Synthesis of new sulfonic acid-containing oligosaccharide mimetics of sialyl Lewis A

Article abstract of DOI:10.1016/j.tet.2010.01.100

Two trisaccharides as new sulfonic acid mimetics of the sialyl Lewis A tetrasaccharide were synthesized. The natural sialic acid residue is replaced by a C-sulfonic acid moiety attached to position C-3′ of the lactosamine unit of the mimetics. The l-fucos

Full text of DOI:10.1016/j.tet.2010.01.100

Tetrahedron 66 (2010) 2404–2414
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of new sulfonic acid-containing oligosaccharide mimetics
of sialyl Lewis A
a
a
a,
a
a,b
*
´
´
´
´
´
´
Zsolt Jakab , Aniko Fekete , Aniko Borbas , Andras Liptak , Sandor Antus
a Research Group for Carbohydrates of the Hungarian Academy of Sciences, University of Debrecen, H-4010 Debrecen, PO Box 94, Hungary
b Department of Organic Chemistry, University of Debrecen, H-4010 Debrecen, PO Box 20, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 August 2009
Received in revised form 14 December 2009
Accepted 27 January 2010
Available online 2 February 2010
Two trisaccharides as new sulfonic acid mimetics of the sialyl Lewis A tetrasaccharide were synthesized.
The natural sialic acid residue is replaced by a C-sulfonic acid moiety attached to position C-30 of the
lactosamine unit of the mimetics. The L-fucose unit was also replaced by a D-arabinose ring in one of the
analogues. Formation of the sulfonic acid moiety on the trisaccharide level could be successfully achieved
by means of introduction of an acetylthio moiety into the galactose skeleton and subsequent oxidation.
The equatorial arrangement of the acetylthio group linked to C-3 of the galactose ring could be achieved
by double nucleophilic substitution; efficient formation of the gulo-triflate derivatives required
low-power microwave activation. Oxidation of the acetylthio group was carried out using Oxone in acetic
acid.
Dedicated to Professor Ka´roly Lempert on
the occasion of his 85th birthday
Keywords:
Selectins
Ó 2010 Elsevier Ltd. All rights reserved.
Sialyl Lewis A
Double nucleophilic displacement
Sugar sulfonic acid
1. Introduction
To prevent the above-mentioned pathological processes, de-
velopment of various sLea and sLex mimetics, which can inhibit the
Selectins are members of the family of adhesive molecules. This
name comes from their selective property and collective lectin
domain.1,2 Three different calcium ion-dependent carbohydrate-
binding proteins were identified: L-selectin is expressed on neu-
trophils, monocytes and lymphocyte subsets of leucocytes,
whereas, E-selectin and P-selectin are expressed on endothelial
cells and on thrombocytes (platelets).3,4 These proteins are
responsible for the initial steps of extravasation of leucocytes
during an inflammatory response and cancer metastasis by the
recognition of their specific carbohydrate ligands. Asthma, psoria-
sis, rheumatoid arthritis, ARDS, lupus, cancer metastasis, septic
shock or reperfusion syndrome diseases are all based on
lymphocyta-endothel connection.5
binding events of selectins with their natural ligands would be an
effective tool.
HO
OH
HO
O
OH
O
OH
OH
OH
HOOC
O
O
H3C
HO
O
HO
HO
AcHN
O
O
OH
NHAc
O
OH
OH
OH
HO
OH
O
HOOC
O
OH
O
O
O
H3C
OH
HO
HO
AcHN
O
OH
NHAc
OH
OH
HO
1
2
Figure 1. Sialyl Lea (1) and sialyl Lex (2).
Sialyl Lewis A tetrasaccharide 1 (sLea) and its positional isomer
sialyl Lewis X tetrasaccharide 2 (sLex) are the natural ligands of
selectins (Fig. 1). They are expressed on cell surfaces. Sialyl Lea is
related to the Lewis blood group system, while sLex was originally
described as the X-hapten, which was later designated Lex. These
carbohydrate epitopes have been identified as lead compounds for
binding to P- and E-selectins and also bind to L-selectin.6–8
On the other hand, sLea and sLex are tumour markers, since they
are highly expressed on many malignant cells, and they have been
demonstrated to be a prognostic indicator of metastatic diseases.
The CA19-9 antibody, used in one of the top cancer diagnostic
assays, binds sLea and indicates the presence of this antigen in
pancreatic and gastrointestinal cancer patient’s sera.9
A mixture of sulfated Lea and Lex was isolated by Yuen et al.10
These natural oligosaccharides were even more potent inhibitors
than the sialylated Lewis antigens.11 The present paper describes
the synthesis of the new sLea mimetics 3 and 4, in which the sialic
* Corresponding author. Tel./fax: þ36 52512900/22342.
´
E-mail address: borbasa@puma.unideb.hu (A. Borbas).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.100

Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
2405
acid unit is replaced by a sulfonic acid group (Fig. 2). This group has
a stronger ionic character and we expect higher stability against
Therefore, compound 924 was prepared as starting material for
the synthesis of donor 5. Inversion of the configuration at C-30 via
formation of a triflate and subsequent displacement with tetrabu-
tylammonium nitrite (TBANO2) afforded the gulo-derivative 10 in
good yield. Formation of the C-3 triflate derivative of 10 and
treatment with potassium thioacetate (KSAc) gave the desired
3-acetylthio-galactosyl derivative 11 in two steps with a 87% overall
yield. Oxidation of the SAc moiety was achieved with Oxone25 to
give the sulfonic acid sodium salt 12 in a yield of 68%. Then com-
pound 12 was converted to the donor molecule 5: debenzylation
and debenzylidenation of 12 and subsequent acetylation afforded
sulfatases and esterases. The
L-fucosyl unit was also replaced by
a
D
-arabinosyl moiety in compound 4 because such a structure is
more stable towards enzymatic degradation12 than the highly acid
sensitive
a
-L
-fucosyl interglycosidic linkage.13
HO
OH
OH
O
R
OH
OH
HO
NaO3S
O
O
O
OMe
NHAc
O
the triacetyl derivative 13, as a mixture of a/b anomers, in 60% yield.
OH
To transform the sulfonic acid salt group of 13 into an ester (14),
first, the sulfonic acid was liberated by Amberlite IR-120 cationic
exchange resin, and then methylation with diazo-methane in
ether afforded compound 14 in a moderate yield, also as a mixture
3 R=H
4 R=CH3
Figure 2. New synthetic analogues of the sLea.
of
a promoter and thioethanol as a reagent gave the anomeric mixture
15 only in a moderate yield. The -bromide derivative 5 was freshly
a/b anomers. Thioglycoside formation of 14 using BF3$OEt2 as
2. Results and discussion
a
prepared using bromine immediately before the coupling reaction
(Scheme 1).
For the preparation of the planned oligosaccharide sulfonic
acids, introduction of the easily oxidizable thioacetyl group into the
Ph
Ph
Ph
O
O
O
O
O
O
AcO
R1
OAc
O
AcO
MeO3S
OAc
O
b
a
d
g
O
O
O
OBn
OBn
OBn
HO
R
BzO
BzO
BzO
BzO
BzO
R
HO
10
Br
11 R=SAc
13 R=OAc, R1=SO3Na
14 R=OAc, R1=SO3Me
15 R=SEt, R1=SO3Me
5
9
c
e
f
12 R=SO3Na
Scheme 1. Reagents and conditions: (a) Tf2O, pyridine, dry CH2Cl2, ꢀ20 ꢁC to rt, 1 h, then TBANO2, dry CH3CN, rt, one day, 78%; (b) Tf2O, pyridine, dry CH2Cl2, ꢀ30 ꢁC to 0 ꢁC, 1 h,
then KSAc, dry DMF, one day, 87%; (c) Oxone, KOAc, glacial acetic acid, two days, rt, 68%; (d) Pd(C), H2, four days, then Ac2O, pyridine, rt, 60%; (e) Amberlite IR-120Hþ, MeOH, then
CH2N2, dry Et2O, 0 ꢁC, 1 h, 44%; (f) BF3$OEt2, dry CH2Cl2, HSEt, 0 ꢁC, 1 h, 48%; (g) Br2, dry CH2Cl2.
carbohydrate skeleton seemed to be the best approach.14–17 The
synthesis of the target molecules may be accomplished by two
synthetic paths; introduction of the thioacetyl group either at the
monosaccharide or at oligosaccharide level.
Surprisingly, coupling of acceptor 8 with the methylsulfonic acid
group-containing galactosyl bromide 5 under Helferich conditions
afforded exclusively the disaccharide 1726,27 in 40% yield
(Scheme 2) whose interglycosidic linkage was assigned to be
a on
the basis of the NMR data (for C-10: 105.49 ppm, JC1 –H1 ¼179 Hz).
0
0
Our plan was to prepare a sulfonic acid ester-containing
monosaccharide through formation of a thioacetyl function by
nucleophilic substitution, followed by oxidation and subsequent
conversion of the sulfonic acid salt into the appropriate methyl
ester. Then the synthesis of the trisaccharides 3 and 4 were planned
using the monosaccharide precursors 5–8 as depicted in Figure 3.
Some unusual a-galactosylations have been known in the litera-
ture.28,29 The methylsulfonic acid group may decrease the
p-donor
ability of the carbonyl oxygen of the benzoyl group by a strong
dipole–dipole interaction, therefore the glycosylium ion cannot be
stabilized in form of an acyloxonium cation intermediate despite
the possibility of neighbouring group participation.
D
-Arabinopyranosyl bromide 6 and L
-fucosyl bromide 718 were used
as the donors, and allyl N-acetyl-glucosamine 819 was selected as
the acceptor in the glycosylation reactions. The anomeric allyl
group was chosen because of its capability of conjugation to
proteins.20 It is known from the literature21–23 that 3-acetylthio-
galactoside can be prepared via two subsequent nucleophilic
substitution reactions, and a strict substitution pattern of the
galactose is required for the successful synthesis: OH-2 has to be
protected by an ester group, and OH-4 and OH-6 have to be
protected in the form of a benzylidene acetal.23
Ac
O
O
Ac
O
Ph
O
O
O
+
O
MeO3S
HO
BzO
NHAc
Br
5
8
a
OAc
O
AcO
MeO3S
Ph
O
O
BzO
O
O
O
AcHN
16
AcO
MeO3S
BnO
R
OAc
O
Scheme 2. Reagents and conditions: (a) Hg(CN)2, dry CH3NO2, dry toluene, rt,11/2 h, 40%.
OBn
O
Ph
O
O
OBn
Br
O
O
HO
BzO
NHAc
Br
To eliminate this problem we changed our synthetic strategy
and tried to create the sulfonic acid moiety at the oligosaccharide
level, therefore the known disaccharide 17 was used for the prep-
aration of the desired trisaccharides. The glucosamine acceptor was
6 R=H
5
8
7
R=CH3
Figure 3. The anticipated sugar building blocks.

2406
Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
also changed to the N-phthaloylated thioglucoside.18 According to
our expectation the phthaloyl group ensured better solubility and
higher yields. The ethylthio aglycone was expected to make the
synthesis of higher oligosaccharides possible for further synthetic
studies. The reductive ring opening method30 of the known
Before introduction and oxidation of the acetylthio moiety the
ethylthio aglycon, which is also oxidizable, had to be changed into
a non-oxidizable function. Therefore compounds 27 and 29 were
converted into the appropriate methyl glycosides with dry MeOH in
the presence of the NIS-TMSOTf promoter system to afford 30 and
32 in high yields. Dechloroacetylation of 30 with thiourea35 gave
the C-30 hydroxyl derivative 31 in 73% yield (Scheme 6).
b
-linked disaccharide 1731,32 was used for the formation of the
6-O-benzyl derivative 18. Treatment of 18 with the donors 6 and 7
by means of the in situ anomerization procedure18 furnished the
trisaccharide derivatives 20 and 21 in 52% and 56% yields,
respectively (Scheme 3).
BnO
R
BnO
R
OBn
OBn
OBn
OBn
O
O
Ph
Ph
BnO
a
O
O
OBn
BnO
R
O
O
OBn
OBn
Br
OBn
O
OBn
O
O
R
6
OBn
O
O
O
O
O
OR2
O
R1O
R1O
R=H
O
SEt
OMe
O
AcO
OAc
O R1O
OBn
O
7 R=CH3
OBz
NPhth
OBz
NPhth
AcO
AcO
OAc
O
SEt
O
O
AcO
b
SEt
NPhth
O
1
1
OAc
27
R=H, R =CA
29 R=CH3, R1=H
30
R=H, R =CA
NPhth
b
OAc
1
31
R=R =H
17 R1=R2=PhCH<
19
a
32 R=CH3, R1=H
R=H
1
2
20 R=CH3
18
R =H, R =Bn
Scheme 6. Reagents and conditions: (a) NIS, TMSOTf, dry MeOH, CH2Cl2, ꢀ70 ꢁC to rt,
overnight, 85% for 30, 84% for 32; (b) thiourea, pyridine, CH2Cl2, MeOH, overnight, 73%.
Scheme 3. Reagents and conditions: (a) BF3$OEt2, Et3SiH, dry CH2Cl2, 0 ꢁC, 3 h, 77%;
(b) TBABr, dry DMF, rt, one day, 52% for 19, 56% for 20.
To avoid cleavage of the phthalimido ring, deacetylation of
compounds 19 and 20 was carried out carefully in dry THF and
MeOH in the presence of 1–2 drops of 30% NaOMe in MeOH to
afford 21 and 22 in good yields. The hydroxyl groups at C-4 and C-6
of the galactose units of 21 and 22 were protected in form of
benzylidene acetals, then dibutylstannylidene-mediated acylation
with chloroacetyl chloride33,34 was applied to selectively protect
the position C-30 of 23 and 24 to give 25 and 26 in 70% and 79%
yields (Scheme 4).
Formation of the C-30 triflate derivatives of 31 and 32 and sub-
sequent treatment with TBANO2 afforded the gulo-compounds 33
and 34 in good yields. The critical step was the formation of the
gulo-triflates, which was carried out using Tf2O in pyridine in the
presence of a catalytic amount of DMAP. TLC monitoring of this
reaction showed only 40% conversion of the starting material at rt
after three days. We assume that there might be a strong hydrogen
bonding between the OH-30group and the C-20 benzoyl carbonyl
oxygen, and the phthalimido group may cause sterical hindrance as
well, giving rise to the low reactivity of this hydroxyl group. To
reach complete formation of the gulo-triflate, low-power activation
microwave (CEM Discover Microwave machine) was employed.
After 1 h TLC indicated >90% conversion of the starting com-
pounds. Treatment of the triflates with KSAc afforded the desired,
fully protected C-30 thioacetylated Lea mimetics 35 and 36 in 70%
and 78% overall yields for the two steps (Scheme 7).
OBn
OBn
BnO
OBn
OBn
O
R
O
Ph
OBn
O
R
c
R3O
OBn
O
OR4
O
OBn
O
O
O
O
R2O
O
SEt
O
O
SEt
CAO
OR1
NPhth
OH
25 R=H
NPhth
19 R=H, R1=R2=R3=R4=Ac
20 R=CH3, R1=R2=R3=R4=Ac
a
b
26 R=CH3
1
2
3
4
a
21
R=H, R =R =R =R =H
1
2
3
4
22
BnO
R
BnO
R
R=CH3, R =R =R =R =H
23 R=H, R1=R2=H, R3=R4=PhCH
24 R=CH3, R1=R2=H, R3=R4=PhCH
OBn
O
OBn
b
OBn
OBn
O
Ph
Ph
O
O
a
O
O
OBn
O
OBn
O
Scheme 4. Reagents and conditions: (a) 1–2 drops of 30% NaOMe in MeOH, dry
THF–MeOH (1:1), rt, 1 h, 90% for 21, 88% for 22; (b) PhCH(OMe)2, cat. CSA, dry CH3CN,
rt, 4 h, 82% for 23, 78% for 24; (c) Bu2SnO, dry toluene, then ClAcCl, dry DMF, toluene,
4 Å MS, 0 ꢁC, 1 h, 70% for 25, 79% for 26.
O
O
O
O
OMe
OMe
O
R1
O
HO
OBz
OBz
NPhth
NPhth
R2
33 R=R1=H, R2=OH
34 R=CH3, R1=H, R2=OH
31 R=H
32
Benzoylation of the hydroxyl group of 25 could be achieved by
using BzCl in pyridine and 1 equiv of 4-dimethylaminopyridine
(DMAP) to afford 27 in 80% yield. In the case of the fucosylated
derivative 26 under similar condition only 44% yield of compound
28 was formed since the longer reaction times resulted also in the
dechloroacetyl derivative 29 (34%) (Scheme 5).
R=CH3
b
2
1
b
35
R=R =H, R =SAc
36 R=CH3, R1=SAc, R2=H
Scheme 7. Reagents and conditions: (a) Tf2O, pyridine, dry CH2Cl2, ꢀ20 ꢁC to rt, 1 h,
then TBANO2, dry CH3CN, rt, one day, 70% for 33, 67% for 34; (b) Tf2O, pyridine, dry
CH2Cl2, 0 ꢁC, 1/2 h, then MW, 35 ꢁC, 1 h, then KSAc, dry DMF, overnight, 70% for 35, 78%
for 36.
BnO
R
BnO
R
Oxidation of the arabinose-containing thioacetyl derivative 35
with Oxone gave 37 in 56% yield. Salt 37 was then treated with
ethylenediamine (EDA) in ethanol at reflux to remove the acyl
protecting groups followed by N-acetylation with Ac2O in MeOH36
to develop the acetamido group of 38 (64%). To achieve higher
yields in the case of the fucose-containing trisaccharide 36 the
opposite sequence of the reactions was applied. First, compound 36
was deacylated with EDA followed by selective acetylation of the
amino group with Ac2O in MeOH, then the liberated thiol was
oxidized with Oxone to afford 39 with 62% overall yield for the
three steps (Scheme 8).
OBn
OBn
OBn
OBn
O
O
Ph
Ph
O
O
a
O
O
OBn
O
OBn
O
O
O
O
OR1
O
R2O
SEt
SEt
O
O
CAO
OH
NPhth
NPhth
25 R=H
26 R=CH3
27 R=H, R1=Bz, R2=CA
28 R=CH3, R1=Bz, R2=CA
29 R=CH3, R1=Bz, R2=H
Scheme 5. Reagents and conditions: (a) BzCl, dry CH2Cl2, pyridine, DMAP, rt, 2–4 h,
from 25: 80% for 27, from 26: 44% for 28, 34% for 29.

Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
2407
BnO
R
BnO
R
performed under anhydrous conditions (using argon) and moni-
tored by TLC on Kieselgel 60 F254 (Merck) visualized under UV light
and charred with 5% sulfuric acid in ethanol. Column chromatog-
raphy was performed on Silica Gel 60 (Merck 0.062–0.200 nm).
Chemicals were purchased from Aldrich and Fluka and used
without further purification. Molecular sieves were activated by
heating to 360 ꢁC overnight and were cooled over P2O5 in vacuo.
The organic solutions were dried over MgSO4, and concentrated in
vacuum. The 1H (200.13, 360.13, 400.13 and 500.13 MHz) and 13C
NMR (50.3, 90.54, 100.62 and 125.76 MHz) spectra were recorded
with Bruker WP-200SY, Bruker AM-360, Bruker DRX-400 and
Bruker DRX-500 spectrometers for solutions in CDCl3. The use of
a different solvent is indicated therein. The 1H–13C HSQC and 1H–1H
COSY experiments were performed on Bruker DRX-400 and Bruker
DRX-500 spectrometers at 298 K. Chemical shifts are referenced to
Me4Si (0.00 ppm for 1H) or to the residual solvent signals
(77.00 ppm for 13C). IR spectra were recorded on a Perkin–Elmer 16
PC FTIR spectrometer. Microwave-assisted procedures were taken
place in a CEM-Discover Focused Microwave Synthesis System
(2450 MHz) with a built-in infrared temperature sensor and
a CEM-Explorer computer controlled robotic sampler attaching
system. Samples were measured in 10 mL crimp-sealed, thick-
walled reaction tubes equipped with a magnetic stirrer. MALDI-TOF
MS spectra were recorded on a Bruker Biflex III spectrometer in the
positive, linear mode using satd 2,4,6-trihydroxyacetophenone in
water as matrix.
OBn
OBn
OBn
OBn
O
O
Ph
Ph
O
O
a
c
O
O
OBn
O
OBn
O
R1
O
O
OR2
O
O
R3
O
OMe
OMe
O
AcS
OBz
NPhth
37 R=H, R1=NPhth, R2=Bz, R3=SO3Na
38 R=R2=H, R1=NHAc, R3=SO3Na
35 R=H
b
36 R=CH3
1
2
3
39
R=CH3, R =NHAc, R =H, R =SO3Na
Scheme 8. Reagents and conditions: (a) from 35, Oxone, glacial AcOH, KOAc, rt, two
days, 56% for 37; (b) EDA, dry EtOH, reflux, one day, then Ac2O, MeOH, rt, 2 h, 64% for
38; (c) from 36, EDA, dry EtOH, reflux, one day, then Ac2O, MeOH, then Oxone, cc.
AcOH, KOAc, rt, 4 h, 62% for 39 over three steps.
The benzyl ethers and the benzylidene acetal of 38 were re-
moved in two steps. Acid hydrolysis and hydrogenolysis in the
presence of Pd/C catalyst gave the target compound 3 in high yield.
In the case of 39, removal of these protecting groups was achieved
only by hydrogenolysis to furnish compound 4 as the second new
sulfonic acid trisaccharide mimetic of the sLea tetrasaccharide 1
(Scheme 9).
BnO
HO
R
OBn
O
OH
OBn
R
OH
O
Ph
O
O
a
b
OMe
OBn
O
HO OH
OH
O
O
O
O
O
4.2. General method I for the synthesis of the benzylidene
acetal derivatives
O
O
OMe
NHAc
NaO3S
NaO3S
OH
NHAc
OH
38 R=H
3 R=H
39 R=CH3
4 R=CH3
To a solution of the starting material (15.5 mmol) in dry
acetonitrile (80 mL) was added benzaldehyde dimethylacetal
Scheme 9. Reagents and conditions: (a) from 38, 80% AcOH, 50 ꢁC, 1 h, then Pd(C), H2
(10 bar), EtOH, one day, 93% for 3; (b) from 39, Pd(C), H2 (10 bar), 96% EtOH, four days,
92% for 4.
(3.5 mL, 1.5 equiv) and
a
catalytic amount of (ꢂ)10-cam-
phorsulfonic acid (CSA) (90 mg) and the mixture was stirred at rt
until the complete conversion of the starting material (detected
by TLC). The mixture was neutralized with triethylamine (TEA)
and the solvent was evaporated. The crude product was purified
by crystallization or by column chromatography using 1% of TEA
in the eluent.
3. Conclusion
In conclusion, two trisaccharides (3, 4) as new sulfonic acid
analogues of the sialyl Lewis A were synthesized. These compounds
contain a sulfonic acid sodium salt moiety attached equatorially to
C-3 of the galactose ring substituting the natural sialic acid residue.
The trisaccharides were synthesized from monosaccharide building
4.3. General method II for the reductive ring opening of the
benzylidene acetal derivatives with BF3$OEt2/Et3SiH
blocks, the natural L D-arabinose
-fucose unit of sLea was replaced by
in mimetic 3. Formation of the sulfonic acid function was carried
out, first, on the monosaccharide level by means of introduction of
an acetylthio moiety to position C-3 and subsequent oxidation,
To a cold (0 ꢁC) solution of the starting material (0.34 mmol) in
dry CH2Cl2 was added Et3SiH (272 mL, 5 equiv) and BF3$OEt2 (86 mL,
2 equiv). The mixture was allowed to reach rt and was stirred for
4 h, then it was diluted with CH2Cl2, washed with satd aq NaHCO3,
washed again with water, dried (MgSO4) and concentrated. The
crude product was purified by column chromatography.
however the desired
b-galactosylation attempted with the
3-sodiumsulfonato-galactosyl donor failed. Introduction of the
sulfonic acid moiety on the trisaccharide level proved to be
the successful method. The equatorial arrangement of the
acetylthio group linked to C-3 of the galactose ring could be ach-
ieved by double nucleophilic substitution; while synthesis of the
galacto-triflates took place smoothly, for the efficient formation of
the gulo-triflate derivatives low-power microwave activation was
required. Oxone in the presence of acetic acid was used as the
reagent for the oxidation of the masked thiol group.
4.4. General method III for the in situ anomerisation
reactions with TBABr
The appropriate bromide donor was freshly prepared from the
corresponding ethyl 1-thioglycoside derivative (1.1 equiv) in dry
CH2Cl2 (3 mL) by adding Br2 (193 mL, 1.1 equiv) at rt. After half an
hour the mixture was concentrated under reduced pressure and
coevaporated twice with dry toluene. To a mixture of the acceptor
(1 equiv) and 3 Å MS in dry DMF was added TBABr (1.2 equiv) and
stirred for 2 h at rt, then the solution of the bromide derivative in
CH2Cl2 was added. After one day the mixture was diluted with
CH2Cl2 and filtered through Celite. The filtrate was washed twice
with water, dried (MgSO4) and concentrated. The crude product
was purified by column chromatography.
4. Experimental section
4.1. General
Optical rotations were measured at rt with a Perkin–Elmer 241
automatic polarimeter. Melting points were determined on a Kofler
hot-stage apparatus and are uncorrected. All reactions were

2408
Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
4.5. General method IV for the preparation of the
gulo-configured derivatives
4.8. Benzyl 2-O-benzoyl-4,6-O-benzylidene-3-deoxy-3-
sodiumsulfonato- -galactopyranoside (12)
b-D
To a solution of the starting compound (1.2 mmol) in dry
CH2Cl2 (5 mL) and pyridine (1 mL) was added dropwise Tf2O
(1.9 mmol, 1.6 equiv) at ꢀ30 ꢁC and the mixture was stirred for
1 h. After dilution with CH2Cl2, it was washed with satd aq
NaHCO3, and with water, dried (MgSO4) and concentrated.
The crude triflate was dried under high vacuum for 3 h. To
a solution of the crude triflate in dry acetonitrile (10 mL) was
added TBANO2 (3 equiv) and stirred overnight. When TLC
indicated the complete conversion of the triflate the mixture
was concentrated. The residue was diluted with EtOAc, washed
three times with water, dried (MgSO4) and concentrated. The
crude product was purified by column chromatography.
To a suspension of compound 11 (1.37 g, 2.6 mmol) in glacial
acetic acid (50 mL) was added KOAc (5.15 g, 20 equiv) and Oxone
(4.02 g, 2.5 equiv) and the reaction stirred vigorously for two days.
TLC analysis indicated the completion of the reaction. The reaction
mixture was neutralized by adding satd aq and solid NaHCO3 and
washed three times with EtOAc. The collected organic phase was
washed with water, dried (MgSO4) and concentrated. Column
chromatography (95:5/9:1 CH2Cl2–MeOH, Rf 0.46) of the residue
gave compound 12 (0.926 g, 68%) as a syrup and 11 (0.158 g, 12%)
23
was also recovered. Compound 12: [
NMR (360 MHz, CD3OD)
a
]
D
ꢀ25.8 (c 0.10, CHCl3). 1H
d
¼8.04 (dd, 2H, J¼8.3, 1.2 Hz, arom.),
7.65–7.55 (m, 3H, arom.), 7.45 (t, 2H, J¼7.7 Hz, arom.), 7.38–7.28 (m,
3H, arom.), 7.18–7.03 (m, 5H, arom.), 5.87 (dd, 1H, J¼11.3, 7.9 Hz,
H-2), 5.69 (s, 1H, PhCH), 4.86 (d, 1H, J¼12.6 Hz, PhCH2), 4.79 (d, 1H,
J¼7.9 Hz, H-1), 4.67 (d, 1H, J¼2.5 Hz, H-4), 4.63 (d, 1H, J¼12.4 Hz,
PhCH2), 4.27 (dq, 2H, J¼12.5,1.5 Hz, H-6a,b), 3.71–3.68 (m,1H, H-5),
3.51 (dd, 1H, J¼11.4, 2.9 Hz, H-3) ppm. 13C NMR (90 MHz, CD3OD)
4.6. Benzyl 2-O-benzoyl-4,6-O-benzylidene-b-D-
gulopyranoside (10)
Prepared from 9 (548 mg, 1.2 mmol) according to general
method IV and purified by column chromatography (1:1 EtOAc–
hexane, Rf 0.49) to give compound 10 (411 mg, 75%) as a col-
d
¼167.20 (PhC]O), 137.17, 136.67, 133.27, 130.01, 129.37, 128.79,
128.10, 127.93, 127.61, 125.98 (arom. Cs), 100.83, 100.06 (PhCH or
C-1), 74.11, 68.70, 68.46 (C-2, C-4, C-5), 70.27 (PhCH2), 68.96 (C-6),
61.21 (C-3) ppm. Anal. Calcd for C27H25NaO9S (548.54): C, 59.12; H,
4.59; Na, 4.19; S, 5.85. Found: C, 59.02; H, 4.62; S, 5.89. MALDI-TOF:
m/z calcd for [MþNa]þ 571.101. Found: 570.792.
23
ourless syrup: [
d
a
]
ꢀ57.9 (c 0.13, CHCl3). 1H NMR (360 MHz)
D
¼7.96 (dd, 2H, J¼8.3 Hz, J¼1.2 Hz, arom.), 7.55–7.45 (m, 3H,
arom.), 7.42–7.10 (m, 10H, arom.), 5.48 (s, 1H, PhCH), 5.38 (dd,
1H, J¼8.4, 3.1 Hz, H-2), 5.10 (d, 1H, J¼8.4 Hz, H-1), 4.89 (d, 1H,
J¼12.7 Hz, PhCH2), 4.65 (d, 1H, J¼12.7 Hz, PhCH2), 4.34–4.25 (m,
2H), 4.02–3.95 (m, 2H), 3.8–3.7 (m, 1H), 2.93 (br s, 1H, OH) ppm
4.9. 1,4,6-Tri-O-acetyl-2-O-benzoyl-3-deoxy-3-
sodiumsulfonato-a,b-D-galactopyranose (13)
13C NMR (90 MHz)
d
¼165.3 (PhC]O), 137.7, 137.66, 133.34,
129.91, 129.81, 129.14, 128.73, 128.47, 128.31, 127.73, 127.61,
126.48 (arom. C), 101.18 (PhCH), 96.85 (C-1), 76.4, 71.34, 71.2,
68.92, 65.66 (skeleton Cs), 70.15 (PhCH2), 69.31 (C-6) ppm. Anal.
Calcd for C27H26O7 (462.49): C, 70.12; H, 5.67. Found: C, 70.01;
H, 5.78.
To a solution of compound 12 in ethanol (5 mL) and acetic acid
(96%, 1 mL) was added 10% Pd/C (50 mg) and the reaction stirred
under H2 overnight. The mixture was diluted with ethanol and
filtered through Celite. The filtrate was concentrated under
diminished pressure. The residue was treated with Ac2O (0.75 mL)
and pyridine (1 mL) for 2 h. Then the mixture was concentrated and
coevaporated twice with toluene. Column chromatography (9:1
CH2Cl2–MeOH) of the residue gave an unseparable mixture of the
4.7. Benzyl 3-S-acetyl-2-O-benzoyl-4,6-O-benzylidene-b-D-
galactopyranoside (11)
a
and b anomers of 13 in a 4:1 ratio (109 mg, 57%) as a syrup. Anal.
To a solution of compound 10 (1.64 g, mmol) in dry CH2Cl2
(30 mL) and pyridine (2 mL) was added dropwise Tf2O (955 L,
Calcd for C19H21NaO12S (496.42): C, 45.97; H, 4.26; S, 6.46. Found: C,
45.89; H, 4.29; S, 6.50. MALDI-TOF: m/z calcd for [MþNa]þ 519.055.
Found: 519.204.
m
3.55 mmol, 1.6 equiv) at ꢀ50 ꢁC and the mixture was allowed to
reach 0 ꢁC and stirred for 1 h. The mixture was diluted with CH2Cl2,
washed with satd aq NaHCO3, washed again with water, dried
(MgSO4) and concentrated. The crude triflate was dried under high
vacuum for 3 h. To a solution of the crude triflate in dry DMF
(15 mL) was added KSAc (1.21 g, 10.6 mmol, 3 equiv) and the
reaction stirred overnight at rt. The residue was diluted with
CH2Cl2, washed three times with water, dried (MgSO4) and con-
centrated. Column chromatography (1:1 EtOAc–hexane) of the
4.10. 1,4,6-Tri-O-acetyl-2-O-benzoyl-3-deoxy-3-
methylsulfonato-a,b-D-galactopyranose (14)
To a solution of compound 13 (0.896 g, 1.8 mmol) in MeOH
(5 mL) was added Amberlite IR-120Hþ cation exchange resin until
pHw1. The mixture was filtered and cooled to 0 ꢁC and freshly
prepared diazo-methane in ether was added until a pale yellow
colour was sustained. The mixture was concentrated under
diminished pressure and was purified by column chromatography
(98:2 CH2Cl2–acetone, Rf 0.50) to give an unseparable mixture of
residue gave compound 11 (1.64 g, 87%) as a syrup. Crystallization
23
from ethanol gave pale yellow crystals: mp 141–142 ꢁC; [
a]
D
þ48.1 (c 0.12, CHCl3). 1H NMR (360 MHz)
¼8.00–7.93 (m, 2H,
d
arom.), 7.60–7.51 (m, 3H, arom.), 7.47–7.32 (m, 5H, arom.), 7.20–7.10
(m, 5H, arom.), 5.55 (s, 1H, PhCH), 5.52 (dd, 1H, J¼8.4, 3.1 Hz, H-2),
4.88 (d, 1H, J¼12.7 Hz, PhCH2), 4.71 (d, 1H, J¼7.8 Hz, H-1), 4.67 (d,
1H, J¼12.7 Hz, PhCH2), 4.38 (d, 1H, J¼12.4 Hz, H-6a), 4.18 (dd, 1H,
J¼11.4, 3.2 Hz, H-3), 4.14–4.05 (m, 2H, H-4, H-6b), 3.69 (s, 1H, H-5),
the a and b anomers of 14 in a 4:1 ratio (0.39 g, 44%) as a syrup.
Anal. Calcd for C20H24O12S (488.46): C, 49.18; H, 4.95; S, 6.56.
Found: C, 49.01; H, 5.01; S, 6.51. MALDI-TOF: m/z calcd for [MþNa]þ
511.089. Found: 511.258.
2.23 (s, 3H, SCOCH3) ppm. 13C NMR (90 MHz)
d
¼195.29 (SCOCH3),
4.11. Ethyl 4,6-di-O-acetyl-2-O-benzoyl-3-deoxy-3-
methylsulfonato-1-thio-a,b-D-galactopyranose (15)
165.67 (PhC]O), 137.83, 137.55, 133.54, 130.35, 130.09, 129.47,
128.77, 128.67, 128.61, 128.13, 128.05, 126.70 (arom. Cs), 101.67
(PhCH), 101.06 (C-1), 76.25 (C-4), 70.19 (PhCH2), 69.49 (C-2), 69.43
(C-6), 68.93 (C-5), 47.28 (C-3), 30.90 (SCOCH3) ppm. Anal. Calcd for
C29H28O9S (520.59): C, 66.91; H, 5.42; S, 6.16. Found: C, 66.75; H,
5.52; S, 6.22. MALDI-TOF m/z calcd for [MþNa]þ 543.145. Found:
543.204.
To a solution of compound 14 (201 mg, 0.58 mmol) in dry
CH2Cl2 was added EtSH (128 L, 3 equiv). The mixture was cooled
to 0 ꢁC and BF3$OEt2 (143
L, 2 equiv) was added. The mixture was
m
m
stirred for 1 h, then diluted with CH2Cl2, washed three times with
water, dried (MgSO4) and concentrated. Column chromatography

Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
2409
(98:2 CH2Cl2–acetone, Rf 0.66) of the residue gave an unseparable
mixture of the and anomers of 15 in a 5:1 ratio (135 mg, 48%)
as a syrup. Anal. Calcd for C20H26O10S (490.54): C, 48.97; H, 5.34; S,
13.07. Found: C, 48.88; H, 5.36; S, 13.10.
(PhCH2), 71.06 (C-50), 70.70 (C-30), 69.62 (C-5), 69.57 (C-6), 68.39
(C-20), 66.70 (C-40), 61.36 (C-60), 53.80 (C-2), 23.92 (SCH2CH3),
20.48, 20.44, 20.30, 19.78 (4ꢃOCOCH3), 14.82 (SCH2CH3) ppm. Anal.
Calcd for C37H43O15NS (773.80): C, 57.43; H, 5.60; N, 1.81; S, 4.14.
Found: C, 57.39; H, 5.62; N, 1.83; S, 4.13. MALDI-TOF: m/z calcd for
[MþNa]þ 796.23. Found: 796.21.
a
b
4.12. Allyl 2-acetamido-3-O-(4,6-di-O-acetyl-2-O-benzoyl-3-
deoxy-3-methylsulfonato-a-D-galactopyranosyl)-4,6-O-
benzylidene-2-deoxy- -glucopyranoside (16)
b
-
D
4.14. Ethyl 3-O-(2,3,4,6-tetra-O-acetyl-
6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
deoxy-2-phthalimido-1-thio- -glucopyranoside (19)
b
-
D
-galactopyranosyl)-
b-D-arabinopyranosyl)-2-
Bromo sugar 5 was freshly prepared from 15 (70 mg, 0.14 mmol)
according to general method IV. To a stirred suspension of acceptor
8 (100 mg, 0.29 mmol, 2 equiv) in dry CH3NO2 (1 mL) and dry
toluene (2 mL) containing activated 3 Å molecular sieves (pow-
dered, 0.5 g) was added Hg(CN)2 (150 mg, 2 equiv) and the mixture
cooled to 0 ꢁC. The bromo sugar in dry CH3NO2 (1 mL) was added
via syringe and the mixture was stirred for 2 h when TLC showed
disappearance of the donor. The mixture was diluted with CH2Cl2
and filtered through a layer of Celite and the filtrate was washed
twice with aq KI (5%) and water, dried (MgSO4) and concentrated.
b-D
Bromo sugar 6 was prepared from thioglycoside donor (1.39 g,
3.0 mmol, 1.05 equiv) and coupled with acceptor 18 (2.21 g,
2.86 mmol) according to general method III. Column chromatog-
raphy of the residue (1:1 hexane–EtOAc) gave compound 19 (1.33 g,
52%) as a syrup and 18 (1.10 g, 33%) was also recovered. Compound
23
19: [a
]
ꢀ45 (c 0.13, CHCl3). 1H NMR (360 MHz)
¼7.90–7.73 (m,
d
D
4H, arom.), 7.48–7.17 (m, 20H, arom.), 5.25 (br d, 1H, J¼2.6 Hz), 5.18
(s, 1H), 5.08 (d, 1H, J¼10.4 Hz), 5.02 (t, 1H, J¼9.2 Hz), 4.95–4.63 (m,
7H), 4.59–4.44 (m, 3H), 4.43–4.32 (m, 2H), 4.26 (d, 1H, J¼8.4 Hz),
4.22–4.12 (m, 2H), 4.07–3.94 (m, 4H), 3.91 (s, 1H), 3.82 (d, 1H,
J¼12.8 Hz), 3.72–3.58 (m, 3H), 2.75–2.50 (m, 2H, SCH2CH3), 2.03,
1.97, 1.84, 1.60 (4ꢃs, 12H, 4ꢃOCOCH3), 1.15 (t, 3H, J¼7.4 Hz,
Column chromatography (96:4, CH2Cl2–MeOH) of the residue gave
23
compound 16 (44 mg, 40%) as a syrup: [
a]
þ20.5 (c 0.12, CHCl3).
D
1H NMR (500 MHz)
d
¼7.94 (d, 2H, J¼7.2 Hz, arom.), 7.60 (t, 1H,
J¼7.5 Hz, arom.), 7.51 (d, 2H, J¼6.6 Hz, arom.), 7.44 (t. 2H, J¼7.8 Hz,
arom.), 7.37–7.29 (m, 3H, arom.), 6.10 (d, 1H, J¼7.1 Hz, NHAc),
5.93–5.84 (m, 1H, OCH2CHCH2), 5.58 (d, 1H, J¼2.5 Hz, H-20), 5.53 (s,
1H, PhCH), 5.32–5.18 (m, 4H, H-1, H-10, OCH2CHCH2), 5.16–5.12 (m,
1H, H-50), 4.76 (dd, 1H, J¼7.8, 1.6 Hz, H-40), 4.57 (t, 1H, J¼9.4 Hz,
H-3), 4.37 (dd, 1H, J¼10.5, 4.7 Hz, H-6a), 4.36–4.31 (m, 1H,
OCH2CHCH2), 4.13–4.08 (m, 1H, OCH2CHCH2), 4.01–3.96 (m, 4H,
H-60a, OCH3), 3.76 (t, 1H, J¼10 Hz, H-6b), 3.67 (dd, 1H, J¼7.8 Hz,
J¼2.5 Hz, H-30), 3.62–3.56 (m, 1H, H-5), 3.54 (t, 1H, J¼9.1 Hz, H-4),
3.18 (td, 1H, J¼9.5, 7.9 Hz, H-2), 3.08 (dd, 1H, J¼12.2, 2.5 Hz, H-60b),
2.06 (s, 3H, OCOCH3), 1.94, 1.91 (2 s, 6H, OCOCH3, NHCOCH3) ppm.
SCH2CH3) ppm. 13C NMR (90 MHz)
d¼170.04, 169.98, 169.78, 169.43
(4ꢃOCOCH3), 138.86, 138.67, 138.46, 138.29, 134.84, 128.59, 128.44,
128.38, 127.80, 127.64, 127.58, 127.40, 127.24, 123.76 (arom. Cs),
100.24 (C-10, J¼161.8 Hz), 98.23 (C-100, J¼172.4 Hz), 80.89 (C-1,
J¼158.3 Hz), 80.08, 78.82, 75.94, 75.16, 74.02, 73.16, 70.38, 68.12,
66.39 (skeleton Cs), 74.98, 73.22, 72.09, 71.05 (overlap) (4ꢃPhCH2),
67.66 (C-6), 60.53, 59.92 (C-60, C-500), 55.31 (C-2), 23.46 (SCH2CH3),
20.63, 20.57, 20.50, 20.20 (4ꢃOCOCH3), 15.00 (SCH2CH3) ppm. Anal.
Calcd for C63H69O19NS (1176.28): C, 64.33; H, 5.91; N, 1.19; S, 2.73.
Found: C, 64.20; H, 6.01; N, 1.17; S, 2.69. MALDI-TOF: m/z calcd for
[MþNa]þ 1198.41. Found: 1198.41.
13C NMR (125 MHz)
d
¼171.07, 170.47, 170.02 (2ꢃOCOCH3,
NHCOCH3), 165.59 (OCOPh), 137.28, 133.99, 129.65, 129.10, 128.66,
128.52, 128.32, 126.39 (arom. Cs), 133.71 (OCH2CHCH2), 117.81
(OCH2CHCH2), 105.49 (C-10, J¼179 Hz), 101.94 (PhCH, J¼163 Hz),
98.93 (C-1, J¼167 Hz), 80.60 (C-4), 79.43 (C-2), 77.19 (C-40), 73.16
(C-3), 70.57 (OCH2CHCH2), 69.76 (C-50), 68.83 (C-6), 66.02 (C-5),
63.78 (C-30), 63.38 (C-6), 59.23 (C-2), 56.75 (OCH3), 23.44
(NHCOCH3), 20.70, 20.60 (2ꢃOCOCH3) ppm. Anal. Calcd for
C36H43O16NS (777.79): C, 55.59; H, 5.57; N, 1.80; S, 4.12. Found: C,
55.50; H, 5.62; N, 1.85; S, 4.05. MALDI-TOF: m/z calcd for [MþNa]þ
800.22. Found: 800.41.
4.15. Ethyl 3-O-(2,3,4,6-tetra-O-acetyl-
6-O-benzyl-4-O-(2,3,4-tri-O-benzyl- -fucopyranosyl)-2-
deoxy-2-phthalimido-1-thio- -glucopyranoside (20)
b-D-galactopyranosyl)-
a-L
b-D
Bromo sugar 7 was prepared from thioglycoside donor (4.78 g,
3.0 mmol, 1.5 equiv) and coupled with acceptor 18 (7.2 g, 9.3 mmol)
according to general method III. Column chromatography of the
residue (92:8 CH2Cl2–EtOAc) gave compound 20 (6.21 g, 56%) as
a syrup and 18 was also recovered (3.26 g, 27%). Compound 20 has
23
[a
]
ꢀ11.3 (c 0.20, CHCl3). IR nmax (KBr) 3434, 2932, 2872, 1755,
D
4.13. Ethyl 3-O-(2,3,4,6-tetra-O-acetyl-
b-D
-galactopyranosyl)-
1715, 1611, 1427, 1388, 1315, 1031, 952, 912, 736, 721, 698, 600 cmꢀ1
1H NMR (360 MHz)
¼7.92–7.76 (m, 4H, arom.), 7.47 (d, 2H,
;
6-O-benzyl-2-deoxy-2-phthalimido-1-thio-
b-
D-
d
glucopyranoside (18)
J¼7.8 Hz, arom.), 7.40–7.20 (m, 18H, arom.), 5.25–5.19 (m, 2H), 5.06
(d, 1H, J¼10.5 Hz, H-1), 5.07–4.97 (m, 2H, H-20, PhCH2), 4.94–4.71
(m, 7H, H-3, H-500, PhCH2), 4.48–4.41 (m, 3H, H-30, PhCH2), 4.37 (t,
1H, J¼10.3 Hz, H-2), 4.30–4.17 (m, 3H, H-10, H-20, H-60a), 4.07–3.95
(m, 4H, H-300, H-4, H-6a, H-60b), 3.79 (s, 1H, H-400), 3.74–3.59 (m, 3H,
H-5, H-50, H-6b,), 2.76–2.50 (m, 2H, SCH2CH3), 2.02, 2.00, 1.84, 1.73
(4ꢃs, 12H, 4ꢃOCOCH3), 1.33 (d, 3H, J¼6.3 Hz, CH3-600), 1.17 (t, 3H,
Prepared from 17 (2.05 g, 2.66 mmol) according to general
method II and purified by column chromatography (95:5 CH2Cl2–
23
acetone) to give compound 18 (1.58 g, 77%) as a syrup: [
a
]
ꢀ10.3
D
(c 0.18, CHCl3). IR nmax (KBr) 3477, 2930, 2871, 1752, 1715, 1468,
1453, 1428, 1386, 1219, 1172, 1136, 1078, 969, 736, 722, cmꢀ1 1H
NMR (360 MHz)
;
d
¼7.94–7.72 (m, 4H, arom.), 7.40–7.22 (m, 5H,
J¼7.4 Hz, SCH2CH3) ppm. 13C NMR (90 MHz)
d
¼169.85, 169.72,
arom.), 5.29 (d, 1H, J¼3.0 Hz, H-40), 5.16 (d, 1H, J¼10.5 Hz, H-1), 5.14
(dd, 1H, J¼10.6 Hz, J¼8 Hz, H-20), 4.80 (dd, 1H, J¼10.5 Hz, J¼3.4 Hz,
H-30), 4.67–4.59 (m, 2H, PhCH2), 4.55–4.47 (m, 1H, H-3), 4.40 (d, 1H,
J¼8 Hz, H-10), 4.33 (t, 1H, J¼10.4 Hz, H-2), 4.14–4.07 (m, 2H,
H-60a,b), 3.99–3.88 (m, 3H, H-50, H-6a, OH), 3.77–3.71 (m, 1H, H-
6b), 3.70–3.62 (m, 2H, H-5, H-4), 2.76–2.56 (m, 2H, SCH2CH3), 2.13,
2.04, 1.88, 1.53 (4ꢃs, 12H, 4ꢃOCOCH3), 1.18 (t, 3H, J¼7.4 Hz,
169.57, 169.07 (4ꢃOCOCH3), 138.58, 138.48, 138.10, 134.59, 128.56,
128.23, 128.10, 127.63, 127.46, 127.28, 127.17, 126.79, 123.50 (arom.
Cs), 100.34 (C-10, J¼161.7 Hz), 97.51 (C-100, J¼170.9 Hz), 80.68 (C-3),
80.57 (C-1, J¼153.1 Hz), 79.91 (C-5), 76.15 (C-400), 75.53 (C-200), 75.30
(C-300), 72.50 (C-4), 70.86 (C-30), 70.06 (C-50), 67.64 (C-20), 66.13
(double int., C-40, C-500), 74.72, 73.72, 72.90, 72.05 (4ꢃPhCH2), 67.23
(C-6), 59.54 (C-60), 55.05 (C-2), 23.25 (SCH2CH3), 20.40, 20.27
(double int.), 20.23 (4ꢃOCOCH3), 16.80 (C-600), 14.77 (SCH2CH3)
ppm. Anal. Calcd for C64H71O19NS (1190.31): C, 64.58; H, 6.01; N,
1.18; S, 2.69. Found: C, 64.50; H, 6.05; N,1.19; S, 2.71. MALDI-TOF: m/z
calcd for [MþNa]þ 1212.42. Found: 1212.55.
SCH2CH3) ppm. 13C NMR (90 MHz)
d
¼170.28, 169.98, 169.85, 168.75
(4ꢃOCOCH3), 168.42, 167.14 (2ꢃC]O, NPhth), 138.29, 134.43,
131.43,131.34,128.22,127.46,123.71,123.58 (arom. Cs),100.89 (C-10,
J¼162.4 Hz), 82.84 (C-3), 80.95 (C-1, J¼157.6 Hz), 79.79 (C-4), 73.37

2410
Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
4.16. Ethyl 6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
b
-
D
-
J¼158.6 Hz), 79.96, 77.89, 76.81, 75.40, 75.07, 74.78, 73.53, 72.03,
70.53, 66.39 (skeleton Cs), 74.73, 72.90, 71.56, 70.48 (4ꢃPhCH2),
68.94, 67.37 (C-6, C-60), 60.92 (C-500), 55.13 (C-2), 23.49 (SCH2CH3),
14.85 (SCH2CH3) ppm. Anal. Calcd for C62H65O15NS (1096.24): C,
67.93; H, 5.98; N, 1.28; S, 2.92. Found: C, 67.78; H, 6.02; N, 1.30; S,
2.96. MALDI-TOF: m/z calcd for [Mþ2Na]þ 1141.39. Found: 1142.71.
arabinopyranosyl)-2-deoxy-3-O-(
b-D-galactopyranosyl)-2-
phthalimido-1-thio- -glucopyranoside (21)
b-D
To a solution of compound 19 (880 mg, 0.75 mmol) in dry THF
(10 mL) and dry CH2Cl2 (10 mL) was added three drops of NaOCH3
(30% in MeOH) and the reaction stirred for 1 h. The mixture was
neutralized with Amberlite IR-120Hþ cation exchange resin, fil-
tered and concentrated. Column chromatography of the residue
4.19. Ethyl 6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
a-L-
fucopyranosyl)-3-O-(4,6-O-benzylidene-
b-D-
(94:6 CH2Cl2–MeOH) gave compound 21 (679 mg, 90%) as a syrup:
galactopyranosyl)-2-deoxy-2-phthalimido-1-thio-
glucopyranoside (24)
b-D-
23
[
a]
ꢀ45.1 (c 0.13, CHCl3). 1H NMR (360 MHz)
¼7.88–7.66 (m, 4H,
d
D
arom.), 7.36–7.19 (m, 20H, arom.), 5.24–5.15 (m, 2H), 4.82 (t, 1H,
J¼9.7 Hz), 4.76 (d, 1H, J¼10.7 Hz), 4.68–4.53 (m, 6H), 4.36 (s, 2H),
4.38 (t, 1H, J¼10.4 Hz), 4.19–4.10 (m, 2H), 4.02 (t, 1H, J¼9.4 Hz),
3.93–3.46 (m, 13H), 3.30–3.07 (m, 3H), 2.73–2.52 (m, 2H, SCH2CH3),
Prepared from 22 (3.68 g, 3.6 mmol) according to general
method I. Column chromatography of the residue (7:3 EtOAc–
23
hexane) gave compound 24 (3.79 g, 78%) as a syrup: [
a
]
ꢀ47
D
1.17 (t, 3H, J¼7.4 Hz, SCH2CH3) ppm. 13C NMR (90 MHz)
d
¼138.58,
(c 0.13, CHCl3). 1H NMR (360 MHz)
d¼7.93–7.64 (m, 4H, arom.), 7.51
138.34, 138.11, 134.32, 128.35, 128.28, 127.78, 127.71, 127.54 (arom.
Cs), 101.69 (C-10), 97.88 (C-100), 80.97 (C-1), 79.51, 76.11, 75.35, 74.61,
74.05, 73.62, 73.16, 70.36, 69.50 (skeleton Cs), 74.46, 73.04, 72.08,
71.61 (4ꢃPhCH2), 68.26 (C-6), 62.99, 61.37 (C-60, C-500), 54.95 (C-2),
23.76 (SCH2CH3), 14.93 (SCH2CH3) ppm. Anal. Calcd for
C55H61O15NS (1008.14): C, 65.53; H, 6.10; N, 1.39; S, 3.18. Found: C,
65.48; H, 6.13; N, 1.41; S, 3.15. MALDI-TOF: m/z calcd for [MþNa]þ
1030.37. Found: 1030.72.
(d, 2H, J¼7.7 Hz, arom.), 7.36–7.13 (m, 23H, arom.), 5.55 (s, 1H,
PhCH), 5.21 (dd, 1H, J¼10.4, 2.3 Hz), 5.08 (s, 1H), 4.88–4.52 (m, 6H),
4.42–4.36 (m, 3H), 4.27 (dd, 2H, J¼22.7 Hz, J¼11.7 Hz), 4.04–3.89
(m, 7H), 3.73–3.54 (m, 4H), 3.31 (s, 1H), 3.26 (s, 1H), 3.13 (dd, 1H,
J¼9.3, 2.9 Hz), 2.75–2.51 (m, 4H, 2ꢃOH, SCH2CH3), 1.17 (t, 3H,
J¼7.4 Hz, SCH2CH3), 1.04 (d, 3H, J¼6.3 Hz, CH3-600) ppm. 13C NMR
(90 MHz)
d
¼168.85, 168.16 (2ꢃC]O, NPhth), 139.24, 139.01, 138.30,
138.17, 137.47, 134.56, 134.03, 131.78, 130.86, 128.78, 128.63, 128.10,
127.77, 127.49, 127.37, 127.27, 127.20, 127.08, 126.84, 125.57, 124.09,
123.03 (arom. Cs), 103.50 (PhCH, J¼157.6 Hz), 99.75 (C-10,
J¼168.3 Hz), 97.80 (C-100, J¼173.6 Hz), 80.60 (C-1, J¼159.2 Hz), 80.01,
79.49, 78.43, 76.88, 75.00, 74.91, 72.92, 72.12, 70.68, 66.55, 66.08
(skeleton Cs), 74.77, 74.61, 72.81, 71.03 (4ꢃPhCH2), 69.06, 67.30
(C-6, C-60), 55.29 (C-2), 23.35 (SCH2CH3), 16.30 (C-600), 14.92
(SCH2CH3) ppm. Anal. Calcd for C63H67O15NS (1110.27): C, 68.15; H,
6.08; N, 1.26; S, 2.89. Found: C, 68.03; H, 6.12; N, 1.28; S, 2.87.
MALDI-TOF: m/z calcd for [MþNa]þ 1132.41. Found: 1132.59.
4.17. Ethyl 6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
fucopyranosyl)-2-deoxy-3-O-( -galactopyranosyl)-2-
phthalimido-1-thio- -glucopyranoside (22)
a-L-
b-D
b-D
Prepared from 20 (6.19 g, 5.21 mmol) in a similar manner as
described in Section 4.16. Column chromatography of the residue
23
(neat EtOAc) gave compound 22 (4.69 g, 88%) as a syrup: [a]
D
ꢀ43.8 (c 0.19, CHCl3). 1H NMR (360 MHz)
¼7.83–7.58 (m, 4H,
d
arom.), 7.42–7.15 (m, 20H, arom.), 5.20 (bd, 1H, J¼2.3 Hz), 5.11 (d,
1H, J¼10.3 Hz, H-1), 4.93 (d, 1H, J¼11.2 Hz), 4.86–4.50 (m, 7H), 4.44
(s, 2H), 4.39 (t, 1H, J¼10.4 Hz), 4.10–3.58 (m, 11H), 3.42–2.98 (m,
7H), 2.73–2.50 (m, 2H, SCH2CH3), 1.16 (t, 3H, J¼7.2 Hz, SCH2CH3),
4.20. Ethyl 6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
arabinopyranosyl)-3-O-(4,6-O-benzylidene-3-O-chloroacetyl-
-galactopyranosyl)-2-deoxy-2-phthalimido-1-thio-
glucopyranoside (25)
b-D-
b-D
b-D-
1.09 (d, 3H, J¼5.8 Hz, CH3-600) ppm. 13C NMR (90 MHz)
¼138.86,
d
138.80, 138.17, 138.04, 128.50, 128.32, 128.25, 128.06, 127.74, 127.51,
127.42, 127.35, 127.24 (arom. Cs), 101.96 (C-10, J¼158.2 Hz), 97.16 (C-
100, J¼168.7 Hz), 80.87 (C-1, J¼159.9 Hz), 79.62 (double int.), 77.92,
76.27, 75.91, 74.12, 73.44, 72.92, 70.74, 69.02, 66.74 (skeleton Cs),
74.90, 74.59, 73.00, 72.08 (4ꢃPhCH2), 67.89 (C-6), 62.65 (C-60),
55.08 (C-2), 23.63 (SCH2CH3), 16.60 (C-600), 14.92 (SCH2CH3) ppm.
Anal. Calcd for C56H63O15NS (1022.16): C, 65.80; H, 6.21; N, 1.37; S,
3.14. Found: C, 65.69; H, 6.28; N, 1.35; S, 3.12. MALDI-TOF: m/z calcd
for [MþNa]þ 1044.38. Found: 1044.57.
A solution of compound 23 (569 mg, 0.52 mmol) and Bu2SnO
(168 mg,1.3 equiv) in dry toluene (15 mL) was stirred using a Dean–
Stark apparatus containing activated 4 Å molecular sieves at reflux
for 3 h. The mixture was concentrated and dried under high
vacuum for 3 h. To a solution of the crude acetal in dry DMF (3 mL)
and dry toluene (2 mL) containing activated 4 Å molecular sieves
was added chloroacetyl chloride (50 m
L, 1.05 equiv) at 0 ꢁC. After
stirring for 1 h the mixture was filtered through Celite, concen-
trated and coevaporated twice with toluene. Column chromatog-
4.18. Ethyl 6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
arabinopyranosyl)-3-O-(4,6-O-benzylidene-
galactopyranosyl)-2-deoxy-2-phthalimido-1-thio-
glucopyranoside (23)
b
-
D
-
raphy of the residue (96:4 CH2Cl2–acetone) gave compound 25
23
b-D
-
(475 mg, 78%) as a syrup: [
a
]
ꢀ18.3 (c 0.12, CHCl3). IR nmax (KBr)
D
b
-
D
-
3014, 2969, 2358, 2341, 1736, 1364, 1228, 1216, 1107, 903, 527,
516 cmꢀ1 1H NMR (360 MHz)
;
d
¼7.88–7.79 (m, 2H), 7.72–7.65 (m,
2H), 7.47–7.40 (m, 2H), 7.35–7.14 (m, 23H), 5.43 (s, 1H, PhCH), 5.21
(d, 1H, J¼7.4 Hz), 5.16 (d, 1H, J¼3.2 Hz), 4.88–4.77 (m, 2H), 4.69–
4.33 (m, 8H), 4.27–3.78 (m, 13H), 3.65 (dd, 2H, J¼20.6, 10.3 Hz),
3.51–3.42 (m, 2H), 3.28 (s,1H), 2.82 (br s,1H, OH), 2.73–2.50 (m, 2H,
SCH2CH3), 1.16 (t, 3H, J¼7.4 Hz, SCH2CH3) ppm. 13C NMR (90 MHz)
Prepared from 21 (1.216 g, 1.21 mmol) according to general
method I. Column chromatography of the residue (96:4 CH2Cl2–
MeOH) gave compound 23 (1.12 g, 85%) as a syrup: [
23
a
]
ꢀ59 (c
D
0.19, CHCl3). 1H NMR (360 MHz)
d
¼7.90–7.65 (m, 4H, arom.), 7.44–
7.14 (m, 25H, arom.), 5.45 (s, 1H, PhCH), 5.20 (d, 1H, J¼10.4 Hz, H-1),
5.16 (d, 1H, J¼3.4 Hz), 4.85 (d, 1H, J¼11.5 Hz), 4.76 (t, 1H, J¼9.7 Hz),
4.68–4.35 (m, 7H), 4.12 (d, 1H, J¼12.1 Hz), 4.03–3.82 (m, 9H), 3.71–
3.42 (m, 5H), 3.18 (s, 1H), 3.10 (dd, 1H, J¼9.3, 2.8 Hz), 2.89 (br s, 1H,
OH), 2.80–2.50 (m, 3H, OH, SCH2CH3), 1.17 (t, 3H, J¼7.4 Hz,
d¼168.70, 168.07 (2ꢃC]O, NPhth), 166.81 (COCH2Cl), 139.10,
138.84, 138.30, 138.03, 137.40, 134.53, 134.21, 128.76, 128.35, 128.06,
127.79, 127.40, 127.33, 127.26, 127.20, 127.05, 126.88, 126.79, 125.50,
123.89, 123.19 (arom. Cs), 102.55 (PhCH, J¼156.2 Hz), 99.77 (C-10,
J¼158.3 Hz), 98.27 (C-100, J¼173.7 Hz), 80.65 (C-1, J¼153.6 Hz),
79.84, 77.76, 76.56, 75.34, 75.07, 74.86, 73.56, 72.35, 67.41, 66.00
(skeleton Cs), 74.69, 72.85, 71.52, 70.57 (4ꢃPhCH2), 68.74, 67.28
(C-6, C-60), 60.89 (C-500), 55.06 (C-2), 40.58 (COCH2Cl), 23.45
(SCH2CH3), 14.83 (SCH2CH3) ppm. Anal. Calcd for C64H66O16NSCl
SCH2CH3) ppm. 13C NMR (90 MHz)
d¼168.82, 168.01 (2ꢃC]O,
NPhth), 139.15, 138.89, 138.37, 138.09, 137.57, 128.40, 128.09, 127.82,
127.38, 127.56, 126.95, 125.70 (arom. Cs), 102.83 (PhCH, J¼157.4 Hz),
100.09 (C-10, J¼162.3 Hz), 98.26 (C-100, J¼170.9 Hz), 80.75 (C-1,

Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
2411
(1172.72): C, 65.55; H, 5.67; N,1.19; S, 2.73; Cl, 3.02. Found: C, 65.42;
4.23. Ethyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-benzylidene-
3-O-chloroacetyl- -galactopyranosyl)-4-O-(2,3,4-tri-O-
benzyl- -fucopyranosyl)-2-deoxy-2-phthalimido-1-thio-
-glucopyranoside (28) and ethyl 6-O-benzyl-3-O-(2-O-
benzoyl-4,6-O-benzylidene- -galactopyranosyl)-4-O-(2,3,4-
tri-O-benzyl- -fucopyranosyl)-2-deoxy-2-phthalimido-1-
thio- -glucopyranoside (29)
H, 5.73; N, 1.20; S, 2.69. MALDI-TOF: m/z calcd for [MþNa]þ 1194.37.
b-D
Found: 1194.46.
a
-L
b-
D
b-D
4.21. Ethyl 6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
a-
L-
a-L
fucopyranosyl)-3-O-(4,6-O-benzylidene-3-O-chloroacetyl-
b-D
-
b-D
galactopyranosyl)-2-deoxy-2-phthalimido-1-thio-
glucopyranoside (26)
b-D-
Prepared from 26 (3.146 g, 2.65 mmol) in a similar manner as
described in Section 4.22, but the mixture was stirred for 3 h.
Column chromatography of the residue (98:2 CH2Cl2–acetone) gave
Prepared from 24 (3.78 g, 3.40 mmol) in a similar manner as
described in Section 4.20. Column chromatography of the residue
compound 28 (1.494 g, 44%) as a syrup and dechloroacetylated
23
(9:1 CH2Cl2–EtOAc) gave compound 26 (3.20 g, 79%) as a syrup:
derivative 29 (1.148 g, 34%) as a syrup. Compound 28: [
(c 0.14, CHCl3). IR nmax (KBr) 2929, 2868,1776,1737,1715,1495,1452,
a
]
þ1.5
D
23
[
a]
ꢀ10.6 (c 0.21, CHCl3). 1H NMR (360 MHz)
d
¼7.86 (dd, 2H,
D
J¼15.8 Hz, J¼6.0 Hz, arom.), 7.75–7.65 (m, 2H, arom.), 7.49 (d, 2H,
J¼7.1 Hz, arom.), 7.37–7.12 (m, 23H), 5.50 (s, 1H, PhCH), 5.22 (d, 1H,
J¼10.4 Hz), 5.11 (d, 1H, J¼3.1 Hz), 4.88–4.74 (m, 3H), 4.71–4.57
(m, 3H), 4.48–4.25 (m, 6H), 4.22 (d, 1H, J¼11.2 Hz), 4.14–3.89
(m, 8H), 3.85 (t, 1H, J¼8.8 Hz), 3.65 (dd, 2H, J¼20.5, 10.3 Hz), 3.52
(d, 1H, J¼11.3 Hz), 3.32 (s, 1H), 3.25 (s, 1H), 2.75–2.51 (m, 3H, OH,
SCH2CH3), 1.17 (t, 3H, J¼7.4 Hz, SCH2CH3), 1.06 (d, 3H, J¼6.3 Hz,
1383, 1365, 1314, 1263, 1167, 1136, 1092, 1059, 1002, 952, 737, 712,
697 cmꢀ1
;
1H NMR (360 MHz)
d¼7.91–7.69 (m, 5H, arom.), 7.64
(t, 1H, J¼7.4 Hz, arom.), 7.58–7.42 (m, 5H, arom.), 7.37–7.16
(m, 23H), 5.60 (dd, 1H, J¼10.6, 8.7 Hz), 5.58 (s, 1H, PhCH), 5.10
(d, 1H, J¼3.3 Hz), 5.01–4.79 (m, 5H), 4.65 (d, 1H, J¼11.6 Hz), 4.62
(s, 2H), 4.53–4.44 (m, 2H), 4.41–4.34 (m, 3H), 4.31 (t,1H, J¼10.5 Hz),
4.18–4.10 (m, 2H), 4.04–3.89 (m, 5H), 3.79 (d, 1H, J¼15.2 Hz),
3.67–3.52 (m, 3H), 3.46 (s, 1H), 3.20 (s, 1H), 2.66–2.37 (m, 2H,
SCH2CH3), 1.37 (d, 3H, J¼6.4 Hz, CH3-600), 1.07 (t, 3H, J¼7.4 Hz,
CH3-600) ppm. 13C NMR (90 MHz)
d
¼168.82, 168.30 (2ꢃC]O,
NPhth), 166.87 (COCH2Cl), 139.21, 138.99, 138.26, 138.13, 137.40,
134.70, 134.28, 131.57, 130.76, 128.75, 128.61, 128.09, 127.77, 127.49,
127.34, 127.27, 127.21, 127.14, 126.84, 125.46, 124.04, 123.24 (arom.
Cs), 102.91 (PhCH, J¼158.6 Hz), 99.50 (C-10, J¼160.5 Hz), 97.84 (C-100,
J¼169.9 Hz), 80.52 (C-1, J¼155.7 Hz), 79.94, 79.43, 78.42, 76.90,
74.97 (double int.), 72.96, 72.37, 67.51, 66.10, 66.05 (skeleton Cs),
74.74, 74.60, 72.84, 71.06 (4ꢃPhCH2), 68.89, 67.22 (C-6, C-60), 55.27
(C-2), 40.65 (COCH2Cl), 23.32 (SCH2CH3), 16.28 (C-600), 14.93
(SCH2CH3) ppm. Anal. Calcd for C65H68O16NSCl (1186.75): C, 65.78;
H, 5.78; N, 1.18; S, 2.70; Cl, 2.99. Found: C, 65.70; H, 5.80; N, 1.16; S,
2.72. MALDI-TOF: m/z calcd for [MþNa]þ 1208.38. Found: 1208.57.
SCH2CH3) ppm. 13C NMR (90 MHz)
d¼167.02 (O]CCH2Cl), 164.88
(PhC]O), 139.44, 139.22, 138.33, 137.18, 134.33, 133.12, 131.30,
129.81, 129.33, 128.98, 128.78, 128.16, 128.08, 127.79, 127.53, 127.47,
127.30, 127.19, 127.07, 126.85, 125.67 (arom. Cs), 100.34 (PhCH,
J¼159.1 Hz), 99.70 (C-10, J¼157.3 Hz), 97.94 (C-100, J¼170 Hz), 80.61
(C-1, J¼156.8 Hz), 80.23, 79.65, 78.93, 75.75, 75.17, 73.73, 73.00,
72.93, 68.65, 66.33, 66.28 (skeleton Cs), 74.89, 74.71, 72.83, 71.19
(4ꢃPhCH2), 69.00, 67.26 (C-6, C-60), 55.10 (C-2), 40.27 (COCH2Cl),
22.96 (SCH2CH3), 16.27 (C-600), 14.82 (SCH2CH3) ppm. Anal. Calcd for
C72H72O17NSCl (1290.86): C, 66.99; H, 5.62; N, 1.09; S, 2.48; Cl, 2.75.
Found: C, 66.89; H, 5.66; N, 1.11; S, 2.46. MALDI-TOF: m/z calcd for
[MþNa]þ 1312.41. Found: 1312.79.
23
4.22. Ethyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-benzylidene-
Compound 29: [
a]
ꢀ6.6 (c 0.12, CHCl3). IR nmax (KBr) 3454,
D
3-O-chloroacetyl-
benzyl- -arabinopyranosyl)-2-deoxy-2-phthalimido-1-thio-
-glucopyranoside (27)
b
-D-galactopyranosyl)-4-O-(2,3,4-tri-O-
2969, 2918, 1736, 1434, 1364, 1227, 1216, 528 cmꢀ1
;
1H NMR
b-
D
(360 MHz)
d
¼7.90–7.66 (m, 6H, arom.), 7.62 (t, 1H, J¼7.4 Hz, arom.),
b-
D
7.54 (d, 2H, J¼7.6 Hz, arom.), 7.47 (t, 2H, J¼7.6 Hz, arom.), 7.36–7.15
(m, 23H), 5.61 (s, 1H, PhCH), 5.35 (t, 1H, J¼9.0 Hz), 5.08 (br d, 1H,
J¼2.3 Hz), 4.97 (t, 2H, J¼10.9 Hz), 4.87 (d, 1H, J¼6.6 Hz), 4.83 (d, 1H,
J¼11.5 Hz), 4.65 (d, 1H, J¼11.6 Hz), 4.60 (s, 2H), 4.46 (d, 1H,
J¼12.4 Hz), 4.41–4.32 (m, 4H), 4.20 (d, 1H, J¼11.2 Hz), 4.12–4.06 (m,
2H), 4.03–3.92 (m, 4H), 3.66–3.57 (m, 3H), 3.43 (dt, 1H, J¼10.4,
3.5 Hz), 3.37 (s, 1H), 3.25 (s, 1H), 2.69–2.42 (m, 3H, OH, SCH2CH3),
1.31 (d, 3H, J¼6.3 Hz, CH3-600), 1.09 (t, 3H, J¼7.4 Hz, SCH2CH3) ppm.
To a solution of compound 25 (218 mg, 0.19 mmol) in dry CH2Cl2
(4 mL) and in dry pyridine (0.5 mL) was added BzCl (30 L,
m
1.1 equiv) at 0 ꢁC. The reaction only started when DMAP (1 equiv)
was added to the mixture. After half an hour the mixture was
diluted with CH2Cl2, washed with 1 M HCl, water, satd aq NaHCO3
and water again, dried (MgSO4) and concentrated. Column chro-
matography of the residue (1:1 EtOAc–hexane) gave compound 27
13C NMR (90 MHz)
d
¼166.39 (PhC]O), 139.40, 139.20, 138.31,
23
(191 mg, 80%) as a syrup: [
a]
ꢀ1.5 (c 0.13, CHCl3). IR nmax (KBr)
137.23, 134.32, 132.99, 131.42, 129.97, 129.67, 129.00, 128.76, 128.16,
128.11, 128.06, 127.80, 127.53, 127.47, 127.27, 127.22, 127.06, 126.87,
125.62 (arom. Cs), 100.03 (PhCH, J¼159.9 Hz), 99.93 (C-10,
J¼165.2 Hz), 97.91 (C-100, J¼169.8 Hz), 80.70 (C-1, J¼156.5 Hz),
80.24, 79.64, 78.89, 75.58, 75.09 (triple int.), 72.91, 72.10, 71.97,
66.61, 66.30 (skeleton Cs), 74.90, 74.69, 72.81, 71.21 (4ꢃPhCH2),
69.08, 67.29 (C-6, C-60), 55.15 (C-2), 22.98 (SCH2CH3), 16.52 (C-600),
14.82 (SCH2CH3) ppm. Anal. Calcd for C70H71O16NS (1214.37): C,
69.23; H, 5.89; N, 1.15; S, 2.64. Found: C, 69.18; H, 5.92; N, 1.13; S,
2.66. MALDI-TOF: m/z calcd for [MþNa]þ 1236.44. Found: 1236.74.
D
2867, 1774, 1715, 1452, 1383, 1366, 1264, 1139, 1092, 737, 720,
697 cmꢀ1 1H NMR (360 MHz)
;
d
¼7.82–7.73 (m, 4H, arom.), 7.46
(t, 4H, J¼7.2 Hz, arom.), 7.36–7.16 (m, 26H), 5.59 (t, 1H, J¼9.2 Hz),
5.51 (s, 1H, PhCH), 5.17 (d, 1H, J¼2.8 Hz), 5.03–4.91 (m, 2H), 4.88–
4.78 (m, 2H), 4.71 (d, 1H, J¼12.6 Hz), 4.61–4.40 (m, 6H), 4.38–4.26
(m, 3H), 4.11–3.56 (m, 12H), 3.44–3.37 (m, 2H), 2.67–2.38 (m, 2H,
SCH2CH3), 1.07 (t, 3H, J¼7.4 Hz, SCH2CH3) ppm. 13C NMR (90 MHz)
d
¼166.95 (COCH2Cl), 164.94 (PhC]O), 139.37, 139.20, 138.41,
138.22, 137.15, 134.37, 133.15, 131.31, 129.83, 129.30, 128.92, 128.61,
128.20, 128.11, 128.06, 127.84, 127.41, 127.27, 126.96, 126.75, 125.56
(arom. Cs), 100.07 (PhCH, J¼153.4 Hz), 99.82 (C-10, J¼161.6 Hz),
98.38 (C-100, J¼170.8 Hz), 80.69 (C-1, J¼153.4 Hz), 80.17, 78.13, 75.60
(double int.), 75.23, 73.54, 73.35, 72.95, 68.65, 66.26 (skeleton Cs),
74.86, 72.91, 71.64, 70.57 (4ꢃPhCH2), 68.93, 67.33 (C-6, C-60), 60.72
(C-500), 55.13 (C-2), 40.24 (COCH2Cl), 23.11 (SCH2CH3), 14.77
(SCH2CH3) ppm. Anal. Calcd for C71H70O17NSCl (1276.83): C, 66.79;
H, 5.53; N, 1.10; S, 2.51; Cl, 2.78. Found: C, 66.68; H, 5.54; N, 1.12; S,
2.50. MALDI-TOF: m/z calcd for [MþNa]þ 1298.40. Found: 1298.51.
4.24. Methyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-
benzylidene-3-O-chloroacetyl-
(2,3,4-tri-O-benzyl- -arabinopyranosyl)-2-deoxy-2-
phthalimido- -glucopyranoside (30)
b-D-galactopyranosyl)-4-O-
b-D
b-D
A solution of compound 27 (253 mg, 0.2 mmol) in dry CH2Cl2
(3 mL) containing activated 3 Å molecular sieves was added dry
MeOH (34
m
L, 4 equiv) and the reaction stirred at ꢀ70 ꢁC for 2 h.

2412
Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
23
A mixture of NIS (44 mg,1.3 equiv) and TMSOTf (8
m
L, 0.25 equiv) in
[a
]
ꢀ6.6 (c 0.12, CHCl3). IR nmax (KBr) 3443, 2916, 2864, 1777,
D
dry THF (0.5 mL) was added via syringe, stirred for overnight and
allowed to reach rt. Pyridine (100 L) was added to the reaction and
1715, 1602, 1495, 1467, 1452, 1387, 1363, 1316, 1266, 1214, 1171, 1097,
1055, 1027, 1000, 903, 873, 821, 735, 722, 697 cmꢀ1 1H NMR
(360 MHz)
m
;
the mixture was diluted with CH2Cl2, filtered through Celite. The
filtrate was washed with satd aq Na2S2O3, water, satd aq NaHCO3,
again with water, dried (MgSO4) and concentrated. Column chro-
d
¼7.94–7.16 (m, 34H), 5.60 (s, 1H, PhCH), 5.34 (t, 1H,
J¼8.9 Hz), 5.08 (s, 1H), 4.97 (t, 1H, J¼9.9 Hz), 4.90–4.77 (m, 3H),
4.67–4.58 (m, 3H), 4.50–4.35 (m, 5H), 4.30–3.90 (m, 7H), 3.68–3.53
(m, 3H), 3.47–3.19 (m, 6H), 2.62 (br s, 1H, OH), 1.30 (d, 3H, J¼5.9 Hz,
matography of the residue (98:2 CH2Cl2–acetone) gave compound
23
30 (228 mg, 90%) as a syrup: [
a
]
ꢀ5.9 (c 0.10, CHCl3). IR nmax
CH3-600) ppm. 13C NMR (90 MHz)
d
¼166.51 (PhC]O), 139.42,
D
(KBr) 3747, 3062, 3030, 2865, 1775, 1715, 1633, 1496, 1467, 1220,
1139, 1091, 1052, 1027, 1000, 908, 787, 738, 712, 698, 639, 530 cmꢀ1
1H NMR (360 MHz)
139.20, 138.36, 138.25, 137.29, 134.25, 132.95, 131.44, 129.96, 129.63,
128.98, 128.72, 128.14, 127.80, 127.43, 127.35, 127.22, 127.07, 126.85,
125.63, 123.52 (arom. Cs), 99.95 (double int.), 98.73 (PhCH, C-1, C-
10), 97.85 (C-100, J 170.9 Hz), 79.62, 78.83, 75.66 (double int.), 75.29,
73.70, 73.06, 72.13, 72.00, 66.60, 66.30 (skeleton Cs), 74.85, 74.72,
72.84, 71.19 (4ꢃPhCH2), 69.09, 67.03 (C-6, C-60), 55.99 (double
;
d
¼7.79–7.58 (m, 7H, arom.), 7.50–7.18 (m, 27H),
5.58 (t, 1H, J¼9.5 Hz, J¼8.9 Hz), 5.51 (s, 1H, PhCH), 5.16 (d, 1H,
J¼2.7 Hz), 4.95 (t, 1H, J¼9.9 Hz), 4.88–4.77 (m, 3H), 4.70 (d, 1H,
J¼12.5 Hz), 4.57–4.29 (m, 8H), 4.21 (t, 1H, J¼10.2 Hz, J¼8.9 Hz),
4.10–3.78 (m, 8H), 3.78–3.52 (m, 4H), 3.40 (s, 2H), 3.25 (s, 3H, OCH3)
int.)(OCH3, C-2), 16.51 (C-600) ppm. Anal. Calcd for C69H69O17
N
ppm. 13C NMR (90 MHz)
d
¼166.89 (COCH2Cl), 164.95 (PhC]O),
(1184.28): C, 69.98; H 5.87, N 1.18. Found: C 69.87, H 5.94, N 1.15.
139.36, 139.16, 138.42, 138.12, 137.15, 134.25, 133.04, 131.28, 129.76,
129.27, 128.87, 128.52, 128.10, 127.80, 127.47, 127.39, 127.25, 126.98,
126.90, 126.71, 125.53, 123.51 (arom. Cs), 99.95, 99.75, 98.61, 98.27
(PhCH, C-1, C-10, C-100), 78.06, 75.65, 75.57, 75.47, 73.84, 73.46
(double int.), 68.88, 66.18 (skeleton Cs), 74.83, 72.91, 71.48, 70.49
(4ꢃPhCH2), 68.88, 67.03 (C-6, C-60), 60.57 (C-500), 56.01, 55.15
(OCH3, C-2), 40.21 (COCH2Cl) ppm. Anal. Calcd for C70H68O18NCl
(1246.74): C, 67.44; H, 5.50; N, 1.12; Cl, 2.84. Found: C, 67.32; H,
5.56; N, 1.14. MALDI-TOF: m/z calcd for [MþNa]þ 1268.40. Found:
1268.59.
MALDI-TOF: m/z calcd for [MþNa]þ 1206.45. Found: 1206.41.
4.27. Methyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-
benzylidene-b-D-gulopyranosyl)-4-O-(2,3,4-tri-O-benzyl-b-D-
arabinopyranosyl)-2-deoxy-2-phthalimido-
glucopyranoside (33)
b-D-
Prepared from 31 (245 mg, 0.21 mmol) according to general
method IV. Column chromatography of the residue (1:1 EtOAc–
23
hexane) gave compound 33 (170 mg, 70%) as a syrup: [a]
D
ꢀ21.9 (c 0.15, CHCl3). 1H NMR (360 MHz)
¼7.97 (d, 2H, J¼7.3 Hz,
d
4.25. Methyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-
arom.), 7.80 (dd, 2H, J¼5.2, 3.0 Hz, arom.), 7.68 (dd, 2H, J¼5.3,
3.0 Hz, arom.), 7.60 (t, 1H, J¼7.3 Hz, arom.), 7.49 (dd, 4H, J¼14.6,
7.3 Hz, arom.), 7.33–7.16 (m, 23H, arom.), 5.49 (s, 1H, PhCH), 5.21
(dd, 1H, J¼8.5, 2.5 Hz), 5.07 (s, 1H), 5.03 (dd, 1H, J¼10.3, 9.4 Hz),
4.92 (d, 1H, J¼8.5 Hz), 4.85 (d, 1H, J¼6.6 Hz), 4.82 (d, 1H,
J¼9.4 Hz), 4.73 (d, 1H, J¼12.5 Hz), 4.53–4.25 (m, 7H), 4.20 (s, 1H),
4.03–3.82 (m, 9H), 3.64–3.54 (m, 4H), 3.42 (s, 1H), 3.31 (s, 3H,
benzylidene-
-arabinopyranosyl)-2-deoxy-2-phthalimido-
glucopyranoside (31)
b-D-galactopyranosyl)-4-O-(2,3,4-tri-O-benzyl-b-
D
b-D-
To a solution of compound 30 (355 mg, 0.28 mmol) in CH2Cl2
(2 mL), MeOH (8 mL) and pyridine (2 mL) was added thiourea
(77 mg, 5 equiv) and the reaction stirred overnight. The mixture
was diluted with CH2Cl2, washed twice with water, dried (MgSO4)
and concentrated. Column chromatography of the residue (92:8
CH2Cl2–EtOAc) gave compound 31 (248 mg, 73%) as a syrup: [a]
D
OCH3) ppm. 13C NMR (90 MHz)
d
¼165.46 (PhC]O), 139.36,
139.17, 138.48, 138.08, 137.71, 134.21, 133.21, 131.49, 129.97,
129.41, 128.69, 128.49, 128.19, 128.10, 128.03, 127.83, 127.50,
127.36, 126.98, 126.75, 125.60, 123.29 (arom. Cs), 99.62, 98.93
(PhCH, C-1), 98.26 (C-100, J¼170.9 Hz), 96.21 (C-10, J¼164.4 Hz),
78.14, 76.12, 75.73, 75.50, 75.44, 73.47, 72.38, 71.14, 68.88, 65.90
(skeleton Cs), 74.80, 73.47, 71.54, 70.56 (4ꢃPhCH2), 69.25, 67.09
(C-6, C-60), 60.77 (C-500), 56.25, 56.16 (OCH3, C-2) ppm. Anal.
Calcd for C68H67O17N (1170.26): C, 69.79; H, 5.77; N, 1.20. Found:
C, 69.62; H, 5.83; N, 1.17. MALDI-TOF: m/z calcd for [MþNa]þ
1192.43. Found: 1192.66.
23
ꢀ21.4 (c 0.13, CHCl3). IR nmax (KBr) 3452, 3027, 2969, 2923, 1736,
1717, 1452, 1364, 1266, 1227, 1216, 1092, 1052, 1027, 997, 737, 713,
697, 528 cmꢀ1; 1H NMR (360 MHz)
d
¼7.86 (d, 2H, J¼7.8 Hz, arom.),
7.80–7.68 (m, 4H, arom.), 7.57 (t, 1H, J¼7.2 Hz, arom.), 7.48–7.40
(m, 4H, arom.), 7.36–7.14 (m, 23H, arom.), 5.49 (s, 1H, PhCH), 5.31
(t, 1H, J¼9 Hz), 5.15 (s, 1H), 4.99 (t, 1H, J¼9.9 Hz), 4.85 (d, 1H,
J¼11.4 Hz), 4.80 (d, 1H, J¼8.5 Hz), 4.71 (d, 1H, J¼12.6 Hz), 4.57–4.30
(m, 7H), 4.56 (t,1H, J¼9.6 Hz), 4.05–3.88 (m, 8H), 3.73–3.53 (m, 3H),
3.48–3.38 (m, 2H), 3.25 (s, 4H), 2.64 (br s, 1H, OH) ppm. 13C NMR
4.28. Methyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-
(90 MHz)
d
¼166.33 (PhC]O), 139.25, 139.04, 138.34, 138.02, 137.19,
benzylidene-b-D-gulopyranosyl)-4-O-(2,3,4-tri-O-benzyl-a-L-
134.22, 132.84, 131.25, 129.81, 129.55, 128.82, 128.39, 128.09, 128.01,
127.95, 127.75, 127.37, 127.19, 126.93, 126.84, 126.69, 125.47, 123.38
(arom. Cs), 99.92, 99.63, 98.66, 98.20 (PhCH, C-1, C-10, C-100), 78.03,
75.65, 75.50, 75.36 (double int.), 73.47, 73.30, 72.14, 71.55, 66.46
(skeleton Cs), 74.71, 72.82, 71.46, 70.50 (4ꢃPhCH2), 68.87, 67.02
(C-6, C-60), 60.61 (C-500), 56.00, 55.93 (OCH3, C-2) ppm. Anal. Calcd
for C68H67O17N (1170.26): C, 69.79; H, 5.77; N, 1.20. Found: C, 69.68;
H, 5.84; N, 1.18. MALDI-TOF: m/z calcd for [MþNa]þ 1192.43. Found:
1192.67.
fucopyranosyl)-2-deoxy-2-phthalimido-
(34)
b-D-glucopyranoside
Prepared from 32 (936 mg, 0.79 mmol) according to general
method IV. Column chromatography of the residue (1:1 EtOAc–
23
hexane) gave compound 34 (625 mg, 64%) as a syrup: [
a
]
D
ꢀ11
(c 0.25, CHCl3). IR nmax (KBr) 3410, 3062, 3030, 2922, 2853, 2357,
1777,1715,1496, 1452,1386,1361,1316,1270,1220,1135,1097,1044,
1027, 1015, 995, 754, 737, 722, 699 cmꢀ1 1H NMR (360 MHz)
;
d¼7.95 (d, 2H, J¼7.9 Hz, arom.), 7.83–7.76 (m, 2H, arom.), 7.69 (dd,
4.26. Methyl 6-O-benzyl-3-O-(2-O-benzoyl-4,6-O-
2H, J¼5.3 Hz, J¼3.1 Hz, arom.), 7.63–7.46 (m, 5H, arom.), 7.35–7.14
(m, 23H, arom.), 5.56 (s, 1H, PhCH), 5.26 (dd, 1H, J¼8.4, 2.1 Hz),
5.06–4.98 (m, 2H), 4.93–4.78 (m, 4H), 4.61–4.55 (m, 3H), 4.44–4.25
(m, 4H), 4.21 (s, 1H), 4.16 (d, 1H, J¼11.3 Hz), 4.06 (d, 1H, J¼11.3 Hz),
3.99–3.88 (m, 5H), 3.66–3.51 (m, 4H), 3.30 (s, 3H, OCH3), 3.22
(s, 1H), 1.88–1.70 (br s, 1H, OH), 1.23 (d, 3H, J¼6.9 Hz, CH3-600) ppm.
benzylidene-
-fucopyranosyl)-2-deoxy-2-phthalimido-
glucopyranoside (32)
b-D-galactopyranosyl)-4-O-(2,3,4-tri-O-benzyl-a-
L
b-D-
Prepared from 29 (104 mg, 0.08 mmol) in a similar manner as
described in Section 4.24. Column chromatography of the residue
(1:1 EtOAc–hexane) gave compound 32 (87 mg, 84%) as a syrup:
13C NMR (90 MHz)
d
¼165.32 (PhC]O), 139.46, 139.24, 138.40,
138.18, 137.73, 134.18, 133.23, 131.50, 129.98, 129.37, 128.68, 128.20,

Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
2413
128.09, 127.78, 127.44, 127.38, 127.26, 127.03, 126.83, 125.71, 123.32
(arom. Cs), 99.52, 98.90 (PhCH, C-1), 97.81 (C-100, J¼169.1 Hz), 96.39
(C-10, J¼161.3 Hz), 79.57, 78.81, 76.16, 75.56, 75.32, 72.98, 72.73,
71.07, 69.01, 66.29, 65.91 (skeleton Cs), 74.83, 74.67, 72.81, 71.14
(4ꢃPhCH2), 69.33, 67.04 (C-6, C-60), 56.15 (double int.)(OCH3, C-2),
16.49 (C-600) ppm. Anal. Calcd for C69H69O17N (1184.28): C, 69.98; H,
5.87; N, 1.18. Found: C, 69.90; H, 5.91; N, 1.16. MALDI-TOF: m/z calcd
for [MþNa]þ 1206.45. Found: 1206.76.
H-60a, PhCH2), 4.24–4.12 (m, 2H, H-2, PhCH2), 4.08–3.92 (m, 6H, H-
60b, H-200, H-40, H-4, H-300, H-6a), 3.83 (d, 1H, J¼10.7 Hz, H-30), 3.68–
3.44 (m, 4H, H-6b, H-5, PhCH2, H-50), 3.22 (s, 4H, H-400, OCH3), 1.99
(s, 3H, SCOCH3), 1.34 (d, 3H, J¼6 Hz, CH3-600) ppm. 13C NMR
(90 MHz)
d
¼194.00 (SCOCH3), 164.92 (PhC]O), 139.34, 139.08,
138.23, 138.10, 137.20, 134.05, 132.64, 131.13, 129.70, 129.45, 128.68,
128.50, 127.96, 127.61, 127.31, 127.24, 127.20, 127.02, 126.91, 126.65,
125.50, 123.39 (arom. Cs), 101.52 (C-10, J¼160 Hz), 99.74 (PhCH,
J¼161 Hz), 98.47 (C-1, J¼161.2 Hz), 97.72 (C-100, J¼170.8 Hz), 79.41
75.51, 75.37, 75.20, 73.03 (C-200, C-300, C-4, C-5, C-40), 78.79 (C-400),
74.66, 74.50, 72.66, 70.98 (4ꢃPhCH2), 73.97 (C-3), 68.87 (C-60),
68.71 (C-20), 68.14 (C-50), 66.90 (C-6), 66.14 (C-500), 55.72 (double
int.)(C-2, OCH3), 46.82 (C-30), 30.05 (SCOCH3), 16.04 (C-600) ppm.
Anal. Calcd for C71H71O17NS (1242.38): C, 68.64; H, 5.76; N, 1.13; S,
2.58. Found: C, 68.50; H, 5.80; N, 1.15; S, 2.60. MALDI-TOF: m/z calcd
for [MþNa]þ 1264.43. Found: 1264.71.
4.29. Methyl 3-O-(3-S-acetyl-2-O-benzoyl-4,6-O-benzylidene-
b
-
D
-galactopyranosyl)-6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-
-arabinopyranosyl)-2-deoxy-2-phthalimido-
glucopyranoside (35)
b-
D
b-D-
To a solution of compound 33 (205 mg, 0.18 mmol) in dry CH2Cl2
(2 mL) and pyridine (0.5 mL) in a CEM equipped vessel was added
dropwise Tf2O (67 m
L, 1.6 equiv) at 0 ꢁC and the mixture was
allowed to reach rt and stirred for half an hour. The mixture was
activated under MW conditions (t¼1 h, T¼35 ꢁC, power¼10 kW,
pressure¼20 PSI), then diluted with CH2Cl2, washed twice with
water, dried (MgSO4) and concentrated. The crude triflate was left
under high vacuum for 3 h. To a solution of the crude triflate in dry
DMF (6 mL) was added KSAc (62 mg, 3 equiv) and the reaction
stirred at 70 ꢁC for 2 h. The residue was diluted with EtOAc, washed
three times with water, dried (MgSO4) and concentrated. Column
4.31. Methyl 3-O-(2-O-benzoyl-4,6-O-benzylidene-3-deoxy-3-
sodiumsulfonato-
(2,3,4-tri-O-benzyl-
phthalimido- -glucopyranoside (37)
b-D
-galactopyranosyl)-6-O-benzyl-4-O-
b-D-arabinopyranosyl)-2-deoxy-2-
b-D
Prepared from 35 (117 mg, 0.10 mmol) in a similar manner as
described in Section 4.8. Column chromatography of the residue
(92:8 CH2Cl2–MeOH) gave compound 37 (67 mg, 56%) as a syrup
23
chromatography (1:1 EtOAc–hexane) of the residue gave com-
and 35 (22 mg, 18%) was also recovered. Compound 37: [
a]
ꢀ15.1
D
23
pound 35 (150 mg, 70%) as a syrup: [
a
]
D
ꢀ4.2 (c 0.02, CHCl3). IR
(c 0.11, CHCl3, one drop of MeOH). IR nmax (KBr) 3452, 2969, 1734,
1716, 1452, 1365, 1228, 1216, 1091, 689, 527 cmꢀ1 1H NMR
(360 MHz, CDCl3, CD3OD)
nmax (KBr) 3457, 2969, 1736, 1453, 1365, 1228, 1216, 1091, 696,
527 cmꢀ1 1H NMR (360 MHz)
¼7.82–7.69 (m, 5H, arom.), 7.60 (t,
;
;
d
d
¼7.90–7.15 (m, 34H), 5.64 (s, 1H, PhCH),
1H, J¼7.3 Hz, arom.), 7.49–7.39 (m, 4H, arom.), 7.36–7.17 (m, 24H,
arom.), 5.52 (s, 1H, PhCH), 5.34 (dd, 1H, J¼10.5, 8.1 Hz, H-20), 5.14
(d, 1H, J¼2.5 Hz, H-100), 4.93 (t, 1H, J¼9.9 Hz, H-3), 4.84 (d, 1H,
J¼11.9 Hz, PhCH2), 4.81 (d,1H, J¼9.1 Hz, H-1), 4.69 (d,1H, J¼12.7 Hz,
C-500a), 4.57–4.37 (m, 7H, H-10, H-60a, PhCH2), 4.18 (dd, 1H, J¼10.3,
8.8 Hz, H-2), 4.03–3.88 (m, 7H, H-200, H-300, H-40, H-4, H-6a, H-60b,
PhCH2), 3.85–3.77 (m, 2H, H-30, PhCH2), 3.70–3.49 (m, 4H, H-500b,
H-6b, H-5, H-50), 3.40 (s, 1H, H-400), 3.25 (s, 3H, OCH3), 2.05 (s, 3H,
5.09 (s, 1H), 4.94 (t, 1H, J¼9.3 Hz), 4.88–4.74 (m, 3H), 4.63–4.29 (m,
11H), 4.18 (d, 1H, J¼12.2 Hz), 4.10–4.00 (m, 2H), 3.96–3.81 (m, 3H),
3.71 (d, 1H, J¼11.6 Hz), 3.68–3.54 (m, 3H), 3.43–3.33 (m, 2H), 3.27
(s, 3H, OCH3) ppm. 13C NMR (90 MHz)
d
¼166.68 (PhC]O), 138.72,
138.55, 137.82, 137.59, 134.07, 132.39, 130.88, 129.90, 129.27, 128.17,
127.83, 127.62, 127.54, 127.29, 127.14, 127.01, 126.83, 126.67, 125.64,
123.33 (arom. Cs), 99.65, 98.56, 98.31 (C-1, C-10, C-100), 77.75, 75.21,
75.10, 74.96, 74.16, 73.52, 72.84, 68.37 (skeleton Cs), 74.43, 72.72,
71.50, 70.60 (4ꢃPhCH2), 68.87 (C-60), 66.93 (C-6), 60.92 (C-500),
56.00, 55.80 (C-2, OCH3) ppm. MALDI-TOF m/z calcd for
C68H66O19NSNa (1256.30), [MþNa]þ 1278.37. Found: 1278.59.
SCOCH3) ppm. 13C NMR (90 MHz)
d
¼194.48 (SCOCH3), 165.14
(PhC]O), 139.42, 139.27, 138.49, 138.20, 137.29, 134.17, 132.83,
131.39, 129.90, 129.60, 128.84, 128.58, 128.18, 128.10, 128.05, 127.83,
127.50, 127.42, 127.29, 126.98, 126.73, 125.56, 123.58 (arom. Cs),
101.51 (C-10, J¼160.4 Hz), 100.09 (C-1, J¼161 Hz), 98.65 (PhCH,
J¼162.6 Hz), 98.27 (C-100, J¼173.1 Hz), 78.09, 75.74, 75.62, 75.59
(double int.), 75.53, 68.38 (skeleton Cs), 74.86, 72.93, 71.51, 70.55
(4ꢃPhCH2), 69.01 (C-60), 67.11 (C-1), 60.55 (C-500), 56.00, 55.90 (C-2,
OCH3), 46.95 (C-30), 30.28 (SCOCH3) ppm. Anal. Calcd for
C70H69O17NS (1228.36): C, 68.44; H, 5.66; N, 1.14; S, 2.61. Found: C,
68.32; H, 5.70; N, 1.15; S, 2.59. MALDI-TOF: m/z calcd for [MþNa]þ
1250.42. Found: 1250.62.
4.32. Methyl 2-acetamido-6-O-benzyl-4-O-(2,3,4-tri-O-
benzyl-
deoxy-3-sodiumsulfonato-
-glucopyranoside (38)
b
-
D
-arabinopyranosyl)-3-O-(4,6-O-benzylidene-3-
b-D
-galactopyranosyl)-2-deoxy-b-
D
To a solution of compound 37 (43 mg, 0.03 mmol) in anhyd
ethanol (5 mL) was added EDA (300 L) and the reaction heated at
m
reflux for two days. The amine was detected by ninhydrin and the
mixture was concentrated and coevaporated twice with toluene.
The residue was dissolved in MeOH (3 mL) and treated with Ac2O
(1 mL). After 1 h the mixture was concentrated and coevaporated
4.30. Methyl 3-O-(3-S-acetyl-2-O-benzoyl-4,6-O-benzylidene-
b-D-galactopyranosyl)-6-O-benzyl-4-O-(2,3,4-tri-O-benzyl-a-L-
fucopyranosyl)-2-deoxy-2-phthalimido-
(36)
b
-D-glucopyranoside
twice with toluene. Column chromatography of the residue (85:15
CH2Cl2–MeOH) gave compound 38 (39 mg, 64%) as a syrup: [a]
D
23
ꢀ67.2 (c 0.1, MeOH). IR nmax (KBr) 3415, 2922, 1649, 1555, 1496,
Prepared from 34 (623 mg, 0.53 mmol) in a similar manner as
described in Section 4.29. Column chromatography of the residue
(1:1 EtOAc–hexane) gave compound 36 (507 mg, 78%) as a syrup:
1452, 1365, 1188, 1138, 1091, 1054, 1028, 1000, 736, 696, 645, 573,
523 cmꢀ1
;
1H NMR (360 MHz, CDCl3, CD3OD)
d
¼7.64 (d, 2H,
J¼7.6 Hz, arom.), 7.40–7.11 (m, 23H, arom.), 5.67 (s, 1H, PhCH), 5.03
(s, 1H), 4.65–4.40 (m, 6H), 4.38–4.11 (m, 6H), 4.04–3.25 (m, 19H),
3.17 (d, 1H, J¼9.4 Hz), 2.03 (s, 3H, NHCOCH3) ppm. 13C NMR
23
[
a]
þ3.1 (c 0.16, CHCl3). IR nmax (KBr) 3477, 3061, 3029, 2902,
D
2864, 2358, 1778, 1715, 1602, 1584, 1495, 1467, 1452, 1386, 1362,
1318, 1261, 1213, 1163, 1135, 1095, 1055, 1027, 1000, 952, 932, 910,
(90 MHz)
d¼172.64 (NHCOCH3), 138.50, 138.28, 137.84, 137.59,
793, 734, 722, 711, 697, 630, 530 cmꢀ1; 1H NMR (360 MHz)
d
¼7.77–
137.28, 127.76, 127.56, 127.48, 127.33, 127.19, 127.05, 126.96, 126.74,
126.46, 126.30, 125.39 (arom. Cs), 103.17, 100.84, 99.15, 97.72 (PhCH,
C-1, C-10, C-100), 77.11, 76.38, 74.97, 74.85, 74.40, 72.78 (double int.),
68.06, 66.42, 62.03 (skeleton Cs), 74.20, 72.48, 71.03, 69.96
(4ꢃPhCH2), 68.66 (C-60), 66.77 (C-6), 60.35 (C-500), 55.62, 55.18
7.66 (m, 5H, arom.), 7.60–7.52 (m, 4H, arom.), 7.43–7.15 (m, 25H,
arom.), 5.54 (s, 1H, PhCH), 5.36 (dd, 1H, J¼10.1 Hz, J¼8.2 Hz, H-20),
5.10 (s, 1H, H-100), 4.97–4.79 (m, 4H, H-3, H-500, H-1, PhCH2), 4.71–
4.59 (m, 3H, PhCH2), 4.50 (d, 1H, J¼7.1 Hz, H-10), 4.46–4.36 (m, 3H,

2414
Z. Jakab et al. / Tetrahedron 66 (2010) 2404–2414
(OCH3, C-2), 21.81 (NHCOCH3) ppm. MALDI-TOF m/z calcd for
C55H62O17NSNa (1064.13), [MþNa]þ 1086.35. Found: 1086.50.
residue (5:4:1 CH2Cl2–MeOH–water) gave 4 (36 mg, 92%) as an
23
amorphous powder: [
a
]
ꢀ58.4 (c 0.11, MeOH). IR nmax (KBr) 3420,
D
2932,1651,1557,1377,1318,1168,1037, 965, 809, 772, 635, 523 cmꢀ1
;
4.33. Methyl 2-acetamido-6-O-benzyl-4-O-(2,3,4-tri-O-
1H NMR (360 MHz, CD3OD)
d
¼5.04 (d,1H, J¼3.8 Hz, H-100), 4.89–4.82
benzyl-
sodiumsulfonato-
glucopyranoside (39)
a
-
L
-fucopyranosyl)-3-O-(4,6-O-benzylidene-3-deoxy-3-
(m,1H, H-500), 4.54 (d,1H, J¼7.4 Hz, H-10), 4.37 (d,1H, J¼8.2 Hz, H-1),
4.22 (d, 1H, J¼1.8 Hz, H-40), 4.02–3.68 (m, 11H, H-2, H-20, H-200, H-3,
H-300, H-4, H-400, H-6a, H-6b, H-60a, H-60b), 3.54–3.48 (m, 1H, H-50),
3.46 (s, 3H, OCH3), 3.44–3.37 (m, 1H, H-5), 2.85 (dd, 1H, J¼10.8,
2.3 Hz, H-30), 1.98 (s, 3H, NHCOCH3), 1.17 (d, 3H, J¼6.5 Hz, CH3-600)
b-
D
-galactopyranosyl)-2-deoxy-
b-D-
To a solution of compound 36 (157 mg, 0.13 mmol) in anhyd
ethanol (5 mL) was added EDA (1 mL) and the reaction heated at
reflux for one day. The amine was detected by ninhydrin and the
mixture was concentrated and coevaporated twice with toluene.
The residue was dissolved in MeOH (3 mL) and treated with Ac2O
(1 mL). After 1 h the mixture was concentrated, coevaporated twice
with toluene and dried. The residue was oxidized in a similar
manner as described in Section 4.8. Column chromatography of the
ppm.13C NMR (90 MHz, CD3OD)
d
¼174.18 (NHCOCH3),105.21 (C-100),
103.34 (C-10), 99.73 (C-1), 78.90, 78.27, 77.39, 73.72 (double int.),
71.69, 70.20, 68.22, 67.71, 66.93 (skeleton Cs), 64.86 (C-30), 62.45
(C-60), 61.25 (C-6), 57.15, 57.03 (OCH3, C-2), 23.24 (NHCOCH3), 16.74
(C-600) ppm. MALDI-TOF m/z calcd for C21H36O17NSNa (629.56),
[MþNa]þ 652.15. Found: 652.21.
residue (8:2 CH2Cl2–MeOH) gave compound 39 (93 mg, 62% over
Acknowledgements
23
three steps) as a syrup: [
(360 MHz, CDCl3, CD3OD)
a
]
ꢀ57.7 (c 0.15, MeOH). 1H NMR
D
d
¼7.71 (d, 2H, J¼7.3 Hz, arom.), 7.40–7.13
This work was supported by the Hungarian National Fund
(NK48798 to A.L., PD73064 to A.F., K62802 to A.B. and NI61336 to
S.A.). We thank to Sz. Fekete for reactions with the CEM Discover
(m, 23H, arom.), 5.70 (s, 1H, PhCH), 4.98 (d, 1H, J¼2.3 Hz), 4.90 (dd,
1H, J¼12.8, 6.5 Hz), 4.82–4.50 (m, 10H), 4.45 (d, 1H, J¼12.2 Hz),
4.37–4.06 (m, 5H), 4.01–3.75 (m, 5H), 3.63 (d, 1H, J¼10.4 Hz), 3.50
(s, 1H), 3.49–3.39 (m, 4H), 3.36–3.32 (m, 1H), 3.22 (s, 1H), 3.15
(dd, 1H, J¼10.8, 2.4 Hz), 2.03 (s, 3H, NHCOCH3), 1.11 (d, 3H, J¼6.3 Hz,
´
´
´
MW equipment (Peter Pazmany Program, NKTH, RET 006/2004).
References and notes
CH3-600) ppm. 13C NMR (90 MHz)
d¼174.07 (NHCOCH3), 139.89,
139.77, 139.09, 138.85, 138.58, 129.24, 128.87, 128.52, 128.31, 128.15,
127.91, 127.68, 126.88 (arom. Cs), 104.65, 102.27, 100.45 (PhCH, C-1,
C-10), 98.64 (C-100, J¼170.7 Hz), 79.88, 79.30, 76.04, 75.80, 74.19,
73.57, 69.42, 67.63, 67.40, 63.43 (skeleton Cs), 75.68, 75.47, 73.86,
71.90 (4ꢃPhCH2), 70.01 (C-60), 68.08 (C-6), 57.04, 56.28 (OCH3, C-2),
23.15 (NHCOCH3), 16.47 (C-600) ppm. MALDI-TOF m/z calcd for
C56H64O17NSNa (1078.16), [MþNa]þ 1100.37. Found: 1100.36.
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23
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D
3415, 2925, 1650, 1562, 1377, 1322, 1217, 1138, 1058, 840, 790, 632,
506 cmꢀ1 1H NMR (360 MHz, CD3OD)
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d
¼104.52, 102.82, 99.85 (C-1, C-10, C-100), 78.26, 76.94,
76.56, 73.99, 70.31, 69.55, 69.26, 67.91, 67.15, 64.98 (skeleton Cs),
64.80, 62.40, 60.86 (C-6, C-60, C-500), 57.91, 56.62 (OCH3, C-2), 23.32
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b-
D
-galactopyranosyl)-4-O-(
a-L-fucopyranosyl)-2-deoxy-b-D-
glucopyranoside (4)
To a solution of compound 39 (66 mg, 0.06 mmol) in ethanol
(5 mL) was added 10% Pd/C (30 mg) and the reaction stirred under
H2 (10 bar) for four days. The mixturewas filtered through Celite and
the filtrate was concentrated. Column chromatography of the
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´
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