Investigation of glycosylating properties of 1-deoxy-1-ethoxysulfonyl-hept- 2-ulopyranosyl derivatives. Synthesis of a new sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide

Article abstract of DOI:10.1016/j.carres.2011.04.027

Glycosylation reactions of the ethylthio, bromo and chloro derivatives of 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranose were studied applying different acceptors under different conditions. Elimination side-reactions affording exo- and endoglycals occured in all cases, however, with different proportions. Glycosyl chloride donor was applied to glycosylate a trisaccharide acceptor obtaining a new sulfonic acid mimetic of the sialyl Lewis X tetrasaccharide in high yield.

Full text of DOI:10.1016/j.carres.2011.04.027

Carbohydrate Research 346 (2011) 1527–1533
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Investigation of glycosylating properties of 1-deoxy-1-ethoxysulfonyl-
hept-2-ulopyranosyl derivatives. Synthesis of a new sulfonic acid mimetic
of the sialyl Lewis X tetrasaccharide
Magdolna Csávás a, Gábor Májer a, Mihály Herczeg a, Judit Remenyik b, László Lázár a,
a,c
Attila Mándi c, Anikó Borbás a, , Sándor Antus
⇑
a Research Group for Carbohydrates of the Hungarian Academy of Sciences, PO Box 94, Debrecen H-4010, Hungary
b Department of Plant Biotechnology, Central of Agricultural and Applied Economic Sciences, PO Box 36, Debrecen H-4015, Hungary
c Department of Organic Chemistry, PO Box 20, Faculty of Science, University of Debrecen, Debrecen H-4010, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Glycosylation reactions of the ethylthio, bromo and chloro derivatives of 1-deoxy-1-ethoxysulfonyl-hept-
2-ulopyranose were studied applying different acceptors under different conditions. Elimination side-
reactions affording exo- and endoglycals occured in all cases, however, with different proportions. Glyco-
syl chloride donor was applied to glycosylate a trisaccharide acceptor obtaining a new sulfonic acid
mimetic of the sialyl Lewis X tetrasaccharide in high yield.
Received 3 February 2011
Received in revised form 12 April 2011
Accepted 18 April 2011
Available online 24 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Dedicated to Professor András Lipták on the
occasion of his 75th birthday
Keywords:
Carbohydrate sulfonic acid
Glycosylation
Ketopyranosyl glycosides
Elimination
Sialyl Lewis X mimetic
1. Introduction
anomeric sulfonomethyl-type sugar moiety.7,8 To install the
sulfonomethyl derivative to oligosaccharides ethyl 3,4,5,7-tetra-
Selectins are carbohydrate-binding transmembrane glycopro-
teins, and their role is to mediate the first steps of the recruitment
of leukocytes from the blood stream in a series of normal and path-
ologic situations.1 Control of these processes by inhibiting the
adhesion between the calcium-dependent lectin domain of selec-
tins and their carbohydrate ligands has been considered as a new
anti-inflammatory and anti-metastatic strategy.2 Sialyl Lewis X
(sLex) tetrasaccharide, one of the major natural ligands of selectins
serves as a lead-structure for the design of selectin antagonists
(Fig. 1).3 The negatively charged carboxylate of sialic acid is crucial
in binding to transmembrane proteins, but it can be replaced by
other charged moieties. Analogues containing for example, sulfate
ester,4 phosphate ester5 or cyclohexyl lactic acid6 instead of sialic
acid proved to be active as selectin antagonists.
O-benzyl-1-deoxy-1-ethoxysulfonyl-2-thio-a-D-gluco-hept-2-ulo-
pyranoside was used as glycosyl donor. However, the yields of gly-
cosylation reactions were moderate since a considerable amount of
exo-glycal was always formed via elimination side-reaction.
Recently, two isosteric sulfonate mimetics of mannose-6-O-
phosphate prepared by Wadsworth–Horner–Emmons olefination
have been published.9 Both conjugated and unconjugated
mannose-sulfonates displayed better binding affinity to
cation-independent mannose-6-phosphate receptor and possessed
greater stability in human serum than mannose-6-phosphate.
-
OH
COO
OH
O
OH
HO
AcHN
OH
HO
OH
O
Earlier, we described the synthesis of sulfonic acid analogues of
the sLe X tetrasaccharide in which the sialic acid is replaced by an
O
O
O
OH
O
OH
NHAc
O
H3C
OH
OH
⇑
Corresponding author. Tel.: +36 52512900/22462; fax: +36 52512900/22342.
E-mail addresses: borbas.aniko@science.unideb.hu, borbasa@puma.unideb.hu
OH
(A. Borbás).
Figure 1. Structure of the sialyl Lewis X tetrasaccharide.
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.04.027

1528
M. Csávás et al. / Carbohydrate Research 346 (2011) 1527–1533
We have found that sulfonate analogues of idraparinux, a syn-
OBn
O
OBn
O
SO3Et
thetic non-glycosaminoglycan anticoagulant pentasaccharide
inhibited efficiently the blood coagulation factor Xa in an in vitro
assay.10
The experimental evidence of biological activity of carbohy-
drate sulfonic acids inspired us to revisit the synthesis of sulfonic
acid mimetic of sialic acid-containing oligosaccharides using ano-
meric sulfonomethyl-type donors.
BnO
BnO
BnO
BnO
OCH3
SO3Et
+
BnO
5
BnO
6
OCH3
2,3 or 4
OBn
OBn
SO3Et
O
BnO
BnO
O
SO3Et
BnO
BnO
Here, we report glycosylation reactions of ethylthio, chloro and
bromo derivatives of 3,4,5,7-tetra-O-benzyl-1-deoxy-1-eth-
+
OBn
7
OBn
oxysulfonyl-
a-
D-gluco-hept-2-ulopyranose
applying
different
8
acceptors and conditions. Efficient synthesis of a new sulfonic acid
tetrasaccharide analogue of the sialyl Lewis X is also discussed.
0
Scheme 2. Reagents and conditions: (i) MeOH (15 equiv), 3 ÅA MS, for solvents and
promoters see Table 1.
2. Results and discussion
2.1. Glycosylation study
Hg(II) salt instead of Ag(I) salt. Carrying out glycosylation with do-
nor 4 of low reactivity using less powerful activation the glycoside
formation decreased dramatically and elimination reactions be-
came the dominant reactions (entry 7).
Glycosylation reactions using acceptor 12 and 13 (Scheme 4)
are summarized in Tables 3 and 4. The main features of these reac-
tions were that elimination reactions generally overtook glycoside
Thioglycoside 2,7,8 and the appropriate bromo (3) and chloro (4)
derivatives were planned to be utilized as glycosyl donors. Com-
pound 2 was treated with bromine to produce 3; the reaction went
to completion in 10 min. The chlorosugar 4 was prepared from the
hemiketal 1 using thionyl chloride and pyridine as reagents
(Scheme 1).
The obtained 2–4 were used as donors to glycosylate MeOH
(Scheme 2), acceptor 911 containing free hydroxyl group at primary
position (Scheme 3) and acceptors 1211 and 1312 with secondary
alcoholic functions (Scheme 4), respectively. NIS–TfOH promoter
system was applied at different temperatures to activate the thio-
glycoside and MeOTf was also used as a promoter for glycosylation
of 12 and 13.13 Halide donors, prepared freshly before glycosyla-
tions and used without purification, were activated with either
AgOTf or Hg(CN)2 and chloro sugar was promoted also with a mix-
ture of Hg(CN)2 and HgBr2. Relative proportions of the products
were determined from the crude reaction mixture by HPLC
measurements.
formation and the a-linked disaccharides formed exclusively. Con-
figuration of the interglycosidic linkages of 14 and 15 was deter-
mined on the basis of the NMR C1–H3 three-bond coupling
constant which is dependent on the dihedral angle in a manner
3
13
similar to JH,H
.
Thioglycoside 2 upon powerful activation using NIS–TfOH was
inefficient for glycosylation of the unreactive acceptors 12 and
13; reactivity of the secondary hydroxyl groups was low at the
low temperature of activation (ꢀ40 °C), therefore, oxocarbenium
intermediate formed rapidly from the donor was stabilized via
elimination (Table 3: entries 1, 2 and Table 4: entry 1). Slow acti-
vation process of 2 at room temperature using the mild MeOTf as
a promoter gave slightly better results, due to the increasing reac-
tivity of the acceptor at higher temperature (Table 3: entry 3 and
Table 4: entry 2). Beside exo-glycal 7, formation of endoglycal 8
from thioglycoside was also observed.
The glycosylation results using MeOH as an acceptor (Scheme 2)
are summarized in Table 1. Each reaction afforded an anomeric
mixture of the methyl glycosides 5 and 6.13 Using the thioglycoside
donor 2 the stereoselectivity was poor in favour of either the
the b-anomer depending on the reaction temperature. Reactions
applying halide donors 3 and 4 provided the -isomer 5 as the ma-
Glycosyl halides proved to be more efficient donors for both
acceptors 12 and 13 than the thioglycoside. Interestingly, the out-
come of the reactions was greatly influenced by the aglycons of the
a- or
a
acceptors (a-methyl for 12 and b-p-methoxyphenyl for 13). For
jor product with high stereoselectivity. From the chloro and bro-
mo-sugars the known elimination side-product 77,8 was formed
in all cases, and upon AgOTf promotion the endoglycal 8 as another
side-product was observed as well.
Glycosylation reactions using acceptor 9 possessing a reactive
primary hydroxyl (Scheme 3) are summarized in Table 2. In each
case a mixture of the stereoisomeric 2,6-linked disaccharides 10
and 1111 together with elimination side-product(s) was formed.
Reactions using thioglycoside gave the disaccharides with the
acceptor 12 the more reactive halide donor 3 with the less power-
ful promoter Hg(CN)2 worked as well than the less reactive halide
donor 4 with the more powerful promoter AgOTf (Table 3: entries
5 and 6). For acceptor 13 chlorosugar 4 upon AgOTf promotion
worked much better than bromosugar 3 activated by Hg(CN)2
(Table 4: entries 5 and 4).
Summarising the results, using ketosyl donors carrying a sulfo-
nomethyl moiety at the anomeric position the outcome of glyco-
sylation reactions strongly depends on the reactivity of the
acceptor. The oxocarbenium ion formed upon activation can react
with the aglycon to form glycoside, or can transform easily to gly-
cal derivatives via elimination of the labile proton next to the elec-
tron withdrawing sulfonic acid moiety. The ratio of glycosylation
highest proportion and the highest a-selectivity; by using chloro-
and bromo sugars upon AgOTf promotion at ꢀ15 °C a slightly low-
er rate of disaccharides and lower stereoselectivity were achieved.
For both halide donors the rate of glycosylation decreased using
OBn
OBn
OBn
O
SO3Et
SO3Et
SO3Et
O
iii
BnO
BnO
i
O
BnO
BnO
BnO
BnO
BnO
BnO
BnO
R
Cl
OH
2
4
R= SEt
1
ii
3 R= Br
Scheme 1. Reagents and conditions: (i) EtSH, BF3ꢁEt2O, abs CH2Cl2, 0 °C, 93%; (ii) Br2, abs CH2Cl2, 0 °C, 10 min; (iii) SOCl2, py, abs CH2Cl2, rt, 10 min, 85%.

M. Csávás et al. / Carbohydrate Research 346 (2011) 1527–1533
1529
OBn
SO3Et
O
OBn
O
BnO
BnO
OH
BnO
BnO
O
BnO
O
2 3
,
4
or
BnO
BnO
O
O
+
BnO
BnO
7
8
+
O
+
BnO
BnO
BnO
BnO
EtO3S
BnO
OCH3
BnO
OCH3
OCH3
9
10
11
Scheme 3. Reagents and conditions: see Table 2.
Table 3
OBn
SO3Et
OBn
Glycosylation of 12 with 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranosyl donors
O
OBn
O
BnO
Entry Donor Promotera
T (°C) Time 14 (%) 7 (%) 8 (%)
BnO
2 3
,
4
or
HO
BnO
R1
+
BnO
7 8
+
O
R1
1
2
3
4
5
6
7
2
2
2
3
3
4
4
NIS–TfOH
NIS–TfOH
MeOTf
AgOTf
Hg(CN)2
AgOTf
ꢀ40
0
30 min 17.4
55.1
99.4b
76.8b
40.8
35.0
45.2
62.0
27.5
O
BnO
BnO
R2
2 h
0.6
23.2
28.6
39.6
40.0
11.2
BnO
R2
rt
0
0
0
0
1 day
1 h
1 h
1 h
4 days
R1 = H, R2 = OCH3
R1 = OPMP, R2 = H
12
13
14
15
30.6
25.4
14.8
26.8
Scheme 4. Reagents and conditions: see Tables 3 and 4.
Hg(CN)2–HgBr2
a
Amount of promoters: NIS (1.2 equiv) TfOH (0.4 equiv); MeOTf (6 equiv); AgOTf
(2 equiv); Hg(CN)2 (1 equiv); Hg(CN)2–HgBr2 (1.5–0.5 equiv).
Ratio of 7 and 8 was not determined. Solvents: CH2Cl2 for entries 1–3, CH2Cl2–
toluene for entries 4 and 6, CH2Cl2–CH3CN for entries 5 and 7.
Table 1
Glycosylation of MeOH with 1-deoxy-1-ethloxysulfonyl-hept-2-ulopyranosyl donors
b
Entry Donor Promotera
T (°C)
Time
5
6
7
8
(%)
(%)
(%)
(%)
1
2
3
4
2
2
2
3
NIS–TfOH
NIS–TfOH
NIS–TfOH
AgOTf
ꢀ60
0
rt
ꢀ40 to
ꢀ10
0
ꢀ40 to
ꢀ10
0–rt
40 min 43
40 min 62
30 min 69
57
38
31
—
—
—
0.7
—
—
—
0.4
Table 4
Glycosylation of 13 with 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranosyl donors
Entry Donor Promotera
T (°C) Time
15 (%) 7 (%) 8 (%)
20 min 81.3 17.6
1
2
3
4
5
6
2
2
3
3
4
4
NIS–TfOH
MeOTf
AgOTf
Hg(CN)2
AgOTf
Hg(CN)2–HgBr2
ꢀ40
rt
0
65 min 12.0
1 day
2 h
86.1
81.5b
30.5
29.3
29.1
50.7
1.9
5
6
3
4
Hg(CN)2
AgOTf
20 min 65.2 33.1
5 h 80.7 12.0
1.6
5.4
—
1.9
18.5
13.5
16.2
63.4
16.3
56.0
54.5
7.5
0
0
0
2.5 h
2 days
5 days
7
4
Hg(CN)2–
HgBr2
5 h 84.9
9.5
5.6
—
33.0
a
Amount of promoters: NIS (1.2 equiv) TfOH (0.4 equiv); Hg(CN)2 (1 equiv);
a
Amount of promoters: NIS (1.2 equiv) TfOH (0.4 equiv); MeOTf (6 equiv); AgOTf
(2 equiv); Hg(CN)2 (1 equiv); Hg(CN)2–HgBr2 (1.5–0.5 equiv).
AgOTf (2 equiv); Hg(CN)2–HgBr2 (1.5–0.5 equiv). Solvents: CH2Cl2 for entries 1–3,
CH2Cl2–toluene for entries 4 and 6, CH2Cl2–CH3CN for entries 5 and 7.
b
Ratio of 7 and 8 was not determined. Solvents: CH2Cl2 for entries 1 and 2,
CH2Cl2–toluene for entries 3 and 5, CH2Cl2–CH3CN for entries 4 and 6.
Table 2
Glycosylation of 9 with 1-deoxy-1-ethoxysulfonyl-hept-2-ulopyranosyl donors
Acceptors with low reactivity could not be glycosylated at low
temperature, therefore, application of reactive donors and promot-
ers should be avoided. Increasing the temperature both glycosyla-
tion and elimination became faster, and an optimum of their
relative rates can lead to better results. In our case, the chlorosugar
with the lowest reactivity proved to be the best donor to glycosy-
late 12 and 13.
Entry Donor Promotera
T
(°C)
Time
10
(%)
11
(%)
7
(%)
8
(%)
1
2
3
4
5
6
2
2
3
3
4
4
NIS–TfOH
NIS–TfOH
AgOTf
Hg(CN)2
AgOTf
ꢀ50
ꢀ5
ꢀ15
0
1 h
81.6
6.7
11.7
—
0
30 min 74.4
7.5 h
3 h
8 h
18 h
7.7
24.0
19.4
6.3
17.9
63.6
55.2
71.5
55.8
12.4b
25.4b
19.8
ꢀ15
2.4
Hg(CN)2–
HgBr2
0
19.6
24.6b
2.2. Synthesis of a new sialyl Lewis X mimic
7
4
Hg(CN)2
rt
18 h
11.3
8.5
57.1 23.1
a
Amount of promoters: NIS (1.2 equiv) TfOH (0.4 equiv); Hg(CN)2 (1 equiv);
Synthesis of tetrasaccharide 21 as a new sulfonic acid analogue
of the sialyl Lewis X was carried out as shown in Scheme 5. It is
known from SAR study of the sLex tetrasaccharide analogues, that
2-acetamido group of its glucosamine residue is not involved in
binding to selectins, therefore, the cheap and easily available lac-
tose could be used for the synthesis instead of lactosamine. The
30,40-O-isopropylidene derivative of p-methoxyphenyl lactoside
1614 was converted to crystalline 17 in high yield by the well-
established selective benzoylation.15 Fucosylation of acceptor 17
AgOTf (2 equiv); Hg(CN)2–HgBr2 (1.5–0.5 equiv).
Ratio of 7 and 8 was not determined. Solvents: CH2Cl2 for entries 1 and 2,
CH2Cl2–toluene for entries 3 and 5, CH2Cl2–CH3CN for entries 4, 6 and 7.
b
and elimination is determined by the relative rate of formation of
the oxocarbenium cation, its reaction with the acceptor and the
elimination reaction from the oxocarbenium intermediate.
During glycosylation of MeOH, the elimination was negligible,
independently of the applied donor or promoter, due to the imme-
diate reaction of the oxocarbenium ion with the highly reactive
alcohol. In the reactions of acceptor 9 containing a primary hydro-
xyl, at lower temperature glycoside formation was more favoured.
Accordingly, more reactive donor afforded better results.
with ethyl 2,3,4-tri-O-benzyl-1-thio-b-L
-fucoside 1816 upon
TMSOTf activation afforded the Lewis X mimetic 19. Deisopropyli-
denation of the fully protected trisaccharide using methanolic
HCl17 gave 20 without affecting the highly acid sensitive
a-fucosi-
dic linkage. Then the diol was glycosylated with both thioglycoside

1530
M. Csávás et al. / Carbohydrate Research 346 (2011) 1527–1533
anolic sulfuric acid soln followed by heating. Column chromatogra-
phy was performed on Silica Gel 60 (Merck 0.063–0.200 mm) and
Sephadex LH-20 (Sigma–Aldrich, Bead size 25–100 ). Organic
O
OR
O
OR
O
O
OPMP
O
l
HO
OR
16 R = H
OR
solutions were dried over MgSO4 and concentrated in vacuum.
The 1H (200, 360, 400 and 500 MHz) and 13C NMR (50.3, 90.54,
100.28, 125.76 MHz) spectra were recorded with Bruker AC-200,
Bruker DRX-360, Bruker DRX-400 and Bruker DRX-500 spectrome-
ters. Chemical shifts are referenced to Me4Si (0.00 ppm for 1H) or to
the residual solvent signals (CDCl3: 77.00 ppm for 13C). MALDI-TOF
MS analyses of the compounds were carried out in the positive
reflectron mode using a BIFLEX III mass spectrometer (Bruker, Ger-
many) equipped with delayed-ion extraction. The matrix solution
was a satd 2,4,6-trihydroxy-acetophenone (THAP) solution in
MeCN. A Hewlett–Packard 1090 series II Liquid Chromatograph
equipped with a diode array detector (DAD), an automatic samples
and Chem Station were used for the separation experiments. The
i
17
R = Bz
SEt
O
ii
OBn
OBn
18
BnO
R2O
R1O
OBz
OBz
O
O
O
OPMP
O
OBz
OBz
O
OBn
OBn
BnO
iii
separation was performed using a Supelcosil Si 5 lm column. n-
19 R1, R2 = (CH3)2C
Hexane–ethyl-acetate mixture was used as eluent. The effluent
was monitored for UV-active groups at 256 nm. The component ra-
tio was given on the basis of the Area% of the HPLC analysis.
R
= R2 = H
1
20
iv
2
4
or
3.2. General method A for glycosylation of MeOH starting from
thioglycoside 2
SO3Et
OH
OBn
O
To a solution of 1 mmol thioglycoside donor (1 equiv) in dry
CH2Cl2 (15 mL) 3 Å molecular sieves and MeOH (15 equiv) were
added and it was stirred for 3 h. The reaction mixture was cooled
to the appropriate temperature then the solution of NIS (1.2 equiv)
and TfOH (0.4 equiv) in dry CH2Cl2 and THF (1:1, 2 mL) was added.
When TLC showed complete conversion of the donor, the reaction
mixture was quenched with Et3N, the insoluble materials were re-
moved by filtration, the filtrate was diluted with CH2Cl2 and
washed with water, filtered, dried and concentrated. The ratio of
the products was determined from the crude product by HPLC.
OBz
O
OBz
O
BnO
BnO
O
O
OBn
OPMP
O
OBz
O
OBz
OBn
OBn
BnO
21
Scheme 5. Reagents and conditions: (i) BzCl, toluene-py, 0 °C, 1.5 h, 69%; ii) abs
CH2Cl2, NIS–TMSOTf, ꢀ45 °C, 1 h, 94%; iii) 1 M HCl, MeOH, 50 °C, 3 h, 89%; (iv) (a)
donor 4, AgOTf, abs CH2Cl2, 0 °C, 12 h, 59% for 21, 28% for 7 + 8; (b) donor 2, MeOTf,
abs CH2Cl2, rt, 33% for 21, 38% for 7 + 8; (c) donor 2, NIS–TfOH, abs CH2Cl2, rt, 10%
for 21, 42% for 7 + 8.
3.3. General method B for glycosylation of MeOH with halide
donor 3 or 4
(I) To a solution of MeOH (15 equiv) in toluene (2.5 mL) 3 Å
molecular sieves and AgOTf (2 equiv) were added and it was stirred
for 3 h. The reaction mixture was cooled to the appropriate tem-
perature then the solution of donor (1 equiv) in dry CH2Cl2
(2 mL/0.3 mmol) was added. When TLC showed complete conver-
sion of the donor, the insoluble materials were removed by filtra-
tion, the filtrate was diluted with CH2Cl2, washed with 10%
Na2S2O3-solution and water, filtered, dried and concentrated. The
ratio of the products was determined from the crude product by
HPLC.
(II) A mixture of MeOH (15 equiv) in dry CH3CN (2.5 mL), pow-
dered 3 Å molecular sieves and (HgCN)2 (1 equiv) or Hg(CN)2
(1.5 equiv) and HgBr2 (0.5 equiv) was stirred for 3 h. The reaction
mixture was cooled to 0 °C then the solution of donor (1 equiv)
in dry CH2Cl2 (2 mL/0.3 mmol) was added. When TLC showed com-
plete conversion of the donor, the insoluble materials were re-
moved by filtration, the filtrate was diluted with CH2Cl2, washed
with 10% Na2S2O3-solution and water, filtered, dried and concen-
trated. The ratio of the products was determined from the crude
product by HPLC.
2 and chlorosugar 4, as to consider their capacity in forming a tet-
rasaccharide. Based on our glycosylation experiments discussed
above, higher yield was expected using donor 4.
In the reactions of thioglycoside 2 elimination took place dom-
inantly and the desired tetrasaccharide formed only in moderate
yields. Glycosylation of 20 with the chloride donor 4 resulted in
the target compound 21 in considerably higher yield, according
to our expectation.
In conclusion, this investigation of glycosylation reactions of the
ethylthio, bromo and chloro derivatives of 1-deoxy-1-ethoxysulfo-
nyl-hept-2-ulopyranose revealed, that activation methods and
reactivity of the donors should be matched to the reactivity of
acceptors in order to achieve high yield in glycosylations. Glycosyl
chloride donor 4 with moderate reactivity was applied successfully
to glycosylate a trisaccharide acceptor affording a new sialyl Lewis
X mimetic in acceptable yield. Further exploitation of glycosylation
with anomeric sulfonomethyl-containing donors in synthesis of
oligosaccharides of potential biological activity is in progress in
our laboratory.
3. Experimental
3.4. General method C for preparation of glycosides 5, 6, 10, 11,
14 and 15 starting from donor 2
3.1. General methods
To a solution of acceptor (1.5 equiv) and donor (1 equiv) in dry
CH2Cl2 (15 mL/mmol) 4 Å molecular sieves were added and it was
stirred for 3 h. The reaction mixture was cooled to the appropriate
temperature then the solution of NIS (1.2 equiv) and TfOH
Optical rotations were measured at room temperature with a
Perkin–Elmer 241 automatic polarimeter. TLC was performed on
Kieselgel 60 F254 (Merck) with detection by immersing into 5% eth-

M. Csávás et al. / Carbohydrate Research 346 (2011) 1527–1533
1531
(0.4 equiv) in dry CH2Cl2 and THF (1:1, 2 mL) was added. When TLC
showed complete conversion of the donor, the reaction was
quenched with Et3N, the insoluble materials were removed by fil-
tration, the filtrate was diluted with CH2Cl2, washed with water, fil-
tered, dried and concentrated. The obtained crude product was
used for HPLC measurements.
5.04 (m, 7H, J 11.9 Hz, CH2Ph), 4.59 (d, 1H, J 9.2 Hz), 4.50 (d, 1H, J
12.1 Hz, CH2Ph), 4.28–4.13 (m, 3H, SO3CH2CH3), 4.13–4.06 (m,
1H), 3.80 (d, 1H, J 15.1 Hz, H-1a), 3.82–3.72 (m, 3H), 3.69 (d, 1H,
J 15.1 Hz, H-1b), 1.22 (t, 3H, J 7.1 Hz, SO3CH2CH3); 13C NMR
(50 MHz, CDCl3) d 138.1, 137.9 (4C, Cq, Ph), 128.5–125.6 (20C,
Ph), 104.3 (C-2), 83.6, 79.8, 76.7, (C-3, C-4, C-5), 75.6, 75.2, 75.1,
73.3 (4C, CH2Ph), 68.0 (2C, C-7, SO3CH2CH3), 57.9 (C-1), 15.0
(SO3CH2CH3); MALDI-TOF m/z Calcd for C37H41ClNaO8S+ [M+Na]+:
703.21, Found: 703.21.
3.5. General method D for preparation of glycosides 14 and 15
starting from donor 2 using MeOTf
To a solution of acceptor (1.5 equiv) and donor (1 equiv) in dry
CH2Cl2 (15 mL/mmol) 4 Å powdered molecular sieves were added
and it was stirred for 3 h, then MeOTf (6 equiv) was added. When
TLC showed complete conversion of the donor, the reaction was
quenched with Et3N, the insoluble materials were removed by fil-
tration, the filtrate was diluted with CH2Cl2, washed with water,
filtered, dried and concentrated. The ratio of the products was
determined from the crude product by HPLC.
3.9. 2,6-Anhydro-3,4,5,7-tetra-O-benzyl-1-ethoxysulfonyl-
gluco-hept-2-enitol (8)
D-
Isolated as a colourless syrup (14%) from the reaction of 4 and 9
according to general method E, II, using Hg(CN)2 as a promoter.
[a
]
D
ꢀ4.3 (c 0.07, CHCl3); Rf 0.60 (99:1 CH2Cl2–acetone); 1H NMR
(400 MHz, CDCl3: d 7.34–7.25 (m, 20H, Ph), 4.85–4.48 (m, 8H,
CH2Ph), 4.39 (d, 1H, J 4.2 Hz, H-4), 4.27–4.21 (m, 3H, H-6,
SO3CH2CH3), 4.06–3.97 (m, 3H, H-5, C-1-CH2), 3.83–3.75 (m, 2H,
C-7a,b), 1.25 (t, 3H, J 7.1 Hz, SO3CH2CH3); 13C NMR (100 MHz,
CDCl3): d 137.9, 137.7, 137.6, 136.9 (4C, Cq, Ph), 136.1, 135.7 (C-2
and C-3), 128.4–127.6 (20C, Ph), 76.5 (C-6), 73.5 (C-4), 72.6 (C-5),
73.6, 73.4, 72.5, 70.4 (4C, 4 ꢂ CH2Ph), 67.9 (SO3CH2CH3), 67.8 (C-
7), 49.7 (C-1), 15.0 (SO3CH2CH3); Anal. Calcd for C37H40O8S
(644.77): C, 68.92; H, 6.25; S, 4.97. Found: C, 68.79; H, 6.29; S, 5.00.
3.6. General method E for preparation of glycosides 5, 6, 10, 11,
14 and 15 with halide donors 3 and 4
(I) To a solution of acceptor (1.5 equiv) in toluene (2.5 mL) 4 Å
molecular sieves and AgOTf (2 equiv) were added and it was stirred
for 3 h. The reaction mixture was cooled to the appropriate tem-
perature then the solution of donor (1 equiv) in dry CH2Cl2
(2 mL/0.3 mmol) was added. When TLC showed complete conver-
sion of the donor, the insoluble materials were removed by filtra-
tion, the filtrate was diluted with CH2Cl2, washed with 10%
Na2S2O3-solution and water, filtered, dried and concentrated. The
ratio of the products was determined from the crude product by
HPLC.
(II) A mixture of acceptor (1.5 equiv) in dry CH3CN (2.5 mL),
powdered 4 Å molecular sieves and (HgCN)2 (1 equiv) or Hg(CN)2
(1.5 equiv) and HgBr2 (0.5 equiv) was stirred for 3 h. The reaction
mixture was cooled to 0 °C then the solution of donor (1 equiv)
in dry CH2Cl2 (2 mL/0.3 mmol) was added. When TLC showed com-
plete conversion of the donor, the insoluble materials were re-
moved by filtration, the filtrate was diluted with CH2Cl2, washed
with 10% Na2S2O3-solution and water, filtered, dried and concen-
trated. The ratio of the products was determined from the crude
product by HPLC.
3.10. Methyl 2,3,6-tri-O-benzyl-4-O-(3,4,5,7-tetra-O-benzyl-1-
deoxy-1-ethoxysulfonyl-a-D-gluco-hept-2-ulopyranosyl)-b-D-
glucopyranoside (14)
Compound 14 was prepared from donor 2 and acceptor 12 by
method C and donor 3 or 4 and acceptor 12 by method E (see Table
3). [a]
+33.1 (c 0.19, CHCl3); Rf 0.69 (98:2 CH2Cl2–acetone); 1H
D
NMR (500 MHz, CDCl3 d 7.33–7.14 (m, 35H, Ph), 4.95–4.84 (m,
5H, CH2Ph), 4.77 (d, 1H, J 11.1 Hz, CH2Ph), 4.66 (d, 1H, J 11.2 Hz,
CH2Ph), 4.60–4.57 (m, 5H, H-1, CH2Ph), 4.51–4.42 (m, 3H, CH2Ph),
4.21–4.14 (m, 4H, H-10a, H-50, H-60, H-70a), 4.05 (t, 1H, J 9.0 Hz,
H-4), 4.00 (dd, 1H, J 10.0 Hz, J 5.0 Hz, H-30), 3.91–3.89 (m, 1H, H-
3), 3.86 (q, 2H, J 7.0 Hz, SO3CH2CH3), 3.73–3.70 (m, 3H, H-10b, H-
5, H-6a), 3.67–3.62 (m, 2H, H-40, H-6b), 3.55 (d, 1H, J 11.3 Hz, H-
70b), 3.45 (dd, 1H, J1,2 3.3 Hz, J2,3 9.5 Hz, H-2), 3.36 (s, 3H, OCH3),
1.08 (t, 3H, J 7.05 Hz, SO3CH2CH3); 13C NMR (125 MHz, CDCl3
d
139.1–137.8 (7C, Cq, Ph), 128.6–126.8 (35C, Ph), 99.9 (C-20), 97.3
(C-1), 82.4 (C-50), 81.0 (C-3), 80.4 (C-60), 79.4 (C-2), 78.5 (C-40),
73.2 (C-4), 73.0 (C-30), 70.3 (C-5), 75.4, 75.3, 75.2, 73.3, 73.2, 73.1
3.7. 3,4,5,7-Tetra-O-benzyl-1-deoxy-1-ethoxysulfonyl-
a-D-
gluco-hept-2-ulopyranosyl-bromide (3)
(7C, CH2Ph), 69.5 (C-70), 68.9 (C-6), 66.7 (SO3CH2CH3), 55.4
3
(OCH3), 51.5 (C-10, JC1 ,H3 6 1 Hz), 14.8 (SO3CH2CH3); Anal. Calcd
for C65H72O14S (1109.32): C, 70.38; H, 6.54; S, 2.89. Found: C,
69.96; H, 6.33; S, 2.76.
0
0
To a stirred solution of 2 (212 mg, 0.30 mmol) in abs dichloro-
methane (2 mL), 15 L (0.30 mmol, 1.0 equiv) bromine was added
l
and it was cooled to 0 °C. The reaction mixture was concentrated
after 10 min and the residue was coevaporated three times with
toluene. The obtained syrupy crude product (218 mg) was used
for further reaction without purification. Rf 0.75 (98:2 CH2Cl2–
acetone).
3.11. 4-Methoxyphenyl 2,3,6-tri-O-benzyl-4-O-(3,4,5,7-tetra-O-
benzyl-1-deoxy-1-ethoxysulfonyl-a-D-gluco-hept-2-
ulopyranosyl)-b- -glucopyranoside (15)
D
3.8. 3,4,5,7-Tetra-O-benzyl-1,2-dideoxy-1-ethoxysulfonyl-
gluco-hept-2-ulopyranosyl-chloride (4)
a-D
-
Compound 15 was prepared from donor 2 and acceptor 13 by
method C and from donor 3 or 4 and acceptor 13 by method E
(see Table 4). [a] +9.8 (c 0.17, CHCl3); Rf 0.85 (97:3 CH2Cl2–ace-
D
Compound 1 (700 mg, 0.99 mmol) was dissolved in 5 mL abs
dichloromethane and 55 L (0.99 mmol, 1.0 equiv) pyridine and
85 L (1.09 mmol, 1.1 equiv) SOCl2 were added at room tempera-
ture. After 10 min the reaction mixture was diluted with CH2Cl2,
washed twice with 1 M aq HCl, 1 M aq NaHCO3 and water, then
it was dried, filtered, evaporated and purified by column chroma-
tography, to give 4 (625 mg, 85%). For glycosylation, the syrupy
crude product was used without purification. Rf 0.81 (n-hexane–
EtOAc 7:3); 1H NMR (200 MHz, CDCl3): d 7.38–7.12 (m, 20H, Ph),
tone); 1H NMR (500 MHz, CDCl3 d 7.34–7.16 (m, 35H, Ph), 6.98,
6.79 (2 ꢂ d, 4H, PMP), 5.07 (d, 1H, J 6.3 Hz), 4.98–4.41 (m, 14H,
CH2Ph), 4.23 (d, 1H, J 9.6 Hz), 4.17–4.11 (m, 3H), 3.96–3.89 (m,
5H), 3.75 (s, 3H, OCH3), 3.71–3.59 (m, 7H), 1.10 (t, 3H, J 7.1 Hz,
SO3CH2CH3); 13C NMR (125 MHz, CDCl3 d 155.1, 151.2 (2C, Cq,
PMP), 138.4–138.0 (7C, Cq, Ph), 128.3–127.1 (35C, Ph), 118.1,
114.5 (4C, PMP), 102.0 (C-1), 100.1 (C-20), 82.5, 80.5, 80.1, 78.3,
76.6, 73.3, 73.2 (skeleton carbons) 75.3, 75.2, 75.0, 74.6, 74.1,
73.4, 73.3 (6C, CH2Ph), 70.1, 68.9 (C-6 and C-70), 67.0 (SO3CH2CH3),
l
l

1532
M. Csávás et al. / Carbohydrate Research 346 (2011) 1527–1533
3
55.5 (OCH3), 51.8 (C-10, JC1 ,H3 6 1 Hz), 14.9 (SO3CH2CH3); Anal.
Calcd for C71H76O15S (1200.49): C, 70.98; H, 6.38; S, 2.67. Found:
C, 71.04; H, 6.43; S, 2.59.
(1.1 g, 89%) as a colourless syrup. [
a
]
ꢀ11.6 (c 0.96, CHCl3); Rf
0
0
D
0.52 (9:1 CH2Cl2–EtOAc); 1H NMR (200 MHz, CDCl3 d 8.12–6.98
(m, 35H, Ph), 6.81–6.52 (m, 4H, PMP), 5.69 (t, 1H, J 9.0 Hz, H-2),
5.40 (d, 1H, J1 ,2 3.5 Hz, H-100), 5.25 (t, 1H, J 9.0 Hz, H-20), 4.89–
00 00
3.12. 4-Methoxyphenyl 3,4-O-isopropylidene-2,6-di-O-benzoyl-
4.53 (m, 11H), 4.39–4.07 (m, 6H), 3.99–3.53 (m, 7H), 3.63 (s, 3H,
OCH3), 1.32 (d, 3H, H-600); 13C NMR (50 MHz, CDCl3 d 166.5,
166.2, 166.0, 164.5 (4C, CO), 155.3, 151.1 (2C, Cq, PMP), 139.1–
126.7 (35C, Ph), 118.6, 114.2 (4C, PMP), 100.9 (C-1), 100.1 (C-10),
97.6 (C-100), 78.9, 78.3, 75.4, 74.4, 73.5, 71.8, 67.7, 66.5 (skeleton
carbons), 75.1, 72.6 (3C, CH2Ph), 62.9, 61.7 (C-6 and C-60), 55.4
(OCH3), 16.5 (C-600). Anal. Calcd for C74H72O20 (1280.46): C, 69.36;
H, 5.66. Found: C, 66.34; H, 5.65.
b-D-galactopyranosyl-(1?4)-2,6-di-O-benzoyl-b-D-
glucopyranoside (17)
A stirred solution of 16 (970 mg, 2 mmol) in 15 mL of dry pyri-
din and 20 mL of dry toluene was cooled to 0 °C and BzCl (1.85 ml,
16 mmol, 8 equiv) was added dropwise. After 90 min MeOH was
added and the reaction mixture was concentrated. It was then di-
luted with EtOAc, washed with satd aq NaHCO3 and water, dried,
filtered and evaporated. The crude product was recrystallized from
3.15. 4-Methoxyphenyl 3,4,5,7-tetra-O-benzyl-1-deoxy-1-
EtOAc–n-hexane to yield 17 (1.25 g, 69%). Mp 225–227 °C, [
a
]
ethoxysulfonyl-
benzoyl-b- -galactopyranosyl-(1?4)-2,6-di-O-benzoyl-3-O-
(2,3,4-tri-O-benzyl- -fucopyranosyl)-b- -glucopyranoside (21)
a-D-gluco-hept-2-ulopyranosyl-(1?3)-2,6-di-O-
D
+7.6 (c 0.54, CHCl3); Rf 0.73 (95:5 CH2Cl2–acetone); 1H NMR
(200 MHz, DMSO-d6 d 8.09–7.29 (m, 20H, Ph), 6.82, 6.59 (2 ꢂ d,
4H, PMP), 5.46 (t, 1H, J 8.5 Hz),5.38 (t, 1H, J 7.6 Hz), 4.7 (d, 1H,
J1,2 8.0 Hz,), 4.87 (d, 1H, J 10.8 Hz), 4.69–4.66 (m, 2H), 4.47–4.28
(m, 6H), 4.06 (t, 1H, J 9.2 Hz), 3.84–3.75 (m, 2H), 3.65 (s, 3H,
OCH3), 1.64, 1.35 (2 ꢂ s, 6H, C(CH3)2); 13C NMR (50 MHz, DMSO d
166.5, 165.4, 165.2 (4C, CO), 155.4, 151.0 (2C, Cq, PMP), 133.3–
128.4 (24C, Ph), 118.7, 114.2 (4C, PMP), 111.2 (C(CH3)2), 101.4
(C-1), 100.5 (C-10), 82.4, 76.9, 73.5, 73.4, 72.9, 72.7, 72.1, 72.0 (skel-
eton carbons), 63.6, 62.7 (C-6 and C-60), 55.4 (OCH3), 27.5, 26.2
(C(CH3)2); Anal. Calcd for C50H48O16 (904.29): C, 66.36; H, 5.35.
Found: C, 66.37; H, 5.34.
D
a-L
D
To a stirred solution of acceptor 20 (750 mg, 0.57 mmol) and
donor 4 (267 mg, 0.38 mmol) in dry CH2Cl2 (10 mL) 4 Å molecular
sieves were added. After stirring for 1 h the mixture was cooled to
0 °C and AgOTf (74 mg, 2 equiv) dissolved in toluene (2 mL) was
added. The mixture was kept at 0 °C overnight. Insoluble materials
were removed by filtration, the filtrate was diluted with CH2Cl2,
washed with 10% aq Na2S2O3 and water, dried, filtered and concen-
trated. The crude product was purified by column chromatography
(6:4 n-hexane–EtOAc) to yield 21 (710 mg, 59%) as a colourless
syrup.
3.13. 4-Methoxyphenyl 2,6-di-O-benzoyl-3,4-O-isopropylidene-
Compound 21 was also prepared from acceptor 20 (250 mg,
0.19 mmol, 1.5 equiv) and donor 2 (92 mg, 0.13 mmol, 1 equiv) in
dry CH2Cl2 (10 mL) by method D using MeOTf (86 lL, 0.78 mmol,
b-D
-galactopyranosyl-(1?4)-2,6-di-O-benzoyl-3-O-(2,3,4-tri-O-
-fucopyranosyl)-b- -glucopyranoside (19)
benzyl-a-
L
D
6 equiv). The crude product was purified by column chromatogra-
phy (9:1 toluene–acetone) to yield 21 (82 mg, 33%) as a colourless
syrup.
Compound 21 was also prepared from acceptor 20 (250 mg,
0.19 mmol, 1.5 equiv) and donor 2 (92 mg, 0.13 mmol, 1 equiv) in
dry CH2Cl2 (10 mL) by method C using NIS (35 mg, 1.2 equiv) and
To a stirred solution of acceptor 17 (1.1 g, 1.22 mmol) and donor
18 (0.875 g, 1.83 mmol) in dry CH2Cl2 (20 mL) 4 Å molecular sieves
was added. After stirring for 1 h the mixture was cooled to ꢀ45 °C
and NIS (36 mg, 1.3 equiv) and TMSOTf (66 lL, 0.3 equiv) dissolved
in CH2Cl2–THF (1:1, 5 mL) were added. After 1 h the reaction was
quenched with pyridine (0.5 mL), diluted with CH2Cl2 and filtered
through Celite. The filtrate was washed with 10% aq Na2S2O3 and
water, dried and concentrated. The crude product was purified
by column chromatography (99:1 CH2Cl2–acetone) to yield 19
TfOH (4.7
lL, 0.05 mmol, 0.4 equiv). The crude product was purified
by column chromatography (9:1 toluene–acetone) to yield 21
(25 mg, 10%) as a colourless syrup. [a] +24.4 (c 0.38 CHCl3); Rf
D
0.37 (9:1 toluene–acetone); 1H NMR (400 MHz, CDCl3 d 8.15–7.00
(m, 55H, Ph), 6.74, 6.55 (2 ꢂ d, 4H, PMP), 5.61 (t, 1H, J2,3 8.2 Hz,
(1.51 g, 94%) as a colourless syrup. [a] +13.56 (c 0.649, CHCl3);
D
Rf 0.42 (n-hexane–EtOAc 7:3); 1H NMR (500 MHz, CDCl3 d 8.12–
6.90 (m, 35H, Ph), 6.65, 6.47 (2 ꢂ d, 4H, PMP), 5.58 (t, 1H, J
H-1), 5.47 (t, 1H, J2 ,3 8.9 Hz, H-10), 5.41 (d, 1H, J1 ,2 3.5 Hz, H-100),
4.98–4.17 (m, 28H, 7 ꢂ CH2Ph, H-500, H-1, H-10, H-6a,b, H-60a,b, H-
400, H-7000a,b, H-6000, H-3, H-4000, H-300), 4.11–3.98 (m, 4H, H-4, H-30,
SO3CH2CH3), 3.95–3.84 (m, 2H, H-200, H-5000), 3.78–3.57 (m, 4H, H-
40, H-3000, H-5, H-50), 3.64 (s, 3H, OCH3), 3.28 (s, 1H, H-40-OH),
0
0
00 00
8.8 Hz), 5.38 (d, 1H, J1 ,2 3.5 Hz, H-100), 5.19 (t, 1H, J 8.0 Hz),
00 00
4.90–4.69 (m, 6H), 4.61–4.44 (m, 4H), 4.33–4.18 (m, 6H), 4.11–
4.02 (m, 2H), 3.90–3.89 (m, 2H), 3.73 (s, 1H), 3.58–3.54 (m, 1H),
3.53 (s, 3H, OCH3), 1.43, 1.24 (2 ꢂ s, 6H, C(CH3)2), 1.20 (d, 3H, H-
600); 13C NMR (125 MHz, CDCl3 d 166.3, 165.8, 164.6, 164.4 (4C,
CO), 155.4, 151.0 (2C, Cq, PMP), 139.0. 138.5, 138.0 (3C, Cq, Ph),
133.3–126.7 (39C, Ph), 118.6, 114.2 (4C, PMP), 110.7 (C(CH3)2),
100.8 (C-1), 100.3 (C-10), 97.3 (C-100), 79.0, 78.1, 75.5, 73.9, 73.4,
73.2, 73.1, 71.3, 66.4 (skeleton carbons), 74.5, 72.5 (3C, CH2Ph),
62.5 (C-6 and C-60), 55.3 (OCH3), 27.6, 26.2 (C(CH3)2), 16.8 (C-600).
Anal. Calcd for C77H76O20 (1320.49): C, 69.99; H, 5.80. Found: C,
66.97; H, 5.78.
3.15–3.04 (m, 2H, H-1000a,b), 1.40 (d, 3H, J5 ,6 6.5 Hz, H-600), 1.10 (t,
00 00
3H, J 7.0 Hz, SO3CH2CH3); 13C NMR (100 MHz, CDCl3 d 166.3,
165.9, 164.4 (4C, CO), 155.4, 151.1 (2C, Cq, PMP), 139.3–137.3 (7C,
Cq, Ph), 129.8–126.7 (55C, Ph), 118.7, 114.2 (4C, PMP), 100.1,
100.4, 97.7 (C-1, C-10, C-100), 99.8 (C-2000), 82.8, 82.4, 80.9, 78.9,
78.8, 77.9, 75.6, 74.5, 74.4, 73.5, 72.8, 71.9, 71.5, 70.6, 67.8, 66.6,
(skeleton carbons), 75.2, 75.1, 74.9, 73.4, 73.1, 72.6, 72.3 (7C,
CH2Ph), 68.4, 68.1 (C-6000, SO3CH2CH3), 62.6, 62.2 (C-6, C-60), 55.4
(OCH3), 53.3 (C-1000, 3JC1
MALDI-TOF m/z Calcd for
6 1 Hz), 16.5 (C-600), 15.0 (SO3CH2CH3).
000,H3000
C111H112NaO28S
[M+Na]+: 1947.70,
3.14. 4-Methoxyphenyl 2,6-di-O-benzoyl-b-
(1?4)-2,6-di-O-benzoyl-3-O-(2,3,4-tri-O-benzyl-
fucopyranosyl)-b- -glucopyranoside (20)
D
-galactopyranosyl-
Found: 1948.25. Anal. Calcd for C111H112O28S (1924.71): C, 69.22;
H, 5.86; S, 1.66. Found: C, 69.21; H, 5.84; S, 1.64.
a-L-
D
Acknowledgements
A solution of 19 (1.3 g, 0.19 mmol) in MeOH (25 mL) was trea-
ted with 2.5 mL 1 M aq HCl at 50 °C for 3 h. The mixture was con-
centrated, diluted with CH2Cl2, washed with satd aq NaHCO3 and
water, dried, filtered and evaporated. The crude product was puri-
fied by column chromatography (9:1 CH2Cl2–EtOAc) to yield 20
This work was supported by the TÁMOP 4.2.1/B-09/1/KONV-
2010-0007 project. The project was co-financed by the European
Union and the European Social Fund. Financial support of the Hun-
garian Research Fund (K 62802) is also acknowledged.

M. Csávás et al. / Carbohydrate Research 346 (2011) 1527–1533
1533
7. Borbás, A.; Szabovik, G.; Antal, Z.; Herczegh, P.; Agócs, A.; Lipták, A. Tetrahedron
Lett. 1999, 40, 3639–3642.
References
8. Borbás, A.; Szabovik, G.; Antal, Z.; Fehér, K.; Csávás, M.; Szilágyi, L.; Herczegh,
P.; Lipták, A. Tetrahedron: Asymmetry 2000, 11, 549–566.
9. Jeanjean, A.; Gary-Bobo, M.; Nirdé, P.; Leiris, S.; Garcia, M.; Morère, A. Bioorg.
Med. Chem. Lett. 2008, 18, 6240–6243.
10. Unpublished results. Related articles: (a) Herczeg, M.; Lázár, L.; Borbás, A.;
Lipták, A. Org. Lett. 2009, 11, 2619–2622; (b) Lázár, L.; Herczeg, M.; Fekete, A.;
Borbás, A.; Lipták, A.; Antus, S. Tetrahedron Lett. 2010, 51, 6711–6714.
11. Lipták, A.; Jodál, I.; Nánási, P. Carbohydr. Res. 1975, 44, 1–11.
12. Meijer, A.; Ellervik, U. J. Org. Chem. 2004, 69, 6249–6256.
13. Májer, G.; Borbás, A.; Illyés, T. Z.; Szilágyi, L.; Bényei, A.; Lipták, A. Carbohydr.
Res. 2007, 342, 1393–1404.
14. Borbás, A.; Csávás, M.; Szilágyi, L.; Májer, G.; Lipták, A. J. Carbohydr. Chem. 2004,
23, 133–146.
15. Tsukida, T.; Yoshida, M.; Kurokawa, K.; Nakai, Y.; Achiha, T.; Kiyoi, T.; Kondo, H.
J. Org. Chem. 1997, 62, 6876–6881.
16. Peters, T.; Weimar, T. Liebigs Ann. Chem. 1991, 3, 237–242.
17. Wegman, B.; Schmidt, R. R. Carbohydr. Res. 1988, 184, 254–261.
1. Varki, A. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 7390–7397.
2. (a) Stahl, W.; Sprengard, U.; Kretzschmar, G.; Schmidt, W. D.; Kunz, H. J. Prakt.
Chem. 1995, 337, 441–445; (b) Sprengard, U.; Kretzschmar, G.; Bartnik, E.; Hüls,
C.; Kunz, H. Angew. Chem., Int. Ed. Engl. 1995, 107, 990–993.
3. (a) Simanek, E. E.; McGarvey, G. J.; Jablonowski, J. A.; Wong, C.-H. Chem. Rev.
1998, 98, 833–862; (b) Kaila, N.; Thomas, B. E., IV Med. Res. Rev. 2002, 22, 566–
601; (c) Barbaro, J. Curr. Org. Chem. 2004, 8, 883–902; (d) Pedatella, S.; De Nisco,
M.; Ernst, B.; Guaragna, A.; Wagner, B.; Woods, R. J.; Palumbo, G. Carbohydr. Res.
2008, 343, 31–38; (e) Gouge-Ibert, V.; Pierry, C.; Poulain, F.; Serre, A.-L.;
Largeau, C.; Escriou, V.; Scherman, D.; Jubault, P.; Quirion, J.-C.; Leclerc, E.
Bioorg. Med. Chem. Lett. 2010, 20, 1957–1960.
4. (a) Ellervik, U.; Magnusson, G. Bioorg. Med. Chem. 1994, 2, 1261–1266; (b) Jain,
R. K.; Vig, R.; Locke, R. D.; Mohammad, A.; Matta, K. L. J. Chem. Soc., Chem.
Commun. 1996, 65–67; (c) Nicolaou, K. C.; Bockovich, N. J.; Carcanague, D. R. J.
Am. Chem. Soc. 1993, 115, 8843–8844; (d) Koenig, A.; Jain, R.; Vig, R.; Norgard-
Sumnicht, K. E.; Matta, K. L.; Varki, A. Glycobiology 1997, 7, 79–93.
5. Wong, C.-H.; Moris-Varas, F.; Hung, S. C.; Marron, T. G.; Lin, C. C.; Gong, K. W.;
Weitz-Schmidt, G. J. Am. Chem. Soc. 1997, 119, 8152–8158.
6. Thoma, G.; Magnani, J. L.; Patton, J. T.; Ernst, B.; Jahnke, W. Angew. Chem., Int.
Ed. 2001, 40, 1941–1945.