (9:1) to give 2a as a
white amorphous material. Yield: 44 g (55%); mp 99-100 ∞C
[Lit.10, mp 93-95 ∞C]; [a]D +50.7 (c 1.31, CHCl3); [Lit.,10 [a]D
+47.4 (c 1.0, CHCl3)].
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
New Phenyl 6,4’-Substituted-1-Thio-b-Maltosides
1553
Pentachlorophenyl 2,3,6-Tri-O-acetyl-4-O-(2,3,4,6-tetra-O-
acetyl-a-D-glucopyranosyl)-b-D-glucopyranoside (3)
The obtained residue was crystallized twice from EtOH to give 3 as
a crystalline white solid. Yield: 54.9 g (57%); mp 170-171 ∞C
[Lit.,9b mp 171-172 ∞C]; [a]D +63.5 (c 1.41, CHCl3); [Lit.,9b [a]D
+63 (c 0.5, CHCl3)].
4.82, 4.90 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2), 7.12-7.61 (m, 35H, Ar-
H).
13C NMR (CDCl3): d = 73.9, 74.1, 75.2, 75.2, 75.2 (5 ¥ PhCH2),
126.0-138.6 (Ar-C).
MS (FAB): m/z = 995 [M+Na]+.
Anal. Calcd for C60H60O10S (973.20): C, 74.05; H, 6.21; S, 3.29.
Found: C, 73.92; H, 6.12; S, 3.15.
Phenyl 2,3,6-tri -O-acetyl-4-O-(2,3-di-O-acetyl-4,6-O-ben-
zylidene-a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside (4a)
A stirred solution of 2b3 (5 g, 11.51 mmol) and a,a-dibromotoluene
(2.5 mL, 15.1mmol) in dry pyridine (50 mL) was refluxed for 2 h at
140 ∞C, cooled to r.t. and Ac2O (30 mL) gradually added with stir-
ring for 24 h. The solvents were evaporated to dryness in vacuo and
the last traces of solvents were removed by repeated co-evaporation
with toluene (3 ¥ 50 mL). EtOH (50 mL) was added to the residue
and heated to dissolve oily impurities. After cooling to r.t., the re-
sulting precipitate was collected by filtration and crystallized from
EtOH to give 4a as crystalline solid.
Phenyl 4-O-(4,6-O-Benzylidene-a-D-glucopyranosyl)-6-O-tert-
butyldiphenylsilyl-1-thio-b-D-glucopyranoside (8a)
tert-Butylchlorodiphenylsilane (7.5 mL, 28.84 mmol) was added
dropwise to a stirred solution of 4b (4.2 g, 8 mmol) and imidazole
(4.2 g, 61.69 mmol) in dry DMF (100 mL) maintained at 0 ∞C using
an ice-bath. The ice-bath was removed and the mixture was stirred
for 45 min at 15-20 ∞C and diluted with EtOAc (400 mL) and H2O
(100 mL). The organic phase was separated and washed with sat.
NaHCO3 (3 ¥ 100 mL), H2O (3 ¥ 100 mL), brine (50 mL), and dried.
The solvent was evaporated in vacuo and the residue chromato-
graphed on silica gel (130 g) with 0-10% MeOH in CHCl3 to obtain
8a as a white amorphous material, crystalline from Et2O/n-pentane.
Yield: 4.2 g (65%); mp 196-197 ∞C; [a]D +29.6 (c 0.82, CHCl3).
1H NMR (CDCl3): d = 1.99, 2.04, 2.05, 2.06, 2.09 (5 ¥ s, 15H, 5 ¥
COCH3), 7.26-7.49 (m, 10H, Ar-H).
13C NMR (CDCl3): d = 20.5, 20.6, 20.6, 20.7, 20.9 (5 ¥ COCH3),
126.1-136.7 (Ar-C), 169.5, 169.6, 170.1, 170.1, 170.7 (5 ¥
COCH3).
Yield: 5.2 g (85%); mp 105-106 ∞C; [a]D +28.9 (c 0.73, CHCl3).
1H NMR (Acetone-d6): d = 1.06 (s, 9H, Si[C(CH3)3]), 4.52 (d, 1H,
J = 4.8 Hz, OH-2), 4.59 (d, 1H, J = 4.0 Hz, OH-3’), 5.23 (s, 1H, OH-
2’), 5.52 (s, 1H, OH-3), 7.22-7.50 (m, 20H, Ar-H).
13C NMR (Acetone-d6): d = 19.8 (Si[C(CH3)3]), 27.2 (Si[C(CH3)3),
127.3-139.1 (Ar-C).
Anal. Calcd for C35H40O15S (732.76): C, 57.37; H, 5.50; S, 4.38.
Found: C, 57.15; H, 5.58; S, 4.32.
Phenyl 4’,6’-O-benzylidene-1-thio-b-maltoside (4b)
Anal. Calcd for C41H48O10SSi (760.98): C, 64.71; H, 6.36; S, 4.21.
Found: C, 64.83; H, 6.26; S, 4.07.
MeONa (30%) in MeOH (10 mL) was added gradually to a stirred
suspension of 4a (10 g, 13.1 mmol) in dry MeOH (100 mL) at r.t.
Stirring was continued for 1 h at r.t. and the mixture neutralized by
addition of Dowex 50W-X8 (H+ form, 200-400 mesh, pre-washed
with EtOH) resin. The resin was filtered off and washed with MeOH
(4 ¥ 50 mL). The residue obtained upon evaporation of the com-
bined filtrates was co-evaporated with toluene (3 ¥ 50 mL). The
amorphous solid formed upon toluene treatment was collected by
filtration and air-dried to give chromatographically pure 4b (6.85 g,
100%) as a white amorphous material. An analytically pure sample
was obtained by flash chromatography on silica gel CH2Cl2/MeOH
(9:1); mp 95-97 ∞C; [a]D +43.2 (c 0.75, MeOH).
Phenyl 2,3-O-Benzyl-6-O-tert-butyldiphenylsilyl-4-O-(4,6-O-
benzylidene 2,3-di-O-benzyl -a-D-glucopyranosyl)-1-thio-b-D-
glucopyranoside (8b)
A solution of 8a (9 g, 11.83 mmol) in toluene (175 mL) was added
gradually to a stirred mixture of Bu4NHSO4 (6.54 g, 19.26 mmol),
benzyl bromide (65 mL), and 50% aq NaOH (105 mL) at r.t. Stir-
ring was continued for 3 days at r.t. after which the mixture was di-
luted with toluene (300 mL). The organic phase was separated and
washed with H2O (4 ¥ 100 mL), and dried. The solvent was evapo-
rated and the residue chromatographed on silica gel (210 g) with 0-
20% Et2O in n-pentane to obtain 8b (7.44 g, 56%) as a gum. An an-
alytical sample was obtained as a white powder from n-pentane; mp
54-56 ∞C; [a]D +4.3 (c 0.33, CHCl3).
1H NMR (CDCl3): d = 1.08 (s, 9H, Si[C(CH3)3]), 4.51, 4.66 (2 ¥ d,
2H, J = 12.0 Hz, PhCH2), 4.62, 4.87 (2 ¥ d, 2H, J = 10.0 Hz,
PhCH2), 4.69, 4.85 (2 ¥ d, 2H, J = 11.1 Hz, PhCH2), 4.82, 4.90 (2 ¥
d, 2H, J = 11.3 Hz, PhCH2), 7.16-7.77 (m, 40H, Ar-H).
1H NMR (CD3OD): d = 7.16-7.50 (m, 10H, Ar-H).
13C NMR (CD3OD): d = 127.6-139.1 (Ar-C).
Anal. Calcd for C25H30O10S (522.57): C, 57.46; H, 5.79; S, 6.14.
Found: C, 57.24; H, 5.93; S, 6.21.
Phenyl 2,3,6-Tri-O-benzyl-4-O-(2,3-di-O-benzyl-4,6-O-ben-
zylidene-a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside (4c)
A solution of 4b (3.52 g, 6.74 mmol) in dry DMF (50 mL) was
stirred with NaH (5.67 g, 60% in mineral oil) for 5 h at r.t. After
cooling to 0 ∞C, benzyl bromide (11 mL) was added dropwise to the
mixture and stirring was continued overnight at r.t. The mixture was
cooled to 0 ∞C and excess NaH was decomposed by dropwise addi-
tion of MeOH (50 mL). The solution was concentrated in vacuo and
diluted with EtOAc (200 mL) and H2O (100 mL). The organic phase
was separated, washed with H2O (4 ¥ 50 mL) and brine (25 mL),
and dried. The solvent was evaporated and the residue chromato-
graphed on silica gel (180 g) with 10-20% Et2O in n-pentane to
give 4c as a colourless syrup.
13C NMR (CDCl3): d = 19.4 (Si[C(CH3)3]), 27.0 (Si[C(CH3)3]),
73.6, 74.5, 75.1, 75.4 (4 ¥ PhCH2), 125.9-138.5 (Ar-C).
MS (FAB): m/z = 1143 [M+Na]+.
Anal. Calcd for C69H72O10SSi (1121.48): C, 73.90; H, 6.47; S, 2.86.
Found: C, 74.16; H, 6.67; S, 2.69.
Phenyl 2,3-di-O-Benzyl-4-O-(4,6-O-benzylidene-2,3-di-O-ben-
zyl-a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside (8c)
Tetrabutylammonium fluoride (1.1 M in THF, 20 mL) was added
dropwise to a stirred solution of 8b (10 g, 8.92 mmol) in THF (60
mL) at r.t. Stirring was continued for 1½ h at r.t. and the solvent was
removed in vacuo. The residue was dissolved in EtOAc (300 mL)
and H2O (100 mL) and the organic phase separated, washed with
H2O (3 ¥ 50 mL), sat. NaHCO3 (3 ¥ 50 mL), brine (50 mL), and
dried. The solvent was evaporated and the residue chromatographed
on silica gel (210 g) with 0-5% EtOAc in CH2Cl2 to give 8c (7.5 g,
95%) as a foam. An analytical sample was crystallized from Et2O/
Yield: 5.57 g (85%); [a]D +3.6 (c 0.42, CHCl3).
1H NMR (CDCl3): d = 4.52, 4.69 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2),
4.55, 4.83 (2 ¥ d, 2H, J = 10.3 Hz, PhCH2), 4.59, 4.68 (2 ¥ d, 2H,
J = 12.0 Hz, PhCH2), 4.73, 4.89 (2 ¥ d, 2H, J = 11.0 Hz, PhCH2),
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

1554
M. S. Motawia et al.
PAPER
Phenyl 2,3-Di-O-benzyl-4-O-(4,6-di-O-benzylidene-2,3-di-O-
benzyl-a-D-glucopyranosyl)-6-O-(4-phenylbenzoyl)-1-thio-b-D-
glucopyranoside (9c)
White powder; yield: 5.7 g (96%). An analytical sample was crys-
tallized from Et2O/n-pentane to give a white crystalline material;
mp 116-117 ∞C; [a]D +18.3 (c 0.68, CHCl3).
1H NMR (CDCl3): d = 4.50, 4.73 (2 ¥ d, J = 11.9 Hz, 2H, PhCH2),
4.59, 4.87 (2 ¥ d, J = 10.2 Hz, 2H, PhCH2), 4.74, 4.89 (2H, 2 ¥ d,
J = 11.5 Hz, PhCH2), 4.88 (s, 2H, PhCH2), 7.08-8.14 (m, 39H, Ar-
H).
n-pentane to obtain a white powder; mp 64-66 ∞C; [a]D +13.4 (c
0.31, CHCl3).
1H NMR (CDCl3): d = 4.50, 4.71 (2 ¥ d, 2H, J = 11.8 Hz, PhCH2),
4.59, 4.86 (2 ¥ d, 2H, J = 10.0 Hz, PhCH2), 4.73, 4.91 (2 ¥ d, 2H,
J = 11.6 Hz, PhCH2), 4.85, 4.89 (2 ¥ d, 2H, J = 11.9 Hz, PhCH2),
7.10-7.53 (m, 30H, Ar-H).
13C NMR (CDCl3): d = 74.0, 74.2, 75.2, 75.4 (4 ¥ PhCH2), 126.0-
138.4 (Ar-C).
MS (FAB): m/z = 905 [M+Na]+.
13C NMR (CDCl3): d = 74.1, 74.5, 75.1, 75.2 (4 ¥ PhCH2), 126.0-
145.8 (Ar-C), 165.8 (COPhPh).
Anal. Calcd for C53H54O10S (883.07): C, 72.09; H, 6.16; S, 3.63.
Found: C, 72.31; H, 6.32; S, 3.49.
MS (FAB): m/z = 1085 [M+Na]+.
6-O-Substituted Phenyl 1-Thio-b-maltosides (9a-c); General
Procedure
Anal. Calcd for C66H62O11S (1063.28): C, 74.55; H, 5.88; S, 3.02.
Found: C, 74.42; H, 5.66; S, 2.86.
A solution of the acid chloride (22.64 mmol) in dry CH2Cl2 (30 mL)
was added dropwise at -10 ∞C during a period of 10 min to a stirred
solution of 8c (5 g, 5.66 mmol) and DMAP (2.76 g, 22.64 mmol) in
dry CH2Cl2 (75 mL) under Ar. The mixture was stirred for an addi-
tional 15 min at -10 ∞C to -7∞C under Ar, after which solid
NaHCO3 (5 g) was added and diluted with EtOAc (200 mL). The
mixture was filtered through a sand pad on a silica gel layer and the
filtrate was washed successively with H2O (50 mL), 1 N aq HCl (3
¥ 25 mL), 1 N aq NaOH (4 ¥ 50 mL), H2O (4 ¥ 50 mL), and dried.
The solvent was evaporated in vacuo to dryness and the last traces
of solvents were removed by additional co-evaporation with toluene
(3 ¥ 50 mL). The resulting residue was purified by column chroma-
tography on silica gel (130 g) with 30-40% Et2O in n-pentane to
give the products 9a-c.
Building Blocks 7a and 10a-c via Regioselective Reductive
Cleavage of the Benzylidene Acetal Function of 4c and 9a-c;
General Procedure
A solution of 4c and/or 9a-c (5.14 mmol) and NaBH3CN (3.23 g,
51.4 mmol) in dry THF (100 mL) was stirred with 4Å molecular
sieves (3 g, activated powder) for 1 h at r.t.. After cooling to 0 ∞C, a
solution of HCl in Et2O was slowly added until the mixture became
acidic (pH region 2-3, gas evolution). Stirring was continued for 30
min at 0 ∞C and the mixture was diluted with EtOAc (100 mL) and
filtered through a Celite pad and a silica gel layer. The filtrate was
washed successively with H2O (3 ¥ 150 mL), sat. NaHCO3 (3 ¥ 100
mL), H2O (3 ¥ 100 mL), and brine (50 mL), and dried. The solvent
was evaporated in vacuo and the residue purified by column chro-
matography on silica gel (210 g) with 30-60% Et2O in n-pentane to
obtain 7a and/or 10a-c.
Phenyl 2,3-Di-O-benzyl-6-O-bromoacetyl-4-O-(4,6-di-O-ben-
zylidene-2,3-di-O-benzyl-a-D-glucopyranosyl)-1-thio-b-D-glu-
copyranoside (9a)
Colourless syrup; yield: 5 g (88%). An analytical sample was crys-
tallized from Et2O/n-pentane to obtain a white amorphous solid; mp
52-54 ∞C; [a]D +6.4 (c 0.49, CHCl3).
1H NMR (CDCl3): d = 3.83 (s, 2H, COCH2Br), 4.49, 4.69 (2 ¥ d,
2H, J = 12.0 Hz, PhCH2), 4.59, 4.86 (2 ¥ d, 2H, J = 10.0 Hz,
PhCH2), 4.74, 4.89 (2 ¥ d, 2H, J = 11.3 Hz, PhCH2), 4.85 (s, 2H,
PhCH2), 7.15-7.56 (m, 30H, Ar-H).
13C NMR (CDCl3): d = 25.6 (COCH2Br), 74.0, 74.4, 75.1, 75.3 (4 ¥
PhCH2), 125.9-138.4 (Ar-C), 166.6 (COCH2Br).
MS (FAB): m/z = 1027 [M+Na]+.
Phenyl 2,3,6-Tri-O-benzyl-4-O-(2,3,6-tri-O-benzyl-a-D-glu-
copyranosyl)-1-thio-b-D-glucopyranoside (7a)
Colourless syrup; yield: 4.21 g (84%); [a]D +13.0 (c 1.0, CHCl3).
1H NMR (CDCl3): d = 4.38, 4.48 (2 ¥ d, 2H, J = 12.2 Hz, PhCH2),
4.49, 4.5 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2), 4.56, 4.57 (2 ¥ d, 2H,
J = 12.1 Hz, PhCH2), 4.58, 4.84 (2 ¥ d, 2H, J = 10.5 Hz, PhCH2),
4.70, 4.86 (2 ¥ d, 2H, J = 11.3 Hz, PhCH2), 4.87, 4.92 (2 ¥ d, 2H,
J = 11.8 Hz, PhCH2), 7.12-7.62 (m, 35H, Ar-H).
13C NMR (CDCl3): d = 73.2, 73.2, 73.6, 74.2, 75.2, 75.3 (6 ¥
PhCH2), 126.5-138.7 (Ar-C).
MS (FAB): m/z = 997 [M+Na]+.
Anal. Calcd for C55H55BrO11S (1004.01): C, 65.80; H, 5.52; S, 3.19.
Found: C, 65.96; H, 5.73; S, 3.31.
Anal. Calcd for C60H62O10S (975.21): C, 73.90; H, 6.41; S, 3.29.
Found: C, 74.08; H, 6.55; S, 3.42.
Phenyl 2,3-Di-O-benzyl-6-O-chloroacetyl-4-O-(4,6-di-O-ben-
zylidene-2,3-di-O-benzyl-a-D-glucopyranosyl)-1-thio-b-D-glu-
copyranoside (9b)
Colourless syrup; yield: 4.9 g (90%). An analytical sample was
crystallized from Et2O/n-pentane to obtain a white amorphous sol-
id; mp 48-49 ∞C; [a]D +8.6 (c 0.77, CHCl3).
1H NMR (CDCl3): d = 4.05 (s, 2H, COCH2Cl), 4.49, 4.69 (2 ¥ d,
2H, J = 11.8 Hz, PhCH2), 4.59, 4.87 (2 ¥ d, 2H, J = 10.1 Hz,
PhCH2), 4.74, 4.89 (2 ¥ d, 2H, J = 11.4 Hz, PhCH2), 4.85 (s, 2H,
PhCH2), 7.14-7.56 (m, 30H, Ar-H).
Phenyl 2,3-Di-O-benzyl -6-O-bromoacetyl l-4-O-(2,3,6-tri-O-
benzyl-a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside (10a)
Colourless syrup; yield: 3.26 g (63%); [a]D +14.0 (c 0.88, CHCl3).
1H NMR (CDCl3): d = 2.44 (d, 1H, J = 2.8 Hz, OH-4'), 3.76 (s, 2H,
COCH2Br), 4.46, 4.57 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2), 4.53, 4.58
(2 ¥ d, 2H, J = 12.2 Hz, PhCH2), 4.61, 4.85 (2 ¥ d, 2H, J = 10.0 Hz,
PhCH2), 4.70, 4.87 (2 ¥ d, 2H, J = 11.4 Hz, PhCH2), 4.87, 4.92 (2 ¥
d, 2H, J = 11.7 Hz, PhCH2), 7.15-7.56 (m, 30H, Ar-H).
13C NMR (CDCl3): d = 25.7 (COCH2Br), 73.3, 73.6, 74.4, 75.2,
75.2 (5 ¥ PhCH2), 127.6-138.4 (Ar-C), 166.6 (COCH2Br).
MS (FAB): m/z = 1029 [M+Na]+.
13C NMR (CDCl3): d = 40.6 (COCH2Cl), 74.0, 74.4, 75.1, 75.3 (4 ¥
PhCH2), 125.9-138.3 (Ar-C), 166.7 (COCH2Cl).
MS (FAB): m/z = 981 [M+Na]+.
Anal. Calcd for C55H57BrO11S (1006.02): C, 65.67; H, 5.71; S, 3.19.
Found: C, 65.91; H, 5.95; S, 2.99.
Anal. Calcd for C55H55ClO11S (959.56): C, 68.84; H, 5.78; S, 3.34.
Found: C, 69.11; H, 5.93; S, 3.47.
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
New Phenyl 6,4’-Substituted-1-Thio-b-Maltosides
1555
Phenyl 2,3-Di-O-benzyl-6-O-chloroacetyl-4-O-(2,3,6-tri-O-ben-
zyl-a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside (10b)
Colourless syrup; yield: 4.40 g (89%); [a]D +15.6 (c 1.23, CHCl3).
1H NMR (CDCl3): d = 2.43 (d, 1H, J = 2.1 Hz, OH-4’), 3.97 (s, 2H,
COCH2Cl), 4.45, 4.58 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2), 4.53, 4.57
(2 ¥ d, 2H, J = 11.8 Hz, PhCH2), 4.61, 4.86 (2 ¥ d, 2H, J = 10.4 Hz,
PhCH2), 4.70, 4.87 (2 ¥ d, 2H, J = 11.2 Hz, PhCH2), 4.87, 4.91 (2 ¥
d, 2H, J = 12.0 Hz, PhCH2), 7.14-7.55 (m, 30H, Ar-H).
4.59, 4.73 (2 ¥ d, 2H, J = 11.5 Hz, PhCH2), 4.61, 4.85 (2 ¥ d, 2H,
J = 10.2 Hz, PhCH2), 4.90, 4.94 (2¥d, 2H, J = 11.7 Hz, PhCH2),
7.05-8.00 (m, 44 H, Ar-H).
13C NMR (CDCl3): d = 73.4, 73.5, 73.6, 74.0, 75.1, 75.2 (6 ¥
PhCH2), 126.5-145.8 (Ar-C), 165.0 (COPhPh).
MS (FAB): m/z = 1177 [M+Na]+.
Anal. Calcd for C73H70O11S (1155.42): C, 75.89; H, 6.11; S, 2.78.
Found: C, 76.03; H, 6.25; S, 2.65.
13C NMR (CDCl3): d = 40.7 (COCH2Cl), 73.4, 73.7, 74.4,75.3, 75.3
(5¥PhCH2), 127.7-138.4 (Ar-C), 166.8 (COCH2Cl).
MS (FAB): m/z = 983 [M+Na]+.
Acknowledgement
Anal. Calcd for C55H57ClO11S (961.57): C, 68.70; H, 5.98; S, 3.33.
Found: C, 68.92; H, 6.13; S, 3.17.
This work was financially supported by the EU FAIR programme
contract CT95-0568 and by the Danish National Research Founda-
tion.
Phenyl 2,3-Di-O-benzyl-6-O-(4-phenylbenzyol)-4-O-(2,3,6-tri-
O-benzyl-a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside
(10c)
References
Colourless syrup; yield: 4.60 g (85%). An analytical sample was
crystallized from Et2O/n-pentane as a white amorphous material;
mp 76-77∞C; [a]D +7.7 (c 0.74, CHCl3).
1H NMR(CDCl3): d = 2.53 (d, 1H, J = 2.5 Hz, 4’-OH), 4.35, 4.43 (2
¥ d, 2H, J = 12.4 Hz, PhCH2), 4.48, 4.63 (2 ¥ d, 2H, J = 11.6 Hz,
PhCH2), 4.60, 4.88 (2 ¥ d, 2H, J = 10.0 Hz, PhCH2), 4.75, 4.87 (2 ¥
d, 2H, J = 11.3 Hz, PhCH2), 4.91 (s, 2H, PhCH2), 7.08-8.15 (m,
39H, Ar-H).
(1) Weygand, F.; Ziemann, H.; Bestmann, H. J. Chem. Ber. 1958,
91, 2534.
Weygand, F.; Ziemann, H. Liebigs Ann. Chem. 1962, 657.
Wolfrom, M. L.; Groebke, W. J. Org. Chem. 1963, 28, 2986.
Koto, S.; Uchida, T.; Zen, S. Bull. Chem. Soc. Jpn. 1973, 46,
2520.
Lemieux, R. U.; Hendriks, K. B.; Stick, R. V.; James, K. J.
Am. Chem. Soc. 1975, 97, 4056.
Paulsen, H. Angew. Chem., Int. Ed. Engl. 1982, 21, 155.
Nicolaou, K. C.; Dolle, R. E.; Papahatjis, D. P.; Randall, J. L.
J. Am. Chem. Soc. 1984, 106, 4189.
Leontein, K.; Nilsson, M.; Norberg, T. Carbohydr. Res. 1985,
144, 231.
13C NMR (CDCl3): d = 73.4, 73.5, 74.3, 75.2, 75.3 (5 ¥ PhCH2),
127.0-145.8 (Ar-C), 165.8 (COPhPh).
MS (FAB): m/z = 1087 [M+Na]+.
Anal. Calcd for C66H64O11S (1065.87): C, 74.37; H, 6.05; S, 3.01.
Found: C, 74.52; H, 6.22; S, 2.82.
Norberg, T.; Ritzen, H. Glycoconjugate J. 1986, 3, 135.
(2) Reviews: a) Fügedi, P.; Garegg, P. J.; Lönn, H.; Norberg, T.
Glycoconjugate J. 1987, 4, 97; and references cited therein.
b) Michalska, M.; Michalski, J. Heterocycles 1989, 28, 1249.
(3) Crich, D.; Ritchie, T. J. J. Chem. Soc., Chem. Commun. 1988,
985.
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Lett. 1984, 24, 1867.
(5) Horton, D.; Hutson, D. H. Adv. Carbohydr. Chem. 1963, 18,
123.
Phenyl 2,3,6-Tri-O-benzyl-4-O-(4-O-acetyl-2,3,6-tri-O-benzyl-
a-D-glucopyranosyl)-1-thio-b-D-glucopyranoside (7b)
Ac2O (5 mL) was added to a stirred solution of 7a (5 g, 5.13 mmol)
in dry pyridine (100 mL) and stirring was continued for 6 h at r.t.,
after which the solvents were evaporated in vacuo and the last traces
of solvents removed by co-evaporation with toluene (3 ¥ 50 mL).
The residue was dissolved in EtOAc (150 mL), H2O (50 mL), and
the organic phase was separated, washed with sat. NaHCO3 (4 ¥ 50
mL), H2O (3 ¥ 50 mL), and brine (25 mL), and dried. Evaporation
of the solvent to dryness afforded chromatographically pure 7b as a
colourless syrup; yield: 5.2 g (quant.); [a]D +24.8 (c 0.40, CHCl3).
1H NMR (CDCl3): d = 1.81 (s, 3H, COCH3), 4.34, 4.46 (2 ¥ d, 2H,
J = 12.0 Hz, PhCH2), 4.45, 4.57 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2),
4.54 (s, 2H, PhCH2), 4.56, 4.76 (2 ¥ d, 2H, J = 11.5 Hz, PhCH2),
4.59, 4.84 (2 ¥ d, 2H, J = 10.2 Hz, PhCH2), 4.88 (s, 2H, PhCH2),
7.11-7.60 (m, 35H, Ar-H).
Norberg, T. In Modern Methods in Carbohydrate Synthesis;
Khan, S. H.; O’Neill, R. A., Eds.; Harwood Academic
Publishers: Amsterdam, 1996; p 82; and references cited
therein.
Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997, 52, 179;
and references cited therein.
(6) Motawia, M. S.; Marcussen, J.; Møller, B. L. J. Carbohydr.
Chem. 1995, 14, 1279.
(7) Motawia, M. S.; Olsen, C. E.; Møller, B. L.; Marcussen, J.
Carbohydr. Res. 1994, 252, 69.
(8) Sakairi, N.; Hayashida, M.; Amano, A.; Kuzuhara, H. J.
Chem. Soc., Perkin Trans 1 1990, 1301.
(9) a) Asp, L.; Lindberg, B. Acta Chem. Scand. 1952, 6, 941.
b) Fujimaki, I.; Ichikawa, Y.; Kuzuhara, H. Carbohydr. Res.
1982, 101, 148.
13C NMR (CDCl3): d = 20.8 (COCH3), 73.3, 73.4, 73.5, 74.3, 75.0,
75.2 (6 ¥ PhCH2), 126.5-138.5 (Ar-C), 169.5 (COCH3).
MS (FAB): m/z = 1039 [M+Na]+.
Anal. Calcd for C62H64O11S (1017.25): C, 73.21; H, 6.34; S, 3.15.
Found: C, 73.45; H, 6.60; S, 3.37.
c) Bock, K.; Pedersen, H. Acta Chem. Scand., Ser. B 1988, 42,
75.
(10) Tropper, F. D.; Andersson, F. O.; Grand-Maître, C.; Roy, R.
Synthesis 1991, 734.
Phenyl 2,3,6-Tri-O-benzyl-4-O-[4-O-(4-phenylbenzoyl)-2,3,6-
tri-O-benzyl-a-D-glucopyranosyl]-1-thio-b-D-glucopyranoside
(7c)
(11) Roy, R. In Handbook of Phase Transfer Catalysis; Sasson, Y.;
Neumann, R., Eds.; Chapman & Hall: Hampshire, 1997;
p 244.
(12) Roy, R.; Tropper, F. D.; Cao, S.; Kim, J. M. ACS Symp. Series
1997, 659, 163.
Compound 7a was converted into compound 7c as described above
for compounds 9a-c and purified by column chromatography on sil-
ica gel with 20% EtOAc in n-pentane to give 7c as a colourless syr-
up; yield: (97%); [a]D -12.3 (c 0.83, CHCl3).
1H NMR (CDCl3): d = 4.35, 4.44 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2),
4.49, 4.58 (2 ¥ d, 2H, J = 12.0 Hz, PhCH2), 4.56 (s, 2H, PhCH2),
Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York

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M. S. Motawia et al.
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Article Identifier:
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Synthesis 2000, No. 11, 1547–1556 ISSN 0039-7881 © Thieme Stuttgart · New York