Regio- and stereocontrolled synthesis of 2d-deoxy Lewisx pentasaccharide

Article abstract of DOI:10.1002/ejoc.201101062

The total synthesis of 2d-deoxy Lewis^x pentasaccharide is described. Ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α,β-D- galactopyranoside was condensed with a diol of glucosamine to regio- and stereoselectively give the disaccharide, the C-2′ po

Full text of DOI:10.1002/ejoc.201101062

FULL PAPER
DOI: 10.1002/ejoc.201101062
Regio- and Stereocontrolled Synthesis of 2d-Deoxy Lewisx Pentasaccharide
Yanyan Zhang,[a,b] Dengxiang Dong,[a,b] Huanhuan Qu,[a] Matthieu Sollogoub,[a] and
Yongmin Zhang*[a]
Keywords: Total synthesis / Carbohydrates / Glycosylation / Oligosaccharides / Regioselectivity / Diastereoselectivity
The total synthesis of 2d-deoxy Lewisx pentasaccharide is
described. Ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α,β-
galactopyranoside was condensed with a diol of glucosamine
to regio- and stereoselectively give the disaccharide, the C-
2Ј position was then reduced after stereoselective fucosyl-
ation to afford a Lewisx trisaccharide analogue. Regioselec-
tive glycosylation of a known lactoside diol with this trisac-
charide provided a pentasaccharide that, after deprotection,
gave the target pentasaccharide.
D-
orientational freedom of the Lex group, the natural lipid
showed a restricted orientation of the Lex group. The ad-
hesion induced by Lex–Lex interactions was thereby con-
siderably enhanced, indicating that the relative orientation
of the two Lex groups is a dominant factor in Lex–Lex re-
cognition.[16] In another experiment, the Lex trisaccharide
determinant in the headgroup was replaced by its isomer
Lea trisaccharide, in which the galactose and fucose groups
are permutated relative to Lex on one vesicle surface. The
adhesion energy observed for the Lex–Lea pair was very
weak, confirming the homotypic characteristics of this type
of carbohydrate–carbohydrate interaction.[16]
Introduction
Carbohydrates play an important role in many biological
occurrences including recognition, adhesion and communi-
cation between cells, inflammation, and bacterial and viral
infections.[1,2] A variety of these processes are known to in-
volve not only carbohydrate–protein interactions,[3,4] but
also interactions between carbohydrate molecules.[5] A typi-
cal example is the report of Hakomori, who proposed that
carbohydrate–carbohydrate interaction is responsible for
the initial step of cell adhesion.[6] One of the structures in-
volved in this novel mechanism is the Lewisx (Lex) trisac-
charide determinant (Galβ1Ǟ4[Fucα1Ǟ3]GlcNAcβ1). The
interaction between Lex and Lex was found to be homo-
typic, and mediated by the presence of divalent cations such
Based on our previous studies on Lex–Lex interac-
tions,[9b,9f,11a,11b,16] we became interested in exploring the
molecular mechanism involved in this new type of carbo-
hydrate–carbohydrate interaction. To gain insight into the
functions of the different hydroxyl groups on the Lex trisac-
charide molecule, we planned to generate a series of penta-
saccharides in which one of the eight hydroxyl groups was
replaced by a hydrogen atom, and to quantify the adhesion
energy induced by interactions of these derivatives. Having
synthesized the 3d-deoxy, 4d-deoxy, and 6d-deoxy Lewisx
pentasaccharides,[17,18,19] herein, we would like to report on
the first total synthesis of 2d-deoxy Lewisx pentasaccharide
(1), which could be a useful tool for a mechanistic study of
carbohydrate–carbohydrate interactions (Scheme 1).
as Ca2+ [7,8]
.
Recently, the Lex–Lex interaction has been studied more
extensively by using a variety of techniques including nu-
clear magnetic resonance (NMR) spectroscopy,[9] mass
spectrometry (MS),[10] vesicle adhesion,[11] atomic force mi-
croscopy (AFM),[12] and surface plasmon resonance (SPR)
spectroscopy.[13] Rat basophilic leukaemia cells pre-incu-
bated with purified Lex-containing glycosphingolipids have
been used as a model.[14] Another model system termed
“Glycosylated Foldamer” was developed for the study of
carbohydrate–carbohydrate interactions in terms of individ-
ual carbohydrate motifs.[15] By using a vesicle micromanipu-
lation approach with chemically synthesized natural Lex
pentasaccharide glycosphingolipid, we have demonstrated
that, in contrast to glyconeolipids,[11] which allow strong
[a] Université Pierre et Marie Curie-Paris 6, Institut Parisien de
Chimie Moléculaire, UMR 7201 CNRS,
4 place Jussieu, 75005 Paris, France
Fax: +33-1-44275504
E-mail: yongmin.zhang@upmc.fr
Scheme 1. Structure of 2d-deoxy Lewisx pentasaccharide.
[b] Guiyang College of Traditional Chinese Medicine,
50 Shidong Road, 550002 Guiyang, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101062.
Among the various deoxy sugars, 2-deoxy derivatives
have been found to be significant as integral components of
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Y. Zhang et al.
FULL PAPER
many natural products.[20] These compounds are interesting presence of the 3-OH in disaccharide 5 confirmed that the
not only because of their biological profiles but also be- position of the new glycosidic linkage in 5 was at 4-OH of
cause of the synthetic challenges they present. The main diol 4. Its configuration was determined to be the desired β
challenge in the synthesis of 1 is the construction of the anomer on the basis of the 1d-H, 2d-H coupling constant
glucopyranosyl 2-deoxy-β-galactopyranosidic linkage. We (J1d,2d = 7.9 Hz). Glycosyl donor 3β was also prepared by
therefore adopted an indirect synthetic method to access Thijssen et al. from 3,4,6-tri-O-benzyl-1,2-O-(1-thioethylid-
the 2-deoxy-β-disaccharide that entailed the use of a donor ene)-α-d-galactopyranose by reaction with trimethylsilyl
containing a participating group at C-2 to insure the desired triflate.[24]
β-glycosidic linkage; the C-2 position was then reduced af-
For construction of the trisaccharide, disaccharide 5 was
ter fucosylation.[21] In this approach, the desired β1Ǟ4 fucosylated with 2,3,4-tri-O-benzyl-l-fucosyl fluoride (6)
[19,25,26]
linked disaccharide was obtained in high yield.
in toluene/dichloromethane using silver triflate and
stannous chloride as promoters. Compound 7 was obtained
in 71% yield (Scheme 4). The configuration of the newly
introduced glycosidic linkage was determined to be α on
the basis of the low value of the Fuc 1-H, 2-H coupling
constant (J1e,2e = 3.9 Hz).
Results and Discussion
For synthesis of the target 1, the known 1,2-di-O-acetyl-
3,4,6-tri-O-benzyl-d-galactopyranose (2; α/β, 1:1)[22] was
first used to react with previously prepared diol 4[23] in the
presence of trimethylsilyl trifluoromethanesulfonate
(TMSOTf) to regioselectively give the β 1Ǟ4 linked disac-
charide 5 (Scheme 3), however, the yield of the reaction was
not satisfactory (47%), and some starting materials were
recovered. Compound 2 was then converted into the thioe-
thyl donor 3 (Scheme 2), which was coupled with 4 in tolu-
ene using N-iodosuccinimide (NIS)-TfOH as promoters
without affecting the SPh group of the acceptor 4. The de-
sired disaccharide 5 was regio- and stereoselectively ob-
tained in 73% yield (Scheme 3). Being more nucleophilic,
the SEt group displays a stronger reactivity than the SPh
group as a glycosylation donor, such selective behaviour has
been observed in our previous work.[17] The use of dichloro-
methane as solvent gave a lower yield.
Compound 8 was obtained by deacetylation with
Mg(OMe)2 solution[27] of trisaccharide 7. With compound
8 in hand, we first tried to realize the deoxygenation of
galactose at the 2-position by reaction with phenyl chloro-
thionocarbonate. However, we failed to introduce the phen-
oxythiocarbonyl at the desired position, with no reaction at
all being observed, probably due to the steric hindrance of
the phenyl chlorothionocarbonate. Alcohol 8 was then con-
verted into the corresponding trisaccharide xanthate 9 by
treatment with sodium hydride in tetrahydrofuran, carbon
disulfide, and a catalytic amount of imidazole, followed by
reaction with methyl iodide.[21] The radical reduction of the
xanthate by tributylstannane in the presence of azobisiso-
butyronitrile (AIBN) gave the deoxy-derivative 10 in 87%
yield (Scheme 4).
The glycosylation of diol 11[28] with donor 10 was pro-
moted by NIS and triflic acid to regio- and stereoselectively
afford the desired pentasaccharide 12 in 86% yield
(Scheme 5).
The configuration of the newly introduced linkage was
determined to be β on the basis of the GlcN 1-H, 2-H cou-
pling constant (J1c,2c = 8.4 Hz). The regioselectivity was
Scheme 2. Synthesis of galactose building block 3.
1
confirmed from the H NMR spectrum of 12Ј – obtained
The 1H NMR spectrum of 5 revealed the presence of 3c- from 12 by acetylation – which revealed a deshielded signal
H of the glucosamine residue at δ = 4.45 ppm (dd, J2c,3c
=
for 4b-H at δ = 5.45 ppm (d, J3b,4b = 3.5 Hz). The presence
10.4, J3c,4c = 7.8 Hz), indicating the position of the newly of 4b-OH in pentasaccharide 12 confirmed that the position
formed glycosidic linkage in the disaccharide 5 to be at 4- of the new glycosidic linkage in 12 was at 3-OH of the diol
OH of acceptor 4. This regioselectivity was further con- 11.
1
firmed from the H NMR spectrum of 5Ј – obtained from
Treatment of pentasaccharide 12 with hydrazine in boil-
5 by acetylation – which revealed a deshielded signal for 3c- ing ethanol, followed by selective N-acetylation, afforded
H at δ = 5.70 ppm (dd, J2c,3c = 10.1, J3c,4c = 8.9 Hz). The compound 13 in 84% overall yield from 12. Catalytic hy-
Scheme 3. Synthesis of lactosamine building block 5.
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Synthesis of 2d-Deoxy Lewisx Pentasaccharide
Scheme 4. Synthesis of 2d-deoxy Lewisx trisaccharide 10.
Scheme 5. Synthesis of 2d-deoxy Lewisx pentasaccharide 1.
drogenolysis of 13 in methanol, followed by purification, OH and 4b-OH groups. After the synthesis of the 3d-deoxy,
provided the pentasaccharide 1 as a white amorphous solid 4d-deoxy, and 6d-deoxy Lewisx pentasaccharides,[17–19] we
in 90% yield (Scheme 5).
finally achieved the synthesis of the last member of this
Compound 1 was fully characterized by 1H and 13C family, the 2d-deoxy Lewisx pentasaccharide. These com-
NMR analyses, as well as by HRMS.
pounds will be used as useful tools for the study of carbo-
hydrate–carbohydrate interactions.
Conclusions
Experimental Section
Our strategy allows the facile and convergent total syn-
thesis of 2d-deoxy Lewisx pentasaccharide in good yield.
We adopted an indirect synthetic method to construct the
General Conditions: All chemicals were purchased as reagent grade
and used without further purification. Dichloromethane (CH2Cl2)
2-deoxy-β-disaccharide that entailed the use of a donor was freshly distilled from P2O5. Tetrahydrofuran (THF) was dis-
tilled from sodium/benzophenone and toluene was distilled from
sodium. H NMR spectra were recorded with a Bruker DRX 400
containing a participation group at C-2 to insure the re-
gioselectivity of β-glycosidic linkage formation. The 2-posi-
tion of this participation group was then reduced after fuco-
sylation, giving the 2Ј-deoxy derivative in high yield. Prepa-
ration of trisaccharide 7 by fucosylation of 5 with the
powerful fluoride donor 6 gave the desired trisaccharide 7
in high yield. Construction of the pentasaccharide 12 was
successfully achieved in very good yield by a highly regio-
and stereoselective glycosylation of diol 11 with donor 10,
1
spectrometer at ambient temperature. Assignments were aided by
COSY experiments. 13C NMR spectra were recorded at 100.6 MHz
with a Bruker DRX 400 spectrometer for solutions in CDCl3, D2O.
High-resolution mass spectra (HRMS) were recorded with a
Bruker micrOTOF spectrometer in electrospray ionization (ESI)
mode. Optical rotations were measured at 589 nm (Na line) at
20 °C with a Perkin–Elmer Model 343 digital polarimeter, using a
10 cm, 1 mL cell. Reactions were monitored by thin-layer
taking advantage of the activity difference between the 3b- chromatography (TLC) on a precoated plate of silica gel 60 F254
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Y. Zhang et al.
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(Merck, 0.2 mm) and detection by charring with sulfuric acid. Flash
column chromatography was performed on silica gel 60 (230–
400 mesh, Merck), Sephadex G25 and Sephadex LH20 (Sigma).
3.45–3.38 (m, 2 H, 3d-H, 6-H), 1.91 (s, 3 H, Ac) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 169.40 (MeC=O), 168.15, 167.71 (2ϫ
C=O, NPhth), 138.55, 138.19, 137.84, 137.48, 132.37, 132.03,
131.94 (Ar-C), 134.11, 132.70, 128.94–127.61 (Ar-CH), 101.92 (C-
1d), 83.55 (C-1c), 81.73 (C-4c), 80.35 (C-3d), 78.47 (C-5c), 74.62,
73.70, 73.66, 72.33 (4ϫ PhCH2), 73.95 (C-5d), 72.37 (C-4d), 71.31
(C-2d), 71.01 (C-3c), 68.60, 68.56 (2C-6), 55.26 (C-2c), 21.11
(CH3CO) ppm. HRMS (ESI): calcd. for C56H55NO12SNa [M +
Na]+ 988.3337; found 988.3354.
Ethyl 2-O-Acetyl-3,4,6-tri-O-benzyl-1-thio-α,β-D-galactopyranoside
(3): A solution of 2 (0.5 g, 0.94 mmol) in dry CH2Cl2 (16 mL) con-
taining powdered molecular sieves (0.5 g, 4 Å) was cooled to 0 °C.
Thioethanol (84 μL, 1.12 mmol) was added dropwise followed by
addition of BF3·Et2O (0.36 mL, 2.84 mmol). The mixture was
stirred at room temperature for 14 h, and then neutralized with
saturated aqueous NaHCO3 solution, washed with water, dried
with MgSO4 then concentrated. The residue was purified by flash
column chromatography (Cy/EtOAc = 10:1) to give product 3 as a
mixture of α/β isomers (0.46 g, 92%, α/β, 1:5). Data for the α-an-
omer: Rf = 0.50 (Cy/EtOAc = 4:1). [α]2D0 = +114 (c = 1.0; CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.35–7.25 (m, 15 H, Ar-H), 5.72
(d, J = 5.6 Hz, 1 H, 1-H), 5.43 (q, J = 5.6, 10.3 Hz, 1 H, 2-H), 4.93
(d, J = 11.5 Hz, 1 H, PhCHH), 4.68 (s, 2 H, PhCH2), 4.57 (d, J =
11.5 Hz, 1 H, PhCHH), 4.48, 4.42 (2ϫ d, J = 11.8 Hz, 2 H,
PhCH2), 4.30 (t, J = 6.4 Hz, 1 H, 5-H), 3.98–3.97 (m, 1 H, 4-H),
3.81 (dd, J = 10.3, 2.8 Hz, 1 H, 3-H), 3.63–3.54 (m, 2 H, 6-H),
2.59–2.46 (m, 2 H, CH2CH3), 2.02 (s, 3 H, Ac), 1.23 (t, J = 7.4 Hz,
3 H, CH2CH3) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 170.34
(MeC=O), 138.58, 138.39, 138.12 (Ar-C), 128.56, 128.53, 128.39,
128.29, 127.86, 127.84, 127.74, 127.57 (Ar-CH), 82.14 (C-1), 77.70
(C-3), 74.68 (C-4), 74.93, 73.61, 73.04 (3ϫ PhCH2), 71.32 (C-2),
69.75 (C-5), 68.92 (C-6), 24.03 (CH2CH3), 21.18 (CH3CO), 14.83
(CH2CH3) ppm. HRMS (ESI): calcd. for C31H36O6SNa
[M + Na]+ 559.2125; found 559.2148. Data for the β-anomer:
[α]D20 = –1 (c = 1.0; CHCl3) {ref. [α]D20 = –1 (c = 1.0; CHCl3)}. The
1H NMR spectroscopic data of the compound were in agreement
Phenyl (2-O-Acetyl-3,4,6-tri-O-benzyl-β-
(1Ǟ4)-3-O-acetyl-6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β-
D
-galactopyranosyl)-
-glu-
D
copyranoside (5Ј): A solution of 5 (40 mg) in pyridine (1 mL) and
acetic anhydride (0.5 mL) was stirred at room temperature for 14 h
and then concentrated, co-evaporated with toluene and dried.
Compound 5Ј was obtained in quantitative yield (41 mg). Rf = 0.47
(Cy/EtOAc = 2:1). [α]2D0 = +25 (c = 1.0; CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 7.86–7.18 (m, 29 H, Ar-H), 5.70 (dd, J =
10.1, 8.9 Hz, 1 H, 3c-H), 5.69 (d, J = 10.6 Hz, 1 H, 1c-H), 5.20
(dd, J = 7.9, 10.0 Hz, 1 H, 2d-H), 4.89 (d, J = 11.6 Hz, 1 H,
PhCHH), 4.69, 4.63 (2ϫ d, J = 11.9 Hz, 2 H, PhCHH), 4.53–4.37
(m, 5 H, PhCH2), 4.41 (d, J = 7.9 Hz, 1 H, 1d-H), 4.25 (t, 1 H, J
= 10.4 Hz, 2c-H), 3.95 (t, J = 9.1, 9.8 Hz, 1 H, 4c-H), 3.92–3.91
(m, 1 H, 4d-H), 3.79–3.78 (m, 2 H, 2ϫ 6-H), 3.70 (dt, J = 10.0,
2.4 Hz, 1 H, 5c-H), 3.58–3.46 (m, 2 H, 2ϫ 6-H), 3.40–3.38 (m, 1
H, 5d-H), 3.36 (dd, 1 H, J = 10.1, 2.8 Hz, 3d-H), 1.95, 1.73 (2ϫ s,
6 H, 2ϫ Ac) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 170.09,
169.25 (2ϫ MeC=O), 167.81, 167.47 (2ϫ C=O, NPhth), 138.66,
138.35, 138.08, 137.84, 131.93, 131.71, 131.46 (Ar-C), 134.43,
134.14, 133.09, 128.98–127.47, 123.86, 123.56 (Ar-CH), 100.93 (C-
1d), 83.11 (C-1c), 80.47 (C-3d), 79.18 (C-5c), 75.21 (C-4c), 74.51,
73.67, 73.59, 71.82 (4ϫ PhCH2), 73.33 (C-5d), 72.53 (C-3c), 72.34
(C-4d), 71.85 (C-2d), 68.10, 68.06 (2C-6), 54.08 (C-2c), 21.14, 20.62
(2 ϫ CH3CO) ppm. HRMS (ESI): calcd. for C58H57NO13SNa
[M + Na]+ 1030.3443; found 1030.3463.
with those reported in literature.[24]
.
Phenyl (2-O-Acetyl-3,4,6-tri-O-benzyl-β-
D
-galactopyranosyl)-
(1Ǟ4)-6-O-benzyl-2-deoxy-2-phthalimido-1-thio-β- -gluco-
D
pyranoside (5). Method A (2 + 4): A mixture of 2 (50 mg,
0.09 mmol), 4 (59 mg, 0.12 mmol), and 4 Å powdered molecular
sieves was stirred in dry CH2Cl2 (2 mL) for 30 min at room tem-
perature under nitrogen, then cooled to 0 °C. TMSOTf (17 μL,
0.09 mmol) was added and the mixture was stirred at 0 °C for 2 h,
filtered through Celite, washed with saturated NaHCO3 solution
and brine, dried with MgSO4, filtered, and concentrated. After pu-
rification by flash column chromatography (toluene/ethyl acetate =
8:1), compound 5 was obtained (42 mg, 47%) as a white amorph-
ous solid.
Phenyl (2-O-Acetyl-3,4,6-tri-O-benzyl-β-
(1Ǟ4)-[2,3,4-tri-O-benzyl-α- -fucopyranosyl-(1Ǟ3)]-6-O-benzyl-
2-deoxy-2-phthalimido-1-thio-β- -glucopyranoside (7): A solution of
D-galactopyranosyl)-
L
D
5 (0.53 g, 0.55 mmol) and 6 (0.48 g, 1.10 mmol) in dry CH2Cl2
(20 mL) and dry toluene (4 mL) was stirred with 4 Å powdered
molecular sieves for 30 min at room temperature under nitrogen. A
mixture of stannous chloride (0.18 g, 0.96 mmol) and silver triflate
(0.25 g, 0.96 mmol) was added at –15 °C and the reaction mixture
was stirred for 2 h at –15 °C, then filtered through Celite and
washed with CH2Cl2. The filtrate was washed with saturated
NaHCO3 solution, then with water, dried with MgSO4 and concen-
trated. After purification by flash column chromatography (Cy/
Method B (3 + 4): A mixture of 3 (0.15 g, 0.28 mmol), 4 (0.18 g,
0.37 mmol), and powdered molecular sieves (4 Å) was stirred in dry
toluene (6 mL) for 30 min at room temperature under nitrogen, EtOAc = 6:1), compound 7 was obtained (0.54 g, 71%) as a white
then cooled to –30 °C. NIS (76 mg, 0.34 mmol) and TfOH (5 μL,
0.056 mmol) were added and the mixture was stirred at –30 °C for
2 h, then neutralized with Et3N, diluted with dichloromethane, fil-
tered through Celite, washed with aqueous sodium thiosulfate, and
brine, dried with MgSO4, filtered, and concentrated. After purifica-
tion by flash column chromatography (toluene/ethyl acetate = 8:1),
compound 5 was obtained (0.20 g, 73%) as a white amorphous
solid. Rf = 0.42 (Cy/EtOAc = 2:1). [α]2D0 = +21 (c = 1.0; CHCl3).
amorphous solid. Rf = 0.30 (Cy/EtOAc = 3:1). [α]2D0 = –11 (c = 1.0;
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.80–6.94 (m, 44 H, Ar-
H), 5.47 (d, J = 10.5 Hz, 1 H, 1c-H), 5.27 (dd, J = 8.2, 10.0 Hz, 1
H, 2d-H), 4.87 (d, J = 10.6 Hz, 1 H, PhCHH), 4.78–4.71 (m, 3 H,
3c-H, PhCHH), 4.68 (d, J = 3.9 Hz, 1 H, 1e-H), 4.63–4.60 (m, 1
H, 5e-H), 4.60 (d, J = 8.2 Hz, 1 H, 1d-H), 4.55–4.51 (m, 2 H,
PhCH2), 4.49 (d, J = 10.2 Hz, 1 H, 2c-H), 4.46–4.32 (m, 7 H,
PhCH2), 4.21 (d, J = 12.3 Hz, 1 H, PhCH2), 4.12 (t, J = 9.3 Hz, 1
1H NMR (400 MHz, CDCl3): δ = 7.88–7.16 (m, 29 H, Ar-H), 5.58 H, 4c-H), 4.01–4.00 (m, 1 H, 4d-H), 3.90–3.81 (m, 4 H, 3e-H, 6-
(d, J1,2 = 10.6 Hz, 1 H, 1c-H), 5.35 (dd, J = 8.0, 10.0 Hz, 1 H, 2d-
H), 4.88 (d, J = 11.7 Hz, 1 H, PhCHH), 4.65, 4.63 (2ϫd, J =
11.9 Hz, 2 H, PhCHH), 4.52–4.49 (m, 3 H, PhCH2), 4.45 (dd, J =
10.4, 7.8 Hz, 1 H, 3c-H), 4.39 (d, J = 8.0 Hz, 1 H, 1d-H), 4.38 (br.
H, PhCH2), 3.78–3.64 (m, 3 H, 2e-H, 6-H), 3.59–3.56 (m, 1 H, 5c-
H), 3.38–3.33 (m, 2 H, 3d-H, 5d-H), 3.18–3.17 (m, 1 H, 4e-H),
2.03 (s, 3 H, Ac), 1.12 (d, J = 6.5 Hz, 3 H, 6e-H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 169.06 (MeC=O), 139.38, 139.16, 138.80,
s, 1 H, exch. D2O, 3c-OH), 4.34–4.26 (m, 2 H, PhCH2), 4.24 (dd, 138.30, 138.29, 138.10, 137.94, 132.67 (Ar-C), 134.26, 132.43,
J = 10.6, 10.4 Hz, 1 H, 2c-H), 3.85–3.84 (m, 1 H, 4d-H), 3.76–3.63
(m, 4 H, 4c-H, 5c-H, 2ϫ 6-H), 3.56–3.54 (m, 2 H, 5d-H, 6-H),
128.91, 128.86, 128.66, 128.56, 128.52, 128.32, 128.13, 128.02,
127.97, 127.86, 127.83, 127.81, 127.78, 127.74, 127.38, 127.33,
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Synthesis of 2d-Deoxy Lewisx Pentasaccharide
127.24, 127.14, 127.06, 123.86 (Ar-CH), 99.98 (C-1d), 97.30 (C-1e),
(m, 2 H, 4d-H, 6c-H), 3.80 (d, J = 11.2 Hz, 1 H, PhCHH), 3.78–
84.45 (C-1c), 80.93 (C-5d), 79.97 (C-5c), 79.56 (C-3e), 78.60 (C-4e), 3.73 (m, 2 H, 3e-H, 6cЈ-H), 3.67–3.55 (m, 3 H, 2e-H, 2ϫ 6d-H),
75.53, 74.97, 73.52, 73.47, 72.82, 72.10, 72.00 (7ϫ PhCH2), 74.16 3.50–3.48 (m, 1 H, 5c-H), 3.36 (dd, J = 9.6, 2.8 Hz, 1 H, 3d-H),
(C-2e), 74.11 (C-4c), 73.15 (C-4d), 72.92 (C-3d), 72.63 (C-3c), 71.64 3.23–3.19 (m, 1 H, 5d-H), 3.10–3.09 (m, 1 H, 4e-H), 2.57 (s, 3 H,
(C-2d), 68.08 (C-6c), 67.77 (C-6d), 66.77 (C-5e), 55.82 (C-2c), 21.09 SCH3 ), 1.00 (d, J = 6.5 Hz, 3 H, 6e-H) ppm. 1 3 C NMR
(CH3 CO), 16.30 (C-6e) ppm. HRMS (ESI): calcd. for (100.6 MHz, CDCl3): δ = 214.85 (C=S), 139.33, 139.22, 138.84,
C83H83NO16SNa [M + Na]+ 1404.5325; found 1404.5375.
Phenyl (3,4,6-Tri-O-benzyl-β- -galactopyranosyl)-(1Ǟ4)-[2,3,4-tri-
O-benzyl-α- -fucopyranosyl-(1Ǟ3)]-6-O-benzyl-2-deoxy-2-phthal-
imido-1-thio-β- -glucopyranoside (8): To a solution of 7 (0.45 g,
0.325 mmol) in dry CH2Cl2 (12 mL) was added freshly prepared
Mg(OMe)2 solution (12 mL, 1.4 mol/L). The reaction mixture was
stirred for 72 h at room temperature under argon. The mixture was
neutralized to pH 7 with acetic acid, filtered, and concentrated. The
residue was dissolved in CH2Cl2 and washed with water, dried with
MgSO4, and concentrated. The residue was purified by flash col-
umn chromatography (Cy/EtOAc = 5:1). Compound 8 was ob-
tained (0.4 g, 93%) as a white amorphous solid. Rf = 0.47 (Cy/
EtOAc = 2:1). [α]2D0 = –9 (c = 1.0; CHCl3). 1H NMR (400 MHz,
138.38, 138.31, 138.06, 137.96, 132.75 (Ar-C), 132.38, 128.87–
127.09, 123.82 (Ar-CH), 100.05 (C-1d), 96.98 (C-1e), 84.45 (C-1c),
81.13 (C-3d), 80.47 (C-2d), 79.63 (C-5c), 79.34 (C-3e), 78.77 (C-
4e), 74.69 (C-4c), 74.38 (C-2e), 73.62 (C-4d), 72.82 (C-5d), 72.37
(C-3c), 75.45, 75.08, 73.39, 73.38, 72.72, 72.32, 72.06 (7ϫ PhCH2),
68.25 (C-6c), 67.66 (C-6d), 66.72 (C-5e), 55.86 (C-2c), 19.86 (CH3),
16.84 (C-6e) ppm. HRMS (ESI): calcd. for C83H83NO15S3Na
[M + Na]+ 1452.4817; found 1452.4802.
D
L
D
Phenyl (3,4,6-Tri-O-benzyl-2-deoxy-β-
(1Ǟ4)-[2,3,4-tri-O-benzyl-α- -fucopyranosyl-(1Ǟ3)]-6-O-benzyl-
2-deoxy-2-phthalimido-1-thio-β- -glucopyranoside (10): To a solu-
D-lyxo-hexopyranosyl)-
L
D
tion of 9 (138 mg, 0.096 mmol) in dry toluene (10 mL) containing
AIBN (3.9 mg, 0.024 mmol) was added tributyltin hydride
CDCl3): δ = 7.76–6.97 (m, 44 H, Ar-H), 5.52 (d, J = 10.6 Hz, 1 H, (0.26 mL, 0.96 mmol). The mixture was stirred at 80 °C for 1 h,
1c-H), 4.90 (d, J = 10.8 Hz, 1 H, PhCHH), 4.82–4.80 (m, 2 H, 2c-
H, PhCHH), 4.79 (d, J = 4.2 Hz, 1 H, 1e-H), 4.73, 4.72 (2ϫ d, J
then concentrated and purified by flash column chromatography
(toluene/ethyl acetate = 30:1) to give 10 (111 mg, 87%) as a white
= 11.8 Hz, 2 H, PhCH2), 4.58–4.49 (m, 8 H, 1d-H, 2c-H, 5e-H, foam. Rf = 0.44 (toluene/ethyl acetate = 10:1). [α]2D0 = –12 (c = 1.0;
PhCH2), 4.42 (d, J = 12.4 Hz, 1 H, PhCHH), 4.41 (d, J = 11.8 Hz,
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.68–6.90 (m, 44 H, Ar-
1 H, PhCHH), 4.36 (d, J = 11.8 Hz, 1 H, PhCHH), 4.22–4.20 (m, H), 5.44 (d, J = 10.5 Hz, 1 H, 1c-H), 4.82 (d, J = 10.8 Hz, 1 H,
1 H, 4c-H), 4.16 (d, J = 12.4 Hz, 1 H, PhCHH), 4.09–4.05 (m, 1 PhCHH), 4.70–4.60 (m, 3 H, 1e-H, 3c-H, PhCHH), 4.57–4.51 (m,
H, 6c-H), 4.00 (d, J = 11.2 Hz, 1 H, PhCHH), 3.97–3.97 (m, 1 H,
4d-H), 3.93–3.88 (m, 1 H, 6cЈ-H), 3.86–3.85 (m, 1 H, 2d-H), 3.83–
4 H, 1d-H, 5e-H, PhCH2), 4.48–4.43 (m, 3 H, 2c-H, PhCH2), 4.42–
4.29 (m, 6 H, PhCH2), 4.13 (d, J = 12.4 Hz, 1 H, PhCHH), 4.05
3.82 (m, 1 H, 3e-H), 3.78–3.76 (m, 1 H, 5c-H), 3.71–3.62 (m, 3 H, (t, J = 9.5 Hz, 1 H, 4c-H), 3.87 (d, J = 11.2 Hz, 1 H, PhCHH),
2e-H, 2 ϫ 6d-H), 3.43–3.39 (m, 1 H, 5d-H), 3.34 (dd, J = 9.7, 3.82–3.81 (m, 1 H, 4d-H), 3.79–3.74 (m, 2 H, 3e-H, 6-H), 3.71–
2.8 Hz, 1 H, 3d-H), 3.26–3.25 (m, 1 H, 4e-H), 1.03 (d, J = 6.4 Hz, 3 3.66 (m, 2 H, 2ϫ 6-H), 3.62–3.58 (m, 3 H, 2e-H, 5c-H, 6-H), 3.35
H, 6e-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 139.17, 139.04, (ddd, J = 9.6, 2.4 Hz, 1 H, 3d-H), 3.28–3.24 (m, 1 H, 5d-H), 3.20–
138.91, 138.42, 138.24, 137.95, 132.53 (Ar-C), 134.15, 132.45, 3.19 (m, 1 H, 4e-H), 1.92–1.80 (m, 2 H, 2d-H), 0.95 (d, J = 6.4 Hz,
128.87–127.16, 123.66 (Ar-CH), 101.69 (C-1d), 97.83 (C-1e), 84.09
(C-1c), 82.42 (C-3d), 79.65 (C-5c), 79.41 (C-3e), 78.35 (C-4e), 75.00 139.27, 139.12, 138.38, 138.34, 138.27, 138.11, 132.59 (Ar-C),
3 H, 6e-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 139.28,
(C-4c), 74.34 (C-2e), 73.33 (C-4d), 72.97 (C-5d), 75.34, 74.90,
73.42, 73.24, 72.81, 72.64, 72.17 (7ϫ PhCH2), 71.68 (C-2d), 68.66
(C-6c), 67.93 (C-6d), 66.76 (C-5e), 55.66 (C-2c), 16.50 (C-6e) ppm.
HRMS (ESI): calcd. for C81H81NO15SNa [M + Na]+ 1362.5219;
found 1362.5253.
134.18, 132.43, 128.88–127.13, 123.71 (Ar-CH), 99.46 (C-1d), 97.62
(C-1e), 84.19 (C-1c), 79.76 (C-2e), 79.48 (C-3e), 78.46 (C-4e), 77.67
(C-3d), 74.58 (C-4c), 74.38 (C-5c), 73.85 (C-3c), 73.50 (C-5d), 72.30
(C-4d), 75.17, 74.91, 73.48, 73.46, 72.80, 72.09, 70.55 (7ϫ PhCH2),
68.93 (C-6c), 68.48 (C-6d), 66.65 (C-5e), 55.71 (C-2c), 32.90 (C-
2d), 16.55 (C-6e) ppm. HRMS (ESI): calcd. for C81H81NO14SNa
[M + Na]+ 1346.5270; found 1346.5314.
Phenyl [3,4,6-Tri-O-benzyl-2-O-(methylthio)thiocarbonyl-β-
topyranosyl]-(1Ǟ4)-[2,3,4-tri-O-benzyl-α- -fucopyranosyl-(1Ǟ3)]-6-
O-benzyl-2-deoxy-2-phthalimido-1-thio-β- -glucopyranoside (9): To
D-galac-
L
D
2-(Trimethylsilyl)ethyl (3,4,6-Tri-O-benzyl-2-deoxy-β-
pyranosyl)-(1Ǟ4)-[2,3,4-tri-O-benzyl-α- -fucopyranosyl-(1Ǟ3)]-6-
O-benzyl-2-deoxy-2-phthalimido-β- -glucopyranosyl-(1Ǟ3)-(2,6-
di-O-benzyl-β- -galactopyranosyl)-(1Ǟ4)-2,3,6-tri-O-benzyl-β-
D-lyxo-hexo-
an ice-cooled solution of 8 (118 mg, 0.088 mmol) and imidazole
(1.2 mg, 0.018 mmol) in dry THF (5 mL) was added sodium hy-
dride (6.9 mg, 0.176 mmol). The mixture was stirred for 1 h at room
temperature under argon, and carbon disulfide (52 μL, 0.88 mmol)
was then added. Stirring was continued for 20 min, and methyl io-
dide (52 μL, 0.88 mmol) was added, and the mixture was stirred
for 2 h. MeOH was added at 0 °C to destroy the excess of sodium
hydride. The mixture was concentrated, the residue was taken up
in ether, and the extract was washed successively with water, 1 m
hydrochloric acid, and water, dried with MgSO4, and concentrated.
After purification by flash column chromatography (Cy/EtOAc =
5:1), compound 9 was obtained (117 mg, 93%) as a white amorph-
ous solid. Rf = 0.47 (Cy/EtOAc = 2.5:1). [α]2D0 = –12 (c = 1.0;
CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.70–6.89 (m, 44 H, Ar-
H), 6.12 (dd, J = 8.2, 9.6 Hz, 1 H, 2d-H), 5.38 (d, J = 10.5 Hz, 1
L
D
D
D-
glucopyranoside (12): A mixture of 10 (220 mg, 0.166 mmol), 11
(178 mg, 0.199 mmol), and powdered molecular sieves (4 Å,
400 mg) was stirred in dry CH2Cl2 (12 mL) for 30 min at room
temperature under nitrogen, then cooled to –20 °C. NIS (83.5 mg,
0.37 mmol), then TfOH (5 μL, 0.056 mmol) were added and the
temperature was raised slowly to room temperature. The mixture
was neutralized with Et3N after stirring at room temperature for
an additional 1 h, filtered through Celite, and washed with aqueous
sodium thiosulfate, brine and then dried with MgSO4 and concen-
trated. After purification by flash column chromatography (Cy/
EtOAc = 6:1), 12 was obtained (300 mg, 86%) as a white foam. Rf
1
= 0.42 (Cy/EtOAc = 2.5:1). [α]2D0 = –6 (c = 1.0; CHCl3). H NMR
H, 1c-H), 4.82 (d, J = 10.6 Hz, 1 H, PhCHH), 4.71 (d, J = 12.0 Hz, (400 MHz, CDCl3): δ = 7.38–6.77 (m, 64 H, Ar-H), 5.31 (d, J =
1 H, PhCHH), 4.62 (d, J = 3.0 Hz, 1 H, 1e-H), 4.60–4.57 (m, 2 H,
1d-H, 3c-H), 4.56–4.48 (m, 4 H, 5e-H, PhCH2), 4.44 (d, J =
10.5 Hz, 1 H, 2c-H), 4.40–4.20 (m, 7 H, PhCH2), 4.13 (d, J =
12.2 Hz, 1 H, PhCHH), 4.05 (t, J = 9.5 Hz, 1 H, 4c-H), 3.94–3.90
8.4 Hz, 1 H, 1c-H), 4.91 (d, J = 10.6 Hz, 1 H, PhCHH), 4.85 (dd,
J = 11.3 Hz, 2 H, PhCH2), 4.69 (d, J = 3.0 Hz, 1 H, 1e-H), 4.67–
4.52 (m, 8 H, 1d-H, 5e-H, PhCH2), 4.49 (d, J = 10.9 Hz, 1 H,
PhCHH), 4.46–4.41 (m, 5 H, 2c-H, PhCH2), 4.39–4.36 (m, 3 H,
Eur. J. Org. Chem. 2011, 7133–7139
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7137

Y. Zhang et al.
FULL PAPER
PhCH2), 4.34–4.24 (m, 5 H, 1a-H, PhCH2), 4.22–4.20 (m, 2 H, 1b- white amorphous solid. Rf = 0.54 (Cy/EtOAc = 1:1). [α]2D0 = –25 (c
1
H, PhCHH), 4.19 (d, J = 11.5 Hz, 1 H, PhCHH), 4.11, 4.08 (2ϫ
d, J = 11.4 Hz, 4 H, PhCH2), 3.95 (d, J = 11.2 Hz, 1 H, PhCHH),
3.92–3.84 (m, 2 H, 1 H, OCHH), 3.81–3.76 (m, 2 H), 3.72–3.60 (m,
7 H, 6-H, 2e-H), 3.52–3.42 (m, 4 H, 1 H, OCHH, 6-H), 3.40–3.26
(m, 7 H, 3d-H, 6-H), 2.99–2.96 (m, 1 H), 2.77 (br. s, 1 H, OH),
1.98–1.96 (m, 2 H, 2d-H), 1.00 (d, J = 6.4 Hz, 3 H, 6e-H), 0.97–
= 1.0; CHCl3). H NMR (400 MHz, CDCl3): δ = 7.44–7.16 (m, 60
H, Ar-H), 5.59 (d, J = 7.6 Hz, 1 H, NH), 5.30 (d, J = 6.7 Hz, 1 H,
1c-H), 5.01 (d, J = 10.6 Hz, 1 H, PhCHH), 4.92–4.89 (m, 3 H, 1e-
H, PhCH2), 4.83 (d, J = 12.1 Hz, 1 H, PhCHH), 4.75–4.60 (m, 10
H, PhCH2), 4.57–4.46 (m, 5 H, 1d-H, PhCH2), 4.44–4.29 (m, 8 H,
1a-H, 1b-H, 5e-H, PhCH2), 4.19–4.16 (m, 2 H, 3c-H, PhCHH),
0.94 (m, 2 H, OCH2CH2Si), 0.02 (s, 9 H, SiMe3) ppm. 13C NMR 4.03–3.82 (m, 6 H, 2e-H, 3e-H, 4c-H, OCHCH2Si), 3.77–3.59 (m,
(100.6 MHz, CDCl3): δ = 139.19, 139.18, 139.06, 138.92, 138.68, 8 H, 6-H), 3.57–3.41 (m, 9 H, 2a-H, 2c-H, 3d-H, 6-H, OCHCH2Si),
138.43, 138.33, 138.30, 138.07, 137.94, 131.34 (Ar-C), 133.78– 3.39–3.30 (m, 4 H, 2b-H), 1.98–1.96 (m, 2 H, 2d-H), 1.36 (s, 3 H,
123.30 (49 Ar-CH), 103.10 (C-1b), 102.06 (C-1a), 99.44 (C-1d),
99.02 (C-1c), 97.61 (C-1e), 83.47, 82.96, 81.98, 79.37, 78.42, 78.15,
77.61, 76.08, 75.15, 74.78, 74.75, 74.58, 73.61, 72.85, 72.79, 72.22,
Ac), 1.05–1.03 (m, 2 H, OCH2CH2Si), 1.01 (d, J5,6 = 6.4 Hz, 3 H,
6e-H), 0.03 (s, 9 H, SiMe3) ppm. 13C NMR (100.6 MHz, CDCl3): δ
= 170.34 (MeC=O), 139.30, 139.21, 139.14, 139.06, 139.00, 138.82,
67.62, 66.65 (ring CH), 75.43, 75.09, 74.95, 74.87, 74.17, 73.58, 138.77, 138.56, 138.36, 138.09, 138.01 (Ar-C), 128.70–127.30 (Ar-
73.42, 73.04, 72.65, 72.12, 70.54 (PhCH2), 68.93, 68.66, 68.50, CH), 103.22 (C-1b), 102.42 (C-1a), 99.64 (C-1d), 99.56 (C-1c),
67.97, 67.25 (4ϫ C-6, OCH2CH2Si), 56.39 (C-2c), 32.78 (C-2d), 97.86 (C-1e), 83.12, 82.14, 79.88, 79.25, 78.24, 77.48, 77.36, 76.72,
18.50 (OCH2CH2Si), 16.56 (C-6e), –1.34 (SiMe3) ppm. HRMS
(ESI): calcd. for C127H139NO25SiNa [M + Na]+ 2128.9298; found
2128.9338.
76.10, 75.22, 74.82, 74.01, 73.78, 73.61, 73.00, 72.28, 67.53, 66.62
(ring CH), 75.54, 75.16, 75.06, 75.02, 74.78, 73.66, 73.54, 73.52,
73.44, 73.23, 72.35 (PhCH2), 70.53, 69.46, 68.77, 68.52, 67.41 (4ϫ
C-6, OCH2CH2), 57.23 (C-2c), 33.04 (C-2d), 23.03 (CH3CO), 18.61
(OCH2CH2Si), 16.62 (C-6e), –1.27 (SiMe3) ppm. HRMS (ESI):
calcd. for C121H139NO24SiNa [M + Na]+ 2040.9349; found
2040.9407.
2-(Trimethylsilyl)ethyl (3,4,6-Tri-O-benzyl-2-deoxy-β-
pyranosyl)-(1Ǟ4)-2,3,4-tri-O-benzyl-α- -fucopyranosyl-(1Ǟ3)-6-
O-benzyl-2-deoxy-2-phthalimido-β- -glucopyranosyl-(1Ǟ3)-(4-O-
acetyl-2,6-di-O-benzyl-β- -galactopyranosyl)-(1Ǟ4)-2,3,6-tri-O-
benzyl-β- -glucopyranoside (12Ј): A solution of 12 (45 mg) and
D-lyxo-hexo-
L
D
D
D
2-(Trimethylsilyl)ethyl (2-Deoxy-β-
-fucopyranosyl-(1Ǟ3)]-2-deoxy-2-acetamido-β-
(1Ǟ3)-(β- -galactopyranosyl)-(1Ǟ4)-β- -glucopyranoside (1): A
D-lyxo-hexopyranosyl)-(1Ǟ4)-[α-
DMAP (20 mg) in pyridine (1 mL) and acetic anhydride (0.5 mL)
was stirred at room temperature for 14 h and then concentrated,
co-evaporated with toluene and dried. Compound 12Ј was obtained
(44 mg, 96 %) as a white foam. Rf = 0.46 (Cy/EtOAc = 2.5:1).
[α]2D0 = –5 (c = 1.0; CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.39–
6.82 (m, 64 H, Ar-H), 5.45 (d, J = 3.5 Hz, 1 H, 4b-H), 5.23 (d, J
= 8.3 Hz, 1 H, 1c-H), 4.89–4.81 (m, 4 H, PhCH2), 4.75 (m, 9 H,
1d-H, 1e-H, 5e-H, PhCH2), 4.56 (m, 13 H, 2c-H, PhCH2), 4.27 (m,
6 H, 1a-H, 1b-H, PhCH2), 4.14–4.10 (m, 2 H), 3.96–3.87 (m, 4 H,
1 H, OCHH), 3.84–3.74 (m, 5 H, 6-H), 3.67–3.59 (m, 4 H, 2e-H,
6-H), 3.54–3.43 (m, 3d-H, 1 H, OCHH, 6-H), 3.39–3.24 (m, 9 H,
6-H), 2.99–2.96 (m, 1 H), 2.07 (s, 3 H, Ac), 1.99–1.97 (m, 2 H, 2d-
H), 1.01 (d, J = 6.3 Hz, 3 H, 6e-H), 0.96–0.89 (m, 2 H,
OCH2CH2Si), 0.01 (s, 9 H, SiMe3) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 170.05 (MeC=O), 139.36, 139.28, 139.22, 138.94,
138.73, 138.46, 138.39, 138.37, 138.16 (Ar-C), 128.70–126.51 (64
Ar-CH), 103.21 (C-1b), 102.16 (C-2a), 99.42 (C-1d), 99.32 (C-1c),
97.26 (C-1e), 82.80, 81.90, 79.42, 78.88, 78.80, 78.63, 77.80, 77.36,
75.90, 77.99, 75.56, 74.80, 74.63, 74.40, 73.38, 72.80, 72.37, 72.09,
70.29, 66.54 (CH), 75.26, 75.22, 75.04, 74.92, 74.24, 73.62, 73.60,
73.45, 73.18, 72.56, 72.15, 70.60 (PhCH2), 68.89, 68.49, 68.40,
67.80, 67.36 (4ϫ C-6, OCH2), 56.94 (C-2c), 32.99 (C-2d), 20.94
(CH3, Ac), 18.57 (OCH2CH2Si), 16.56 (C-6e), –1.28 (SiMe3) ppm.
HRMS (ESI): calcd. for C129H141NO26SiNa [M + Na]+ 2170.9403;
found 2170.9469.
L
D
-glucopyranosyl-
D
D
solution of 13 (80 mg) in MeOH (10 mL) was treated with Pd/C
(10%, 35 mg) under H2 for 20 h at 30 °C, then filtered and the
solvents evaporated. The residue was purified on a Sephadex col-
umn (G25) using water as eluant. Compound 1 was obtained as a
white amorphous solid (35 mg, 95%). Rf = 0.53 (2-propanol/ethyl
acetate/water = 3:3:2). [α]2D0 = –28 (c = 1.0; MeOH). 1H NMR
(400 MHz, D2O): δ = 5.16 (d, J = 4.0 Hz, 1 H, 1e-H), 4.86–4.72
(m, 3 H, 1c-H, 1d-H, 5e-H), 4.52 (d, J = 8.0 Hz, 1 H, 1-H), 4.46
(d, J = 7.8 Hz, 1 H, 1-H), 4.18 (d, J = 3.1 Hz, 1 H), 4.10–3.88 (m,
8 H, 2c-H, 3d-H, 6-H, OCHCH2Si), 3.86–3.71 (m, 13 H, 2e-H, 6-
H, OCHCH2Si), 3.68–3.50 (m, 6 H, 2-H), 3.34–3.29 (m, 1 H, 2-H),
2.05 (s, 3 H, Ac), 2.03–2.02 (m, 1 H, 2d-H), 1.72–1.64 (m, 1 H,
2dЈ-H), 1.22 (d, J = 6.6 Hz, 3 H, 6e-H), 1.05 (2ϫ dt, J = 12.9, J =
5.6 Hz, 2 H, CH2Si), 0.06 (s, 9 H, SiMe3) ppm. 13C NMR
(100.6 MHz, D2O): δ = 174.70 (C=O, NHAc), 102.84, 102.50,
101.76, 101.28 (C-1a, C-1b, C-1c, C-1d), 98.43 (C-1e), 82.11, 78.30,
75.26, 74.95, 74.85, 74.81, 74.74, 74.52, 73.46, 71.94, 69.96, 69.18,
68.29, 67.74, 67.69, 66.73, 66.46 (ring, CH), 72.82 (C-2), 68.43
(OCH2CH2Si), 61.84, 60.94, 60.05, 59.87 (C-6a, C-6b, C-6c, C-6d),
55.96 (C-2c), 33.23 (C-2d), 22.26 (CH3CO), 17.56 (CH2Si), 15.36
(C-6e), –2.53 (SiMe3) ppm. HRMS (ESI): calcd. for C37H67NO24-
SiNa [M + Na]+ 960.3714; found 960.3679.
Supporting Information (see footnote on the first page of this arti-
cle): 1H NMR, 13C NMR, and HR mass spectra of all compounds.
2-(Trimethylsilyl)ethyl (3,4,6-Tri-O-benzyl-2-deoxy-β-
pyranosyl)-(1Ǟ4)-[2,3,4-tri-O-benzyl-α- -fucopyranosyl-(1Ǟ3)]-6-
O-benzyl-2-deoxy-2-acetamido-β- -glucopyranosyl-(1Ǟ3)-(2,6-di-
O-benzyl-β- -galactopyranosyl)-(1Ǟ4)-2,3,6-tri-O-benzyl-β-D-
D-lyxo-hexo-
L
D
Acknowledgments
D
glucopyranoside (13): To a solution of 12 (124 mg, 0.059 mmol) in
EtOH (16 mL), were added hydrazine monohydrate (1 mL) and
H2O (1 mL). The mixture was heated to reflux for 2 h. After con-
centration, the residue was co-evaporated with toluene and dried
with P2O5, then dissolved in MeOH/CH2Cl2 (1:1, 5 mL), to which
acetic anhydride (0.5 mL) was introduced. The mixture was stirred
at room temperature for 2 h. After concentration, the residue was
purified by flash column chromatography (Cy/EtOAc = 3:1), and
then by a Sephadex column (LH-20) using MeOH/CH2Cl2 (1:1) as
eluant. Compound 13 was obtained (100 mg, 84%, two steps) as a
We thank the China Scholarship Council (CSC) for a PhD fellow-
ship to Yanyan Zhang. Financial support from the Centre National
de la Recherche Scientifique (CNRS) and the Université Pierre et
Marie Curie (UPMC) are gratefully acknowledged.
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Received: July 20, 2011
Published Online: October 18, 2011
Eur. J. Org. Chem. 2011, 7133–7139
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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