First synthesis of 3′-deoxy Lewisx pentasaccharide

Article abstract of DOI:10.1016/j.tetasy.2005.08.007

The total synthesis of 3′-deoxy Lewis^x pentasaccharide is reported. 4-O-Acetyl-2,6-di-O-benzoyl-3-deoxy-β-d-xylo-hexopyranosyl trichloroacetimidate was condensed with a diol of glucosamine to give a disaccharide, which was further fucosylated t

Full text of DOI:10.1016/j.tetasy.2005.08.007

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 3024–3029
First synthesis of 30-deoxy Lewisx pentasaccharide
Chafika Gourmala,a,b,c Zhenyuan Zhu,a Yun Luo,a,d Bo Tao Fan,b
Sa¨ıd Ghalem,c Yongzhou Hud and Yongmin Zhanga,d,
*
aEcole Normale Supe´rieure, De´partement de Chimie, CNRS-UMR 8642, 24 rue Lhomond, 75231 Paris Cedex 05, France
b
`
Interfaces, Traitements, Organisation et Dynamique des Systemes (ITODYS) CNRS-UMR 7086,
Universite´ Paris 7-Denis Diderot, 1 rue Guy de la Brosse, 75005 Paris, France
cLaboratoire de Chimie Organique, Substances Naturelles et Analyse, BP 119, 13000, Universite´ de Tlemcen, Algeria
dZJU-ENS Joint Laboratory of Medicinal Chemistry, Zhejiang University, Hubin Campus, Hangzhou 310031, China
Received 24 June 2005; accepted 4 August 2005
Available online 9 September 2005
Abstract—The total synthesis of 30-deoxy Lewisx pentasaccharide is reported. 4-O-Acetyl-2,6-di-O-benzoyl-3-deoxy-b-D-xylo-hexo-
pyranosyl trichloroacetimidate was condensed with a diol of glucosamine to give a disaccharide, which was further fucosylated to a
Lewisx trisaccharide analogue. Glycosylation of a lactoside diol with this trisaccharide provided a pentasaccharide, which after
deprotection, afforded the target pentasaccharide.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
sion. One of the structures involved in this mechanism is
the Lewisx (Lex) trisaccharide determinant.
Carbohydrates are the most ubiquitous and prominently
exposed molecules on the surface of living cells. They
have been recognized as interaction sites in many differ-
ent instances. Many of these processes are mediated by
lectin or lectin-like molecules that recognize specific
carbohydrate motifs. Recent advances in glycobiology
revealed the existence of biologically significant carbo-
hydrate–carbohydrate interactions, and this type of
interaction could have a general, fundamental character
for cell biology.1 A typical example is the report of Hako-
mori,2 who proposed that carbohydrate–carbohydrate
interaction is responsible for the initial step of cell adhe-
The interaction between Lex and Lex was found3,4 to be
homotypic, and mediated by the presence of divalent
cations such as Ca2+. Recently, the Lex–Lex interaction
has gained increasing attention, using a variety of tech-
niques including nuclear magnetic resonance (NMR)
spectroscopy,5 mass spectrometry (MS),6 vesicle adhe-
sion,7 atomic force microscopy (AFM),8 and surface
plasmon resonance (SPR) spectroscopy.9 Rat basophilic
leukaemia cells pre-incubated with purified Lex contain-
ing glycosphingolipids have also been used as a model.10
However, in these studies the local environment of the
Lex was always very different from that existing at a typ-
ical cell surface. In cells, the Lex-bearing molecules are
usually composed of a ceramide connected to the Lex
trisaccharide through a lactose group. Very recently,
using a chemically synthesized natural Lex, we demon-
strated by a vesicle approach that unlike the neoglyco-
lipids,7 which allowed a strong orientational freedom
of the Lex group, the natural lipid showed a restricted
orientation of the Lex group by which the adhesion
induced by Lex–Lex interaction was considerably
enhanced.11 Another experiment was performed by
replacing the Lex by Lea in which the galactose and fu-
cose are permutated relative to the Lex on one vesicle
surface. The weak adhesion energy obtained for Lex–
Lea pair showed clearly that the permutation of the
HO
OH
OH
O
O
O
HO
OH
OH
O
NHAc
H C
3
O
OH
OH
HO
Lex trisaccharide
*
Corresponding author. Tel.: +33 1 44323335; fax: +33 1 44323397;
e-mail: yongmin.zhang@ens.fr
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.08.007

C. Gourmala et al. / Tetrahedron: Asymmetry 16 (2005) 3024–3029
3025
HO
OH
HO
OH
OH
O
OH
O
O
d
O
c
O
b
O
HO
O
O
OH
a
OSE
OH
NHAc
OH
H3C
HO
O
e
OH
OH
1
fucose and galactose residues in the trisaccharide head-
group effectively prevents specific adhesion.11
disaccharide 6 in 75% yield (Scheme 2). Such a selective
behaviour of phenyl 6-O-benzyl-2-deoxy-2-phthalimido-
1-thio-b-D-glucopyranoside
observed during its glycosylation with 2,3,4,6-tetra-O-
benzoyl-a-D-galactopyranosyl Another
bromide.15
5 has previously been
In order to understand the key role of the different hy-
droxyl groups on Lex trisaccharide, it is important to
have a series of pentasaccharides available in which
one of the eight hydroxyl groups is replaced by a hydro-
gen atom, and to test the induced adhesion by interac-
tion of these derivatives. Herein, we report the first
total synthesis of 30-deoxy Lewisx pentasaccharide 1 to
be used for a tool of carbohydrate–carbohydrate inter-
action study.
example for this type of regioselective glycosylation
was reported for phenyl 2,3,4 tri-O-acetyl-6-O-benzyl-
1-thio-b-D-galactopyranoside.16 The 1H NMR spectrum
of 6 showed the presence of the H-3c of the glucosamine
residue at d 4.59 (ddd, J2,3 = 10.3 Hz, J3,4 = 8.2 Hz,
J3,OH = 1.0 Hz), indicating that the position of the new-
ly formed glycosidic linkage in the disaccharide 6 to be
at OH-4 of the acceptor 5. This regioselectivity was
1
further confirmed from the H NMR spectrum of 60—
2. Results and discussion
obtained from 6 by acetylation—which revealed a
deshielded signal for H-3c at 5.77 ppm (t, J2,3
=
A key building block in the synthesis of pentasaccharide
J3,4 = 9.4 Hz), therefore confirming the position of the
new glycosidic linkage in 6 as being OH-4 of the diol
5. Its stereochemistry was determined to be the desired
b-form on the basis of the H-1d, H-2d coupling constant
(J1d,2d = 8.1 Hz).
1
was 4-O-acetyl-2,6-di-O-benzoyl-3-deoxy-b-D-xylo-
hexopyranosyl trichloroacetimidate 4, which can be
readily prepared from the known phenyl 4-O-acetyl-
2,6-di-O-benzoyl-3-deoxy-1-thio-b-D-xylo-hexopyrano-
side 2,12 by treatment with (i) BF3ÆEt2O/HgO and (ii)
Cl3CCN/DBU, without further characterization of the
intermediate hemiacetal 3, in 67% yield (for two steps),
as shown in Scheme 1. NMR spectra showed that the
imidate was formed essentially in the a-form.
The fucosylation of 6 with ethyl 2,3,4-tri-O-benzyl-
1-thio-b-L-fucopyranoside 717 in the presence of N-
iodosuccinimide (NIS)—trifluoromethanesulfonic acid
(TfOH) in toluene for 1 h at À25 °C gave the
expected trisaccharide 8 in 70% yield (Scheme 3). The
stereochemistry of the newly introduced glycosidic
linkage was determined to be a on the basis of the
low value of the Fuc H-1, H-2 coupling constant
(J1e,2e = 3.5 Hz).
Condensation of trichloroacetimidate 4 with the previ-
ously described diol 5,13 according to Schmidtꢀs meth-
od,14 proceeded regioselectively, taking advantage of
the ꢁstereo hindrance effectꢀ, to give the b1!4 linked
AcO
OBz
AcO
OBz
AcO
OBz
O
ii
i
O
O
SPh
OH
BzO
OBz
CCl3
OBz
O
C
2
3
NH
4
Scheme 1. Reagents and conditions: (i) BF3ÆEt2O, HgO, H2O, THF, 15 min, 70%; (ii) Cl3CCN, DBU, DCM, 0 °C, 1 h, 95%.
OBn
O
AcO
OBz
AcO
OBz
OBn
O
O
O
HO
HO
TMSOTf
SPh
d
O
c
+
SPh
RO
NPhth
OBz
BzO
0 ˚C, 1 h
75%
NPhth
CCl3
O
C
6
R = H
4
5
NH
Ac2/Py
6' R = Ac
Scheme 2.

3026
C. Gourmala et al. / Tetrahedron: Asymmetry 16 (2005) 3024–3029
AcO
OBz
OBn
O
O
AcO
OBz
OBn
O
SPh
HO
O
O
OBz
NPhth
O
SPh
NIS, TfOH
Toluene
O
BzO
6
NPhth
-25˚C, 1h
70%
H3C
BnO
O
SEt
OBn
OBn
O
OBn
OBn
BnO
OBz
8
7
Scheme 3.
AcO
OBn
O
O
HO
O
OBn
OBn
SPh
O
BzO
H3C
O
O
NPhth
O
BnO
HO
OSE
+
O
BnO
OBn
BnO
OBn
BnO
-30oC, 1h
70%
9
8
NIS, TfOH
CH2Cl2
AcO
OBz
HO
OBn
OBn
O
O
OBn
O
d
O
O
O
c
b
O
BnO
O
BzO
e
a
OSE
OBn
NPhth
OBn
H3C
O
OBn
OBn
BnO
10
Scheme 4.
The glycosylation of diol 918 with donor 8 was achieved
under the conditions described above, providing the
desired pentasaccharide 10 in 70% yield (Scheme 4).
The stereochemistry of the newly introduced linkage
was determined to be b on the basis of the GlcN H-1,
H-2 coupling constant (J1c,2c = 8.5 Hz). The regiochem-
istry of 10 was assigned by comparison with a very sim-
ilar reaction.19 In fact, the regioselectivity of 3-OH was
usually observed during the glycosylation of the 3,4-diol
of the galactose moiety, especially using a large glycosyl
donor.20
to the derivative 11 in 80% overall yield from 10.
Catalytic hydrogenolysis of 11 and purification of
the product on Sephadex G25-150 afforded the desired
pentasaccharide
(Scheme 5).
1
in almost quantitative yield
3. Experimental
3.1. General methods
Optical rotations were measured at 20 2 °C with a
Perkin–Elmer Model 241 digital polarimeter, using a
10 cm, 1 mL cell. Chemical ionisation (CI, ammonia)
Treatment of pentasaccharide 10 with hydrazine in
boiling ethanol, followed by acetylation, then led
HO
OH
HO
OBn
OBn
O
OBn
O
O
O
O
i) N2H4, EtOH, H2O
H2, Pd/C, MeOH
98%
O
BnO
O
O
HO
OSE
1
10
OBn
NHAc
OBn
H3C
BnO
O
ii) Ac2O, Py, CH2Cl2
OBn
OBn
11
Scheme 5.

C. Gourmala et al. / Tetrahedron: Asymmetry 16 (2005) 3024–3029
3027
and Fast Atom Bombardment (FAB) mass spectra were
obtained with a JMS-700 spectrometer. Elemental anal-
yses were performed by Service de microanalyze de
4.20 (dd, 1H, J5,6 = 8.6 Hz, H-60d), 4.15 (ddd, 1H,
J4,5 = 1.1 Hz, H-5d), 3.81 (dd, 1H, J4,5 = 9.5 Hz, H-
4c), 3.73 (ddd, 1H, J4,5 = 9.8 Hz, J5,6 = 4.2 Hz,
0
0
´
lꢀUniversite Pierre et Marie Curie, 4 Place Jussieu,
J5;6 ¼ 1.3 Hz, H-5c), 3.693 (dd, 1H, J6;6 ¼ 11 Hz, H-
1
75005 Paris, France. H NMR spectra were recorded
6c), 3.63 (dd, 1H, H-60c), 2.57 (ddd, 1H, J2,3 = 5.2 Hz,
0
with a Bruker DRX 400 spectrometer at ambient tem-
perature. Assignments were aided by COSY experi-
ments. 13C NMR spectra were recorded at 100.6 MHz
with a Bruker DRX 400 for solutions in CDCl3 or
D2O. Flash column chromatography was performed
on silica gel 60 (230–400 mesh, Merck).
J3;3 ¼ 14.3 Hz, J3,4 = 3.1 Hz, H-3d), 2.19 (s, 3H,
0
0
CH3), 1.93 (ddd, 1H, J2;3 ¼ 11.9 Hz, J3 ;4 ¼ 3.1 Hz, H-
30d); 13C NMR (100.6 MHz, CDCl3): d 169.96 (C@O,
Ac), 167.96, 167.41 (2C@O, NPht), 166.19, 164.90
(C@O, Bz), 138.26, 132.14, 131.69, 131.54, 129.28,
128.98 (aromatic C), 133.97, 133.89, 133.45, 133.15,
132.29, 129.72, 129.70, 129.54, 128.93, 128.70, 128.48,
128.43, 128.36, 128.18, 128.12, 127.65, 127.41, 127.28,
125.19, 123.48, 123.19 (aromatic CH), 103.04 (C-1d),
83.28 (C-1c), 82.20 (C-4c), 77.96 (C-5c), 75.10 (C-5d),
72.98 (PhCH2), 70.86 (C-3c), 68.26 (C-6c), 67.65
(C-2d), 67.08 (C-4d), 62.96 (C-6d), 54.95 (C-2c), 32.94
(C-3d), 20.83 (CH3). HRMS (CI, NH3) Calcd for
3.2. 4-O-Acetyl-2,6-di-O-benzoyl-3-deoxy-b-D-xylo-
hexopyranosyl trichloroacetimidate 4
To a solution of 3 (5.16 g, 14.81 mmol) in 220 mL of dry
dichloromethane were added at 0 °C, 17.08 mL of tri-
chloroacetonitrile and 2.23 mL of DBU, dropwise. The
mixture was stirred at 0 °C for 1 h. After concentra-
tion, the residue was purified by flash chromatogra-
phy, eluting with toluene–ethyl acetate–triethylamine
(600:100:0.7) to give compound 4 as a white foam in
95% yield: Rf 0.53 (toluene–ethyl acetate 4:1),
[a]D = +20 (c 0.9, chloroform); 1H NMR (400 MHz,
CDCl3): d 8.59 (s, 1H, NH), 8.01–7.99 (m, 4H, arom),
7.58–7.54 (m, 2H, arom), 7.45–7.40 (m, 4H, arom),
6.65 (d, 1H, J1,2 = 3.2 Hz, H-1), 5.60–5.54 (m, 1H, H-
2), 5.41 (br, 1H, H-4), 4.55–4.51 (m, 1H, H-5), 4.46–
4.37 (m, 2H, H-6a, H-6b), 2.45–2.43 (m, 1H, H-3a),
2.42–2.41 (m, 1H, H-3e), 2.19 (s, 3H, CH3); 13C NMR
(100.6 MHz, CDCl3): d 170.16 (C@O, Ac), 166.03,
165.49 (2C@O, Bz), 160.69 (C@NH), 133.51–128.39
(aromatic C, CH), 93.06 (C-1), 69.57 (C-5), 67.34 (C-
4), 66.52 (C-2), 62.36 (C-6), 28.36 (C-3), 20.96 (CH3).
HRMS Calcd for C24H22Cl3NO8 (M+Na+): 580.0303.
Found 580.0316.
C49H49N2O13S
905.2969.
(M + NH4+):
905.2955.
Found
3.4. Phenyl(4-O-acetyl-2,6-di-O-benzoyl-3-deoxy-b-D-
xylo-hexopyranosyl)-(1!4)-[(2,3,4-tri-O-benzyl-a-L-
fucopyranosyl-(1!3)]-6-O-benzyl-2-deoxy-2-phthalim-
ido-1-thio-b-D-glucopyranoside 8
A mixture of 6 (1 g, 1.12 mmol, 1 equiv) and 7 (1.34 g,
2.81 mmol, 2.5 equiv), 4 A powdered molecular sieves
˚
(7 g) and dry toluene (36 mL) was stirred at room
temperature for 30 min and then cooled to À25 °C
under argon. NIS (518 mg, 2.3 equiv) and then TfOH
(20.5 lL, 0.23 equiv) were added. The reaction mixture
was neutralized (Et3N) after 1 h, diluted with dichloro-
methane, filtered through Celite, washed with aqueous
thiosulfate, water, brine, dried over MgSO4 and
concentrated. The residue was eluted from a column
of silica gel with (toluene–ethyl acetate 9:1) to give 8
(62%): Rf 0.62 (cyclohexane–ethyl acetate 3:2);
1
3.3. Phenyl(4-O-acetyl-2,6-di-O-benzoyl-3-deoxy-b-D-
xylo-hexopyranosyl)-(1!4)-6-O-benzyl-2-deoxy-2-phthal-
imido-1-thio-b-D-glucopyranoside 6
[a]D = +3.3 (c 1.0, chloroform); H NMR (400 MHz,
CDCl3): d 8.15–7.07 (m, 39H, arom), 5.48 (d, 1H,
J1,2 = 10.6 Hz, H-1c), 5.14 (ddd, 1H, J1,2 = 8.4 Hz,
0
J2,3 = 5.1 Hz, J2;3 ¼ 11.8 Hz, H-2d), 5.11 (m, 1H,
A solution of 5 (1.4 g, 2.84 mmol) and 4 (2.38 g,
H-4d), 4.93 (d, 1H, H-1d), 4.91 (d, 1H, J = 3.7 Hz,
H-1e), 4.90, 4.67 (2d, 2H, J = 11.8 Hz, PhCH2), 4.85,
4.26 mmol, 1.5 equiv) in 51 mL of dry CH2Cl2 was
˚
stirred with 5.5 g of ground molecular sieves 4 A
451 (2d, 2H, J = 12.0 Hz, PhCH2), 4.84 (q, 1H, J4,5
1 Hz, J5,6 = 6.4 Hz, H-5e), 4.78 (dd, 1H, J2,3
<
=
for 40 min at room temperature under an argon atmo-
sphere. Trimethylsilyl triflate (773.2 lL, 4.26 mmol,
1.5 equiv) was added at 0 °C, and stirring continued
for an additional hour. The mixture was filtered through
Celite and the solids then washed with CH2Cl2. The fil-
trate was washed with a saturated NaHCO3 solution,
then with water, dried over MgSO4 and concentrated.
The residue was eluted from a column of silica gel with
(toluene–ethyl acetate 9:1) to give 6 (75%): Rf 0.4 (tolu-
ene–ethyl acetate 4:1); [a]D = +17.4 (c 1.0, chloroform);
1H NMR (400 MHz, CDCl3): d 8.11–7.20 (m, 24H,
arom), 5.63 (d, 1H, J1,2 = 10.5 Hz, H-1c), 5.36 (m, 1H,
H-2d), 5.23 (m, 1H, H-4d), 4.82 (d, 1H, J = 8.1 Hz,
10.0 Hz, J3,4 = 9.3 Hz, H-3c), 4.69, 4.65 (2d, 2H,
J = 11.9 Hz, PhCH2), 4.54 (dd, 1H, H-2c), 4.40 (dd,
0
1H, J5,6 = 3.9 Hz, J6;6 ¼ 11.0 Hz, H-6d), 4.24 (dd,
0
1H, J4,5 = 9.2 Hz, H-4c), 4.19 (dd, 1H, J5;6 ¼ 6.9 Hz,
H-60d), 4.07 (dd, 1H, J2,3 = 10.3 Hz, J3,4 = 2.5 Hz,
0
H-3e), 4.01 (dd, 1H, J5,6 = 2.9 Hz, J6;6 ¼ 11.3 Hz,
H-6c), 3.88 (dd, 1H, H-2e), 3.82–3.78 (m, 2H, H-
5d, H-60c), 3.72 (dd, 1H, H-4e), 3.56 (dd, 1H, H-5c),
0
2.42 (ddd, 1H, J3;3 ¼ 14.0 Hz, J3,4 = 3.0 Hz, H-3d),
0
1.90 (s, 3H, CH3), 1.66 (ddd, 1H, J3 ;4 ¼ 3.2 Hz,
H-30d), 1.29 (d, 3H, H-6e); 13C NMR (100.6 MHz,
CDCl3): d 169.71 (C@O, Ac), 165.85, 164.84 (2C@O,
Bz), 138.93, 138.63, 138.18, 137.98, 132.46, 129.47
(C-arom), 134.08, 133.39, 133.27, 132.23, 129.75,
129.51, 128.74, 128.70, 128.50, 128.48, 128.23, 128.18,
128.07, 127.86, 127.62, 127.41, 127.03, 126.78 (CH
0
H-1d), 4.66 (dd, 1H, J5,6 = 3.3 Hz, J6;6 ¼ 11.6 Hz, H-
6d), 4.65 (d, 1H, J = 1 Hz, exch. D2O, OH-3c), 4.59
(ddd, 1H, J2,3 = 10.3 Hz, J3,4 = 8.2 Hz, H-3c), 4.39
(dd, 1H, H-2c), 4.33, 4.27 (2d, 2H, J = 12 Hz, PhCH2),

3028
C. Gourmala et al. / Tetrahedron: Asymmetry 16 (2005) 3024–3029
arom), 100.89 (C-1d), 97.80 (C-1e), 84.32 (C-1c), 79.70
(C-3e), 79.33 (C-4e), 77.53 (C-5c), 74.99 (C-4c), 74.34
(C-2e), 73.91 (C-3c), 73.67 (C-5d), 74.13, 73.54, 72.98,
72.43 (4PhCH2), 67.95 (C-2d), 67.87 (C-6c), 66.98
(C-4d), 66.45 (C5-e), 61.45 (C-6d), 55.51 (C-2c), 32.98
(C-3d), 20.84 (CH3), 16.82 (C-6e). HRMS (FAB) Calcd
for C76H73NO17SNa (M+Na+): 1326.4497. Found
1326.4515.
for C122H131NO28SiNa (M+Na+) 2109.8525. Found
2108.8557.
3.6. 2-(Trimethylsilyl)ethyl(3-deoxy-b-D-xylo-hexopyr-
anosyl)-(1!4)-[(2,3,4-tri-O-benzyl-a-L-fucopyranosyl-
(1!3)]-6-O-benzyl-2-deoxy-2-acetamido-b-D-glucopyr-
anoside-(1!3)-(2,6-di-O-benzyl-b-D-galactopyranosyl)-
(1!4)-2,3,6-tri-O-benzyl-b-D-glucopyranoside 11
To a solution of compound 10 (480 mg, 0.23 mmol) in
68 mL of ethanol, were added 4 mL of hydrazine mono-
hydrate and 4 mL of water. The mixture was refluxed at
80 °C for 14 h. After concentration, the residue was co-
evaporated with ethyl acetate and dried over P2O5. The
residue was then dissolved in 20 mL of methanol–
dichloromethane (1:1), to which 2 mL of acetic anhy-
dride was introduced. The mixture was stirred at
room temperature overnight. After concentration, the
residue was dried in vacuo, and used directly for the next
step.
3.5. 2-(Trimethylsilyl)ethyl(4-O-acetyl-2,6-di-O-benzoyl-
3-deoxy-b-D-xylo-hexopyranosyl)-(1!4)-[(2,3,4-tri-O-
benzyl-a-L-fucopyranosyl-(1!3)]-6-O-benzyl-2-deoxy-2-
phtalimido-b-D-glucopyranoside-(1!3)-(2,6-di-O-benzyl-
b-D-galactopyranosyl)-(1!4)-2,3,6-tri-O-benzyl-b-D-
glucopyranoside 10
A mixture of 8 (153 mg, 0.117 mmol), 9 (104 mg,
˚
0.117 mmol), 4 A powdered molecular sieves (0.7 g)
and CH2Cl2 (7.3 mL) was stirred at room temperature
for 30 min. NIS (2 equiv, 52.7 mg, 0.234 mmol) was
added at room temperature. The reaction mixture was
cooled at À30 °C. Triflic acid (0.035 mmol, 4 lL) was
added. The reaction mixture was stirred at À30 °C for
1 h, neutralized (Et3N), filtered through Celite, washed
with aqueous thiosulfate, water, brine, dried over
MgSO4 and concentrated. The residue was flash chro-
matographed (toluene–ethyl acetate 6:1) to give 10
(70%) as an amorphous powder: Rf 0.33 (toluene–ethyl
3.7. 2-(Trimethylsilyl)ethyl(3-deoxy-b-D-xylo-hexo-
pyranosyl)-(1!4)-[(a-L-fucopyranosyl-(1!3)]-2-acet-
amido-2-deoxy-b-D-glucopyranoside-(1!3)-(b-D-galacto-
pyranosyl)-(1!4)-2,-b-D-glucopyranoside 1
A solution of 11 (104 mg) in methanol (10 mL) was
reacted over Pd/C (10%, 100 mg) under H2 (160 kPa)
for 24 h at 25 °C, filtered and evaporated. The residue
was purified on a Sephadex column (G25-150) using
water as eluant. Compound 1 was obtained as a white
amorphous solid (99%): Rf 0.25 (isopropanol–ethyl ace-
tate–water 3:3:1); [a]D = À106 (c 0.4, CHCl3–CH3OH 1/
1); 1H NMR (400 MHz, D2O): d 5.13 (d, 1H,
J = 3.97 Hz, H-1e), 4.88 (m, 1H, H-5e), 4.87 (m, 1H),
4.72 (d, 1H, J = 8.2 Hz, H-1), 4.50 (d, 1H, J = 8.1 Hz,
H-1), 4.47 (d, 1H, J = 8.5 Hz, H-1), 4.44 (d, 1H,
J = 8.1 Hz, H-1), 4.16 (d, 1H, J = 3.3 Hz), 4.07–3.95
(m, 6H), 3.92–3.85 (m, 3H), 3.81–3.62 (m, 16H), 3.61–
3.55 (m, 4H), 3.28 (m, 1H, H-2), 2.18 (ddd, 1H,
1
acetate 6:1); [a]D = +6.2 (c 1.0, chloroform); H NMR
(400 MHz, CDCl3): d 8.05–7.18 (m, 59H, arom), 5.30
(d, 1H, J1,2 = 8.4 Hz, H-1c); 5.14 (m, 2H, H-4d, H-2d);
4.95, 4.70 (2d, 2H, J = 10.5 Hz, PhCH2), 4.91 (d, 1H,
J1,2 = 8.2 Hz, H-1d), 4.87 (d, 1H, J1,2 = 3.7 Hz, H-1e),
4.80 (m, 1H, H-5e), 4.77 (dd, 1H, J2,3 = 10.4 Hz,
J3,4 = 8.7 Hz, H-3c), 4.28 (d, 1H, J1,2 = 7.6 Hz, H-1a),
4.26 (d, 1H, J1,2 = 8.2 Hz, H-1b), 4.50 (dd, 1H, H-2c),
4.49 (d, 1H, J = 12.1 Hz, PhCH2), 4.79, 4.45 (2d, 2H,
J = 12.0 Hz, PhCH2), 4.46, 4.23 (2d, 2H, J = 11.9 Hz,
PhCH2), 4.20 (dd, 1H, J4,5 = 9.2 Hz, H-4c), 4.29–4.14
(m, 4H, PhCH2), 4.04 (m, 1H, H-5c), 4.05–3.92 (m,
3H), 3.73–3.67 (m, 3H), 3.59–3.44 (m, 4H), 3.42–3.30
(m, 6H), 3.00 (m, 1H), 2.44 (ddd, 1H, J2,3 = 5.0 Hz,
0
J2,3 = 5.0 Hz, J3;3 ¼ 14.1 Hz, J3,4 = 3.1 Hz, H-3d), 2.03
0
(s, 3H, NHAc), 1.72 (ddd, 1H, J2;3 ¼ 11.7 Hz,
J3 ;4 ¼ 3.0 Hz, H-30d), 1.17 (d, 3H, J = 6.6 Hz, H-6e),
0
0
J3;3 ¼ 14.4 Hz, J3,4 = 3.1 Hz, H-3d), 1.91 (s, 3H, CH3),
1.67 (ddd, 1H, J2;3 ¼ 11.6 Hz, J3 ;4 ¼ 3.2 Hz, H-30d),
1.29 (d, 3H, J5,6 = 6.4 Hz, H-6e), 1.06–0.95 (m, 2H,
CH2Si), 0.03 (s, 9H, Si(CH3)3); 13C NMR (100.6 MHz,
CDCl3): d 169.73 (C@O, Ac), 165.88, 164.83 (2C@O,
Bz), 139.00, 138.91, 138.74, 138.62, 138.47, 138.27,
138.19, 137.69, 131.13, 129.52 (aromatic C), 133.73,
133.39, 133.33, 129.77, 129.50, 128.71, 128.58, 128.54,
128.34, 128.24, 128.21, 128.18, 128.17, 128.07, 128.05,
128.00, 127.94, 127.84, 127.73, 127.62, 127.53, 127.43,
127.42, 127.35, 127.14, 127.04, 127.00, 126.77,
126.52, 126.21 (aromatic CH), 102.97 (C-1b), 101.93
(C-1a), 100.93 (C-1d), 98.89 (C-1c), 97.69 (C-1e), 83.14,
82.78, 81.82, 79.58, 77.98, 77.54, 75.88, 75.17, 74.87,
74.58, 73.78, 72.75, 72.53, 68.01, 67.50, 66.97, 66.45,
(CH), 75.33, 74.85, 74.14, 74.01, 73.75, 73.27, 72.86,
72.42, 68.40 (PhCH2), 68.10 (OCH2Si), 67.96,
67.77, 67.18 (C-6a, C-6b, C-6c), 61.52 (C-6d), 56.25
(C-2c), 33 (C-3d), 20.84 (OAc), 18.37 (CH2Si),
16.84 (C-6e), À1.47 (Si(CH3)3). HRMS (FAB) Calcd
1.02 (2dt, 2H, Jgem = 12.9 Hz, Jvic = 5.4 Hz, CH2Si),
0.028 (s, 9H, Si(CH3)3); 13C NMR (100.6 MHz, D2O):
d 175.08 (C@O, NHAc), 103.91, 103.3, 102.92, 101.73,
99.02 (C-1a, C-1b, C-1c, C-1d, C-1e), 82.44, 78.64,
78.43, 75.52, 75.23, 75.11, 74.89, 73.18, 73.07, 72.36,
70.33, 69.57, 68.67, 68.06, 67.00, 66.10, 65.83 (CH),
68.81 (OCH2Si), 62.08, 61.32, 60.41, 60.01 (C-6a, C-
6b, C-6c, C-6d), 56.35 (C-2c), 36.94 (C-3d), 22.61
(CH3), 17.92 (CH2Si), 15.68 (C-6e), À2.17 (Si(CH3)3).
HRMS (FAB) Calcd for C37H67NO24SiNa (M+Na+)
960.3720 found. Anal. Calcd for C37H67NO24Si
(938.01): C, 47.38; H, 7.20; N, 1.49. Found C, 47.43;
H, 7.22; N, 1.51.
0
0
Acknowledgements
Financial support from the CNRS and the ENS is grate-
fully acknowledged.

C. Gourmala et al. / Tetrahedron: Asymmetry 16 (2005) 3024–3029
3029
7. Pincet, F.; Le Bouar, T.; Zhang, Y.; Esnault, J.; Mallet,
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