New thioglycoside derivatives for use in odourless synthesis of MUXF3 N-glycan fragments related to food allergens

Article abstract of DOI:10.1016/j.tet.2007.11.002

Thioglycosides are valuable tools for complex oligosaccharides' constructions. They present precious advantages due to their stability and crystalline nature. However, their major drawbacks are the repulsive smell of thiols utilised as precursors and, oft

Full text of DOI:10.1016/j.tet.2007.11.002

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1523e1535
www.elsevier.com/locate/tet
New thioglycoside derivatives for use in odourless synthesis
of MUXF3 N-glycan fragments related to food allergens
*
Mayeul Collot, Julie Savreux, Jean-Maurice Mallet
De´partement de Chimie, UMR CNRS 8642, Ecole Normale Supe´rieure, 24 rue Lhomond, 75005 Paris, France
Received 1 August 2007; received in revised form 29 October 2007; accepted 1 November 2007
Available online 5 November 2007
Abstract
Thioglycosides are valuable tools for complex oligosaccharides’ constructions. They present precious advantages due to their stability and
crystalline nature. However, their major drawbacks are the repulsive smell of thiols utilised as precursors and, often, their toxicity such as in case
of the commonly employed thiophenol and thioethanol. The use of commercially available methyl tert-butyl phenyl thiol (MbpSH) avoids these
problems and is compatible with gram scale synthesis of thioglycoside donors. In this paper, we describe that Mbp thioglycosides are useful and
convenient precursors for odourless oligosaccharide synthesis and we further demonstrate, as a proof of their versatility, their use in the con-
struction of most of the glycosidic linkages found in N-glycans.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Thioglycosides; Odourless thiol; Allergy; MUXF3; N-Glycan; CCD; Cross-reactive carbohydrate determinants; Oligosaccharides
1. Introduction
odour of thiol precursors (thioethanol, thiophenol and thiocre-
sol) even far below the toxic concentration, a property for
which they find an application as additives for gas odorisation.
Hence, despite their great utility in oligosaccharide synthesis,
thioglycosides remain an undesirable area of sugar chemistry
for many research groups.
Along with trichloroacetimidates, thioglycosides are reli-
able glycosyl donors for the multi-step construction of com-
plex oligosaccharides.1 Although introduced about two
decades ago, they are yet not surpassed and are widely used.
They are reactive enough to be used at low temperature,
thus allowing good alpha regioselectivity in the absence of
a participating group at position 2, and, moreover, their activa-
tion does not require the presence of a heavy metal. Thiogly-
cosides are usually less reactive than imidates but are much
more stable at room temperature and are often crystalline
and they are, therefore, more convenient for routine oligosac-
charide synthesis,2 both in solution and solid phase. Another
precious advantage is that the thioglycoside group can be
used for a protection of the anomeric position, while imidate
chemistry requires extra protecting groups, such as acetate
or trimethylsilylethyl groups, and, thus, more synthetic steps.
The major drawback of thioglycoside chemistry is the foul
Some efforts have been made in this respect to find odour-
less surrogates for those thiols in glycosylation. One of these is
the commercially available methyl thiosalicylate developed by
Kobayashi.3 However, in this case, the thioglycoside reactivity
is reduced by the electron-withdrawing groups and, further-
more, ester functions can interfere with multi-step strategies.
Node’s group4 prepared phenylmethanethiol derivatives while
Huang et al.5 published non-commercial fluorous thiols for
thioglycoside preparation. These thiols are effective, but of
high molecular weight and require a multi-step preparation.
Some other thiols were proposed as odourless deprotecting
reagents,6 such as dimethylamino ethanethiol,7 and lastly
2-methyl-5-tert-butylthiophenol (MbpSH) (Fig. 1). Kumar
et al.8 used this commercially available thiol as an odourless
deprotecting agent for nucleotide chemistry. The complete
loss of odour is probably due to the presence of a bulky group
next to the thiol group. It is non-volatile (bp 260 ꢀC,
* Corresponding author. Fax: þ33 01 44 32 33 97.
E-mail address: jean-maurice.mallet@ens.fr (J.-M. Mallet).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.002

1524
M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
and a-L-fucose on the inner chitobioside unit. These two gly-
HS
cosydic linkages, also present in the invertebrate kingdom,
are known to be immunogenic.15
2. Result and discussion
Figure 1. 2-Methyl-5-tert-butylthiophenol.
We thus envisaged a synthetic route towards biotinylated
fragments of MUXF3 oligosaccharides via a novel thiol
methodology using MbpSH for the preparation of efficient
glycosyl donors required for the synthesis of the two branched
trisaccharides 1 (a-Man1/6)[b-Xyl(1/2)]b-Man- and 2
(b-GlcNAc1/4)[a-Fuc(1/3)b-GlcNAc (Fig. 3). These com-
pounds would bear a connector suitable for solid phase
diagnosis, whereas, the acid function would be used for bead
or plates antigen immobilisation.16 These syntheses were per-
formed on a large scale, on important sugars (Man, Glc, Fuc,
Xyl, GlcNAc) and were based on our previous work and
knowledge on mannosides16 and on glucosamine containing
oligosaccharides.17
mp ꢁ10 ꢀC) and its toxicity (irritant Xi) is largely reduced
compared to that of thiophenol (highly toxic Tþ). This thiol
is similar to 2,5-dimethyl phenyl thiol used by Glidersleeve9
and will, probably, avoid in the same way the glycoside trans-
fer, a major side reaction in deceiving glycosylation reactions.
In the launch of our program on food allergies, which rep-
resent a major problem in our society, we were interested in the
synthesis of MUXF3 oligosaccharidic fragments.10 It is well
known that a large part of the population (4% to up to 30%)
presents immune reaction to food allergens. This reaction is
promoted by the recognition of food glycoproteins by the pa-
tient’s IgE. In such cases, each patient is a particular case and
presents his own recognition pattern of the plant glycoprotein
repertoire, a fact which renders the study of allergens rather
complicated. In a large number of cases, IgE are directed
against the sugar part of the plant or invertebrate protein. In
the case of tomato and celery,11 for example, up to 30% of
the allergic patient recognise the N-glycan part (Fig. 2). These
N-glycans are known as ‘cross-reactive carbohydrate deter-
minants’ CCD.12 The role of CCD antigens is rather confused
in the literature. They are present on glycoprotein but are not
harmful,13 probably due to a generally low density of pre-
sented epitopes. The evaluation of their participation to the
global allergic response is particularly critical with the recent
use of recombinant allergenic protein for diagnosis.14
The monosaccharidic building thioglycosidesdwith or
without a participating group in position 2dused in this
work are presented in Figure 4.
The syntheses of these building blocks are presented in the
following scheme. The glucosyl donor 3 was readily prepared
from the corresponding orthoester18 and MbpSH in presence
of catalytic amount of mercuric bromide.2d In this reaction,
a thiophilic Lewis acid was found to be the optimum choice.
Less toxic but more oxophilic Lewis acids, such as TMSOTf,
BF3$Et2O or zinc halides, gave less satisfactory results, fa-
vouring the formation of the competing ethyl glycoside. Alter-
natively, a convenient two-step strategy in the absence of
mercury salts has also been employed through the 1,2-di-O-
acetyl analogue 13 (Scheme 1). This method led to a mixture
of anomers, which could be used as such for the glycosylation
reaction. Due to the fact that a benzoyl group is a better par-
ticipating group in glycosylations, the acetate group in product
12 was further replaced with a benzoate in high yielding
transformations.
These N-glycans are close to the human glycans present on
glycoproteins but contain two non-human glycosylation pat-
terns: a b-D-xylose in the position 2 of the branched mannose
Manα1
6
Manβ1-4GlcNAcβ1-4GlcNAc
MUX
2
The peracyl or perbenzyl thioglycosides were prepared as
described in Scheme 2. The key step was the replacement19
Xylβ1
Manα1
6
BzO
MUXF3
Manβ1-4GlcNAcβ1-4GlcNAc
BzO
Manα1
2
3
BzO
OBz
O
O
BzO
6
BzO
BzO
Manβ-
Xylβ1
Fucα1
O
2
O
O
O
BzO
Manα1
Manα1
Manα1
Manα1
O
Xylβ1
OMe
O
BzO
6
Manβ1-4GlcNAcβ1-4GlcNAc MMF3
1
3
3
Fucα1
Ph
BnO
O
O
O
O
O
O
GlcNAcβ1-4GlcNAc
OEt
O
AcO
3
NPhth
NPhth
6
MMXF3
Fucα1
O
Manβ1-4GlcNAcβ1-4GlcNAc
OBn
3
2
3
BnO
OBn
Xylβ1
Fucα1
2
Figure 2. Typical oligosaccharides from plant N-glycans.
Figure 3. Compounds 1 and 2.

M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1525
OBn
O
of the anomeric acyloxy group by the MbpS group in the
presence of BF3$OEt2 in D-xylose perbenzoate,20 D-mannose
perbenzoate,21 1,3,4,6-tetra-O acetyl-2-deoxy-2-phthalimido
glucose 1522 and L-fucose peracetate 16.23
O
BzO
BzO
BnO
BnO
S
S
OBz
OBz
4
Compound 6 was deacetylated and was subsequently re-
acted with benzylaldehyde dimethyl acetal to yield 18. Three
different protecting groups were then used (Ac, Bn, TBS) for
the position 3 to give compounds 8, 9 and 10, respectively
(Scheme 3).
3
BzO
BzO
BzO
OBz
O
OAc
O
S
AcO
AcO
S
NPhth
5
18 R=H
O
a,b
c
Ph
O
6
SMbp
O
d
6
RO
9 R=Bn
10 R=TBS
8 R=Ac
e
NPhth
O
Ph
O
O
S
S
O
RO
OBn
Scheme 3. Reagents and conditions: (a) MeONa, MeOH, 2 h, rt; (b) benzalde-
hyde dimethylacetal, CSA, CH3CN, 1 h, 90% (two steps); (c) NaH, BnBr,
THF, 3 h, reflux, 63%;10b (d) TBSOTf, pyridine, 1 h, rt, 94%; (e) Ac2O, pyri-
dine, 15 h, rt, 93%.
NPhth
OBn
OBn
8 R=Ac
9 R=Bn
10 R=TBS
7
Having all these blocks in hand, we started building up the
trisaccharides 1 and 2. The synthesis of the trisaccharide 1 is
depicted in Scheme 4. The b-mannosidic linkage is usually
considered to be difficult to construct starting with a mannosyl
derivative. In our case, it was quite straightforward to be ob-
tained from a b-glucosyl analogue through an oxidationere-
duction sequence, since, upon this process the hydride comes
from the less hindered face of the keto group (such as in com-
pound 21). This strategy is practically convenient when the
position 2 is to be glycosylated in the next step as already
described for the b(1/2) oligomannoside synthesis.24 Subse-
quently, a b-xylopyranosyl unit was introduced on position 2,
and the benzyl groups were removed to give compound 24.
To differentiate the position 6 of the b-manno unit, we de-
cided to selectively silylate this position and to benzoylate in
a one-pot method the 3- and 4-positions of this fragment. Us-
ing TBAF in THF for the desilylation step of 25, a complete
migration of the 4-benzoate to the 6-position to give com-
pound 27 was observed (Fig. 5). This migration is rather fre-
quent with acetate groups but less frequent with benzoate.
Nevertheless, this unwanted reaction was avoided using an
acidic fluorine source (aq HF) to afford compound 26, which
was then mannosylated with compound 5 to give trisaccharide
1 in a high yield.
Figure 4. Mbp thioglycosides used in this work.
OBn
O
OBn
12 R=Ac
14 R=H
3 R=Bz
BnO
BnO
O
a
b
c
BnO
BnO
S
O
O
OR
OEt
11
d
OBn
e
O
BnO
BnO
OAc
OAc
13
Scheme 1. Reagents and conditions: (a) 2-methyl-5-tert-butylthiophenol,
HgBr2, toluene, 80 ꢀC, 3 h, 64%; (b) MeONa/MeOH, 40 ꢀC, 12 h, 82%; (c)
BzCl, Et3N, DMAP, CH2Cl2, 25 ꢀC, 12 h, 95%; (d) AcOH, rt, 30 min; (e)
2-methyl-5-tert-butylthiophenol, BF3$Et2O, toluene, rt, 2 h, 65% (two steps).
a, b
4
D-Xylose
α/β : 8/92
c, d
D-Mannose
5
α/β : 90/10
Alternatively, the acetylated glycosyl donor 12 was coupled
with ethyl 6-hydroxy hexanoate to give 28 (Fig. 5). As ex-
pected, the yield was moderate (69%) compared to the benz-
oylated donor 3 (97%), validating our choice for the benzoyl
group at position 2.
The synthesis of 2, shown in Scheme 5, illustrates the use
of glucosamine 6 and 8 and of the benzylated fucose donors 7.
The ethyl 6-hydroxy hexanoate was glycosylated (NBS,
TfOH) with 6 in a very high yield to give 29. The acetate
groups were removed and an acetal was selected to protect
the positions 4 and 6 to give 30. L-Fucose was subsequently
introduced using the glycosyl donor 7 to give 31 (83%) as
an a/b mixture, non-separable at this stage (a/b 85:15). The
OAc
O
OAc
e
AcO
AcO
6
NPhth
15
OAc
SMbp
O
g, h
OAc
O
f
7
OAc
OAc
OAc
AcO
AcO
16
17
Scheme 2. Reagents and conditions: (a) BzCl, pyridine, 85%; (b) MbpSH,
BF3$OEt2, CH2Cl2, 85%; (c) BzCl, pyridine, 95%; (d) MbpSH, BF3$OEt2,
CH2Cl2, 88%; (e) MbpSH, BF3$OEt2, CH2Cl2, 98%; (f) MbpSH, BF3$OEt2,
CH2Cl2, 97% (a/b 7:1); (g) MeONa, MeOH, 45 min, rt; then NaH, BnBr,
DMF, 2 h, rt, 84% (two steps, pure b anomer).

1526
M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
BnO
O
O
O
BnO
BnO
O
b
a
HO
OEt
OEt
OBz
19
OH
O
BnO
BnO
BnO
BnO
BnO
BnO
BnO
O
O
c
BnO
d
OR
OH
OR
OR
BnO
O
20
21
22
BzO
BzO
BzO
BzO
O
O
g
BzO
BnO
BnO
BnO
f
BzO
O
O
e
HO
O
O
HO
OR
OR
HO
23
24
BzO
BzO
BzO
BzO
O
O
i
h
BzO
1
O
BzO
HO
BzO
BzO
O
TBDMSO
O
BzO
OR
O
BzO
OR
25
26
ꢀ
˚
Scheme 4. Reagents and conditions: (a) 3, NIS, cat TfOH, CH2Cl2, 4 A MS, rt, 97%; (b) MeONa, MeOH, THF, 2 h, 60 C, 89%; (c) (COCl)2, DMSO, Et3N,
ꢀ
˚
45 min, ꢁ78 C; (d) NaBH4, MeOH, CH2Cl2, 12 h, rt, 74% (two steps); (e) 4, NIS, cat. TfOH, CH2Cl2, 4 A MS, rt, 84%; (f) H2 (1.2 bar), 10% Pd/C, AcOEt,
MeOH, 48 h, rt, 92%; (g) TBDMSCl, DMAP, pyridine, 2 h, rt then BzCl, pyridine, 2 h, rt, 70% (two steps, one pot); (g) aq HF, CH3CN, 12 h, rt, 94%; (i) 5,
˚
NIS, cat. TfOH, CH2Cl2, 4 A MS, rt, 98%. [R¼(CH2)5eCO2Me].
BzO
BzO
acetate 8 activated with NIS was found the optimum system
(66% yield, 8 g scale). In those glycosylations, elimination re-
action was favoured, instead, and the glycal 3326 (Fig. 6) was
isolated as a major side product.
O
BzO
BzO
HO
BzO
O
BnO
BnO
O
O
O
O
OR
OEt
BnO
OAc
3. Conclusion
27
28
Figure 5. Compounds 27 and 28.
We have described herein a very convenient alternative
of usual thioglycosides in glycosylation reactions for the
construction of oligosaccharidic fragments 1 and 2. These car-
bohydrate units are ready to be then coupled to an amine
reductive ring-opening of the benzylidene25 afforded the pure
a-L-fucoside 32.
The compound 32 was then glycosylated with b-glucos-
amine donors 8, 9, 10. Like others,10a we noticed the low re-
activity of acceptors such as compound 32. We tried different
donors with various substituents in position 3 (8, 9, 10) in or-
der to increase the reactivity with electron donating protecting
groups. The yields obtained were rather disappointing and the
O
Ph
O
O
AcO
NPhth
33
Figure 6. Compound 33.
O
AcO
AcO
O
O
a
O
Ph
b
OR
HO
OR
O
OEt
AcO
HO
NPhth
NPhth
29
30
OBn
O
O
Ph
O
O
OR
OR
HO
O
O
O
e
c
d
2
NPhth
NPhth
O
OBn
31
OBn
OBn
OBn
OBn
OBn
32
˚
Scheme 5. Reagents and conditions: (a) 6, NBS, TfOH, 4 A MS, CH2Cl2, 99%; (b) EtONa/EtOH; then benzaldehyde dimethylacetal, CSA, CH3CN, 73% (two
ꢀ
˚
˚
steps); (c) 7, NIS, TfOH, 4 A MS, CH2Cl2, 83% (mixture of a and b fucosides); (d) Et3SiH, TfOH, 4 A MS, CH2Cl2, ꢁ78 C, 79% (pure a fucoside); (e) 8,
˚
NIS, TfOH, 4 A MS, CH2Cl2, 66%. [R¼(CH2)5eCO2Et].

M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1527
derived from biotin (such as biotin hydrazide) and evaluated as
synthetic antigen in allergy diagnosis. The Mbp donors, used
in our synthesis, are stable and often crystalline compounds.
Their handling does not require special equipment nor special
expertise in thiol manipulation. We are currently exploiting
this novel thiol methodology in solution and solid phase
synthesis of oligosaccharides.
1.38e1.30 (m, 2H, H9). 13C NMR (100 MHz, CDCl3) d:
173.9 (CO COOMe), 165.9 (2CO Bz), 165.4 (CO Bz), 165.3
(CO Bz), 165.2 (CO Bz), 165.2 (CO Bz), 165.1 (CO Bz),
165.0 (CO Bz), 164.4 (CO Bz), 133.3e128.0 (54C, C Ar),
0
100.0 (C1 ), 99.9 (C1), 97.2 (C1 ), 75.3 (C2), 73.4 (C3), 73.3
00
00
(C5), 70.2 (C2 ), 69.7 (C3 ), 69.6 (C7), 68.7 (C5 ), 68.5 (C2 ),
00
00
0
0
68.1 (C4 ), 68.0 (C3 ), 67.7 (C6), 67.3 (C4), 66.5 (C4 ), 62.2
0
00
00
0
(C6 ), 59.3 (C5 ), 51.2 (OMe), 33.6 (C11), 29.0 (C8), 25.6
(C9), 24.5 (C10). MS FABþ-HRMS m/z [MþNa]þ calcd for
C87H78O26Na 1561.4679, found 1561.4692.
4. Experimental section
4.1. General procedures
4.1.2. 5-Ethoxycarbonylpentyl 4-O-(3-O-acetyl-4,6-
O-benzylidene-2-deoxy-2-phthalimido-b-D-glucopyranosyl)-
3-O-(2,3,4-tri-O-benzyl-a-L-fucopyranosyl)-6-O-benzyl-
2-deoxy-2-phthalimido-b-D-glucopyranoside (2)
All compounds were homogeneous by TLC analysis and
had spectral properties consistent with their assigned struc-
tures. Melting points were determined in capillary tubes in
a Buchi 510 apparatus. Optical rotations were measured with
¨
To a mixture of 32 (8.860 g, 9.240 mmol), 8 (11.11 g,
˚
18.49 mmol, 2.0 equiv) and 4 A molecular sieves (15 g) in an-
a PerkineElmer Model 241 digital polarimeter at 22ꢂ3 ꢀC.
Compound purity was checked by TLC on Silica gel 60 F254
(E. Merck) with detection by charring with sulfuric acid. Col-
hydrous dichloromethane (90 mL), were added under argon,
NIS (1.951 g, 8.672 mmol, 2.0 equiv) and TfOH (0.082 mL,
0.924 mmol, 0.1 equiv). After 2 min the mixture was filtered,
extracted with dichloromethane and washed with saturated
NaHCO3 and Na2S2O3 solutions. The organic layer was dried
(MgSO4), filtered and the solvent was evaporated. The residue
was purified by column chromatography on silica gel (cyclo-
hexane/EtOAc 7:3) to give a mixture of 2 and 33. This mixture
was purified by column chromatography on silica gel (di-
chloromethane) to give 8.39 g of 2 (66%) as a white amor-
phous solid. Rf: 0.22 (cyclohexane/EtOAc 7:3). [a]2D5 ꢁ36 (c
umn chromatography was performed on Silica gel 60 (E.
1
Merck). H and 13C NMR spectra were recorded with Bruker
¨
AM 250, AM 400 instruments. Chemical ionisation and FAB
mass spectrometry were recorded with Jeol MS700: CI (gas:
ammonia); FAB (matrix: NBA, NaI). NIS was purchased
from Fluka [ref. 58070]. Carboxypentyl chain was numbered
7 (OCH2) to 11 in NMR assignments.
4.1.1. 5-Methoxycarbonylpentyl 2-O-(2,3,4-tri-O-benzoyl-
b-D-xylopyranosyl)-3,4-di-O-benzoyl-6-O-(2,3,4,6-tetra-
O-benzoyl-a-D-mannopyranosyl)-b-D-mannopyranoside (1)
To a mixture of 26 (0.895 g, 0.932 mmol), 5 (0.848 g,
1
1.9, CHCl3). H NMR (400 MHz, CDCl3) d: 8.00e7.22 (m,
00
00
00
00
00
33H, H Ar), 5.86 (dd, 1H, JH3 eH2 ¼JH3 eH4 ¼9.6 Hz, H3 ),
00
00
00
5.65 (d, 1H, JH1 eH2 ¼8.3 Hz, H1 ), 5.35 (s, 1H, H benzyl-
˚
0
0
1.118 mmol, 1.2 equiv) and 4 A molecular sieves (1 g) in an-
idene), 5.11 (d, 1H, JH1eH2¼8.5 Hz, H1), 5.07 (d, 1H, JH1 eH2
¼
0
hydrous dichloromethane (6 mL) under argon, were added
NIS (0.419 g, 1.864 mmol, 2 equiv) and TfOH (0.016 mL,
0.184 mmol, 0.2 equiv). The mixture was allowed to stir for
10 min and was then filtered, extracted with dichloromethane
and washed with saturated NaHCO3 and Na2S2O3 solutions.
The organic layer was dried over MgSO4, filtered and the sol-
vent was evaporated. The residue was purified by column
chromatography on silica gel (cyclohexane/EtOAc 7:3) to
give 1.409 g of 1 (98%) as white solid. Rf: 0.32 (cyclohex-
2.8 Hz, H1 ), 4.92 (d, 1H, Jgem¼11.4 Hz, CHPh), 4.71 (m, 2H,
2CHPh), 4.63 (d, 1H, Jgem¼11.4 Hz, CHPh), 4.58e4.48 (m,
00
0
3H, 2CHPh, 1H), 4.43e4.25 (m, 6H, H2, H2 , 2CHPh, H5 ,
1H), 4.16e4.06 (m, 3H, 1H6, CH2 OEt), 3.87e3.73 (m, 5H,
0
H2 , 1H6, H7, 2H), 3.68e3.56 (m, 3H, 2H6, 1H), 3.44e3.32
(m, 3H, H7, 2H), 1.98 (m, 2H, H11), 1.91 (s, 3H, CH3 OAc),
0
0
1.44e1.37 (m, 4H, H8, H10), 1.30 (d, 3H, JH6 eH5 ¼6.4 Hz,
H6 ), 1.25 (t, 3H, J¼7.2 Hz, CH3 OEt), 1.10 (m, 2H, H9). 13C
0
NMR (100 MHz, CDCl3) d: 173.2 (CO COOEt), 170.0 (CO
OAc), 168.6 (CO Phth), 167.8 (CO Phth), 138.6e123.1 (C
ane/EtOAc 7:3). Mp: 98 ꢀC. [a]D25 ꢁ110 (c 1.0, CHCl3). H
1
0
00
NMR (400 MHz, CDCl3) d: 8.18e7.30 (m, 45H, H Ar), 6.18
00
Ar), 101.3 (C benzylidene), 97.9 (C1), 97.6 (C1 ), 96.1 (C1 ),
79.4, 79.0, 78.2, 75.8, 74.9, 74.8 (CH2Ph), 74.4, 73.9, 72.6
00
00
00
00
(t, 1H, JH4 eH3 ¼JH4 eH5 ¼10.0 Hz, H4 ), 5.90 (dd, 1H,
00
00
00
00
00
00
(CH2Ph), 72.5 (2CH2Ph), 69.7 (C3 ), 68.9 (C7), 68.4 (1C6),
00
68.3 (1C6), 66.9, 65.8, 59.9 (CH2 OEt), 55.8 (C2 or C2 ), 55.6
00
(C2 or C2 ), 33.8 (C11), 28.7 (C8 or C10), 25.2 (C9), 24.3 (C8
JH3 eH2 ¼3.2 Hz, JH3 eH4 ¼10.0 Hz, H3 ), 5.84 (t, 1H, JH4eH3
¼
0
0
0
0
JH4eH5¼10.1 Hz, H4), 5.70 (t, 1H, JH3 eH4 ¼JH3 eH2 ¼4.7 Hz,
0
0
00
H3 ), 5.62e5.59 (m, 2H, H2 , H2 ), 5.38 (dd, 1H, JH3eH4
¼
¼
¼
0
0
0
10.1 Hz, JH3eH2¼3.2 Hz, H3), 5.28 (d, 1H, JH1 eH2
or C10), 20.4 (CH3 OAc), 16.9 (C6 ), 14.1 (CH3 OEt). MS
3.0 Hz, H1 ), 5.17 (m, 1H, H4 ), 5.06 (d, 1H, JH1 eH2
FABþ-HRMS m/z [MþNa]þ calcd for C79H82N2O20Na
0
0
00
00
00
00
1.8 Hz, H1 ), 4.83 (s, 1H, H1), 4.82e4.60 (m, 2H, H2, H6a ),
1401.5359, found 1401.5370.
0
0
0
4.48 (dd, 1H, Jgem¼12.9 Hz, JH5a eH4 ¼2.9 Hz, H5a ), 4.46e
00
00
4.41 (m, 2H, H5 , H6b ), 4.03e3.93 (m, 2H, H5, H7a), 3.76
(dd, 1H, Jgem¼12.0 Hz, JH6aeH5¼7.1 Hz, H6a), 3.67 (dd, 1H,
Jgem¼12.8 Hz, JH6beH5¼2.6 Hz, H6b), 3.65 (s, 3H, OMe),
3.59 (dt, 1H, Jgem¼9.3 Hz, JH7beH8¼6.5 Hz, H7b), 3.42 (dd,
4.1.3. (2-Methyl-5-tert-butylphenyl) 2-O-benzoyl-3,4,6-
tri-O-benzyl-1-thio-b-D-glucopyranoside (3)
To a mixture of 14 (16.20 g, 26.47 mmol), DMAP (0.640 g,
5.294 mmol, 0.2 equiv) in anhydrous dichloromethane
(100 mL) were added at 0 ꢀC, under argon, triethylamine
(26.0 mL, 185.3 mmol, 7 equiv) and benzoyl chloride
0
0
0
1H, Jgem¼12.7 Hz, JH5b eH4 ¼2.9 Hz, H5b ), 2.20 (t, 2H,
JH11eH10¼7.8 Hz, H11), 1.69e1.52 (m, 2H, H8 or H10),

1528
M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
(9.22 mL, 79.41 mmol, 3 equiv). The mixture was heated with
stirring at 40 ꢀC for 12 h. The mixture was allowed to cool
down to room temperature, the product was extracted with di-
chloromethane, washed with HCl (1 M) and neutralised with
a saturated NaHCO3 solution. The organic layer was dried
over MgSO4, filtered and the solvent was evaporated. The res-
idue was purified by column chromatography on silica gel (cy-
clohexane/EtOAc 9:1) to give 18.10 g of 3 (95%) as a white
solid. Rf: 0.43 (cyclohexane/EtOAc 9:1). Mp: 72 ꢀC. [a]D25
31.2 (t-Bu), 20.2 (CH3). MS DCIþ-HRMS m/z [MþNH4]þ
calcd for C37H40NO7S 642.2524, found 642.2529.
4.1.5. (2-Methyl-5-tert-butylphenyl) 2,3,4,6-tetra-O-
benzoyl-1-thio-a-D-mannopyranoside (5)
Benzoyl chloride (17 mL, 146.6 mmol, 4.4 equiv) was
added dropwise to a cooled (0 ꢀC) solution of D-mannose
(5 g, 27.8 mmol, 1 equiv) in pyridine (30 mL). The reaction
mixture was stirred for 12 h at room temperature and concen-
trated. A solution of the residue in dichloromethane was
washed with aq HCl, water, a saturated NaHCO3 solution,
dried over MgSO4 and concentrated. The reside was
crystallised in ethanol to give pentabenzoyl a-D-mannopyr-
anose (18.5 g, 95%) To a solution of 1,2,3,4,6-penta-O-
benzoyl-D-mannopyranose (5.000 g, 7.142 mmol) in anhydrous
dichloromethane (10 mL), were added under argon, 2-methyl-
5-tert-butylthiophenol (1.97 mL, 10.71 mmol, 1.5 equiv) and
BF3$Et2O (4.52 mL, 35.71 mmol, 5 equiv). The mixture was
allowed to stir overnight and was neutralised with a saturated
NaHCO3 solution at 0 ꢀC. The product was extracted with
dichloromethane, the organic layer was dried over MgSO4,
filtered and the solvent was evaporated. The residue was puri-
fied by column chromatography on silica gel (cyclohexane/
EtOAc 9:1) to give 4.780 g of 5 (88%) as a white foam
containing 2 anomers (a/b 8.4:1). a anomer: Rf: 0.26 (cyclo-
1
ꢁ42 (c 1.5, CHCl3). H NMR (400 MHz, CDCl3) d: 8.19e
7.19 (m, 23H, H Ar), 5.51 (dd, 1H, JH2eH1¼10.0 Hz, JH2eH3
¼
9.0 Hz, H2), 4.96 (d, 1H, Jgem¼10.0 Hz, CHPh), 4.89 (d,
1H, JH1eH2¼10.0 Hz, H1), 4.87 (d, 1H, Jgem¼11.0 Hz,
CHPh), 4.81 (d, 1H, Jgem¼11.0 Hz, CHPh), 4.75 (d, 1H,
Jgem¼12.0 Hz, CHPh), 4.72 (d, 1H, Jgem¼11.0 Hz, CHPh),
4.70 (d, 1H, Jgem¼12.0 Hz, CHPh), 3.99 (t, 1H, JH3eH2
¼
JH3eH4¼9.0 Hz, H3), 3.88 (m, 1H, H4), 3.92 (m, 2H, H6a,
H6b), 3.73 (m, 1H, H5), 2.33 (s, 3H, CH3), 1.39 (s, 9H,
t-Bu). 13C NMR (100 MHz, CDCl3) d: 165.1 (CO Bz),
149.4e124.6 (30C, C Ar), 87.2 (C1), 84.2 (C3), 79.2 (C5),
77.6 (C4), 75.1 (CH2Ph), 74.9 (CH2Ph), 73.3 (CH2Ph), 72.4
(C2), 68.6 (C6), 34.2 (Cq t-Bu), 31.1 (t-Bu), 20.1 (CH3). MS
FABþ-HRMS m/z [MþNa]þ calcd for C45H48O6SNa
739.3069, found 739.3055.
1
4.1.4. (2-Methyl-5-tert-butylphenyl) 2,3,4-tri-O-benzoyl-1-
thio-b-D-xylopyranoside (4)
hexane/EtOAc 9:1). H NMR (400 MHz, CDCl3) d: 8.16e7.40
¼
(m, 23H, H Ar), 6.35 (t, 1H, JH3eH4¼10.1 Hz, JH4eH5
Benzoyl chloride (17.0 mL, 146.6 mmol, 4.4 equiv) was
added dropwise to a cooled (0 ꢀC) solution of D-xylose (5 g,
33.3 mmol, 1 equiv) in pyridine (30 mL). The reaction mixture
was stirred for 12 h at room temperature and concentrated. A
solution of the residue in dichloromethane was washed with aq
HCl, water and sodium hydrogen carbonate, dried over MgSO4
and concentrated. The residue was crystallised in ethanol
to give pentabenzoyl a,b-D-xylopyranose (16.0 g, 85%; a/b
85:15). To a solution of 1,2,3,4-tetra-O-benzoyl-D-xylopyranose
(2.000 g, 3.533 mmol, 1 equiv) in anhydrous dichloromethane
(23 mL), were added under argon, 2-methyl-5-tert-butyl-
thiophenol (0.973 mL, 5.30 mmol, 1.5 equiv) and BF3$Et2O
(2.20 mL, 17.66 mmol, 5 equiv). The mixture was allowed
to stir overnight and was neutralised with a saturated NaHCO3
solution at 0 ꢀC. The product was extracted with dichloro-
methane, the organic layer was dried over MgSO4, filtered
and the solvent was evaporated. The residue was purified by
column chromatography on silica gel (cyclohexane/EtOAc
7:3) to give 1.870 g of 4 (85%) as a white foam containing
2 anomers (a/b 8:92). Rf: 0.42 (cyclohexane/EtOAc 7:3).
b anomer: 1H NMR (400 MHz, CDCl3) d: 8.08e7.40 (m,
18H, H Ar), 5.88 (t, 1H, JH3eH2¼JH3eH4¼6.5 Hz, H3), 5.63
10.0 Hz, H4), 6.12 (dd, 1H, JH2eH3¼3.2 Hz, JH2eH1¼1.6 Hz,
H2), 6.04 (dd, 1H, JH3eH4¼10.1 Hz, JH2eH3¼3.2 Hz, H3),
5.80 (d, 1H, JH1eH2¼1.6 Hz, H1), 4.78 (dd, 1H, JH6aeH6b
¼
¼
12.0 Hz, JH5eH6a¼2.6 Hz, H6a), 4.64 (dd, 1H, JH6aeH6b
12.0 Hz, JH5eH6b¼3.7 Hz, H6b), 2.58 (s, 3H, CH3), 1.47 (s,
9H, t-Bu). 13C NMR (100 MHz, CDCl3) d: 166.0 (CO Bz),
165.4 (CO Bz), 165.3 (CO Bz), 165.2 (CO Bz), 149.9e
123.0 (30C, C Ar), 86.0 (C1), 72.3 (C2), 70.4 (C3), 70.1
(C5), 66.8 (C4), 62.7 (C6), 34.3 (Cq t-Bu), 31.2 (3C, t-Bu),
20.4 (CH3). MS DCIþ-HRMS m/z [MþNH4]þ calcd for
C45H46NO9S 776.2893, found 776.2896.
4.1.6. (2-Methyl-5-tert-butylphenyl) 3,4,6-tri-O-acetyl-2-
deoxy-2-phthalimido-1-thio-b-D-glucopyranoside (6)
To a mixture of 1,3,4,6-tetra-O-acetyl-2-deoxy-2-phthal-
imido-D-glucopyranose 15 (4.010 g, 8.400 mmol) and 2-
methyl-5-tert-butylthiophenol (2.32 mL, 12.61 mmol, 1.5 equiv)
in anhydrous dichloromethane under argon was added
BF3$Et2O (5.33 mL, 25.20 mmol, 5 equiv). The mixture was
stirred overnight at room temperature and excess BF3$Et2O
was neutralised with a saturated NaHCO3 solution at 0 ꢀC.
The product was extracted with dichloromethane. The organic
layer was dried over MgSO4, filtered and the solvent was evap-
orated. The residue was purified by column chromatography
on silica gel (cyclohexane/EtOAc 7:3) to give 4.95 g of 6
(98%) as a white solid. Rf: 0.61 (cyclohexane/EtOAc 5:5).
(t, 1H, JH2eH3¼JH2eH1¼6.5 Hz, H2), 5.41 (ddd, 1H, JH4eH3
¼
6.5 Hz, JH4eH5b¼7.0 Hz, JH4eH5a¼4.0 Hz, H4), 5.54 (d, 1H,
JH1eH2¼6.5 Hz, H1), 4.80 (dd, 1H, Jgem¼12.1 Hz, JH5aeH4
¼
4.0 Hz, H5a), 3.87 (dd, 1H, Jgem¼12.1 Hz, JH5beH4¼7.0 Hz,
H5b), 2.42 (s, 3H, CH3), 1.37 (s, 9H, t-Bu). 13C NMR
(100 MHz, CDCl3) d: 165.4 (CO Bz), 165.1 (CO Bz), 165.0
(CO Bz), 149.4e124.6 (24C, C Ar), 86.8 (C1), 70.6 (C3),
70.2 (C5), 77.6 (C2), 68.7 (C4), 63.6 (C5), 34.3 (Cq t-Bu),
1
Mp: 69 ꢀC. [a]D25 þ54 (c 1.1, CHCl3). H NMR (400 MHz,
CDCl3) d: 7.86 (br m, 2H, H Phth), 7.75 (m, 2H, H Phth),
7.47 (d, 1H, Jaec¼1.9 Hz, Ha), 7.21 (dd, 1H, Jceb¼8.0 Hz,
Hc), 7.06 (d, 1H, Hb), 5.82 (dd, 1H, JH3eH2¼JH3eH4
¼

M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1529
9.7 Hz, H3), 5.65 (d, 1H, JH1eH2¼10.6 Hz, H1), 5.20 (dd, 1H,
JH4eH5¼9.6 Hz, H4), 4.42 (dd, 1H, H2), 4.34 (dd, 1H,
evaporated. The residue was purified by column chromatogra-
phy on silica gel (cyclohexane/EtOAc 7:3) to give 1.60 g of 8
(93%) as a white solid. Rf: 0.47 (cyclohexane/EtOAc 7:3). Mp:
Jgem¼12.3 Hz, JH6eH5¼4.6 Hz, H6), 4.16 (dd, 1H, JH6eH5
¼
1
1.9 Hz, H6), 3.88 (m, 1H, H5), 2.15 (s, 3H, CH3), 2.09 (s,
3H, CH3 OAc), 2.01 (s, 3H, CH3 OAc), 1.84 (s, 3H, CH3
OAc), 1.27 (s, 9H, t-Bu). 13C NMR (100 MHz, CDCl3) d:
170.4 (CO OAc), 169.8 (CO OAc), 169.1 (CO OAc), 167.5
(CO Phth), 166.7 (CO Phth), 149.3, 137.4, 134.2, 134.1,
131.3, 130.9, 130.8, 130.2, 129.8, 125.5, 123.5, 123.4 (C Ar),
84.1 (C1), 75.6 (C5), 71.4 (C3), 68.4 (C4), 62.0 (C6), 53.5
(C2), 34.1 (Cq t-Bu), 31.0 (t-Bu), 20.5 (CH3), 20.4 (CH3),
20.2 (CH3), 20.0 (CH3). MS FABþ-HRMS m/z [MþNa]þ
calcd for C31H35NO9SNa 620.1930, found 620.1935.
173e174 ꢀC. [a]D25 þ46 (c 1.1, CHCl3). H NMR (400 MHz,
CDCl3) d: 8.00e7.20 (m, 12H, H Ar), 5.99 (dd, 1H, JH3eH2
¼
JH3eH4¼9.4 Hz, H3), 5.81 (d, 1H, JH1eH2¼10.6 Hz, H1), 5.61
(s, 1H, H benzylidene), 4.49 (dd, 1H, H2), 4.45 (dd,
1H, Jgem¼10.1 Hz, JH6eH5¼4.2 Hz, H6), 3.95e3.80 (m, 3H,
0
H4, H5, H6 ), 2.21 (s, 3H, CH3 thio), 1.94 (s, 3H, CH3 OAc),
1.33 (s, 9H, t-Bu). 13C NMR (100 MHz, CDCl3) d:
170.0 (CO OAc), 167.6 (CO Phth), 167.1 (CO Phth),
149.5e123.5 (C Ar), 101.5 (C benzylidene), 84.6 (C1), 79.0,
70.5 (C3), 70.3, 68.5 (C6), 54.3 (C2), 34.3 (Cq t-Bu), 31.1
(t-Bu), 20.5 (CH3 OAc), 20.1 (CH3 thio). MS DCIþ-HRMS
m/z [MþNH4]þ calcd for C34H39N2O7S 619.2478, found
619.2474.
4.1.7. (2-Methyl-5-tert-butylphenyl) 2,3,4-tri-O-benzyl-
1-thio-b-L-fucopyranoside (7)
Compound 17 (19.21 g, 41.04 mmol) was dissolved in an-
hydrous methanol (80 mL) under argon. Sodium (0.188 g,
0.2 equiv) was added. After 45 min, the mixture was neutral-
ised (IR 120Hþ), filtered and the solvent was evaporated to
give a white foam. [Rf: 0.55 (dichloromethane/methanol
9:1)]. The crude product was dissolved in anhydrous DMF
(140 mL) under argon and benzyl bromide was added
(3.91 mL, 117.1 mmol, 3.5 equiv). The mixture was cooled
at 0 ꢀC and NaH (60% dispersion in mineral oil, 5.35 g,
133.8 mmol, 4 equiv) was added slowly portionwise. The mix-
ture allowed warming up to room temperature overnight. The
excess benzyl bromide and NaH was quenched with methanol.
The solvent was evaporated and the residue was purified by
column chromatography on silica gel (cyclohexane/EtOAc
95:5) to give 17.33 g of 7 (84%, b anomer only) as a white
solid. Rf: 0.46 (cyclohexane/EtOAc 9:1). Mp: 62e63 ꢀC.
4.1.9. (2-Methyl-5-tert-butylphenyl) 3-O-benzyl-4,6-
O-benzylidene-2-deoxy-2-phthalimido-1-thio-
b-D-glucopyranoside (9)
Compound 18 (1.000 g, 1.788 mmol) was dissolved in an-
hydrous THF (10 mL) under argon. Benzyl bromide (0.32 mL,
2.680 mmol, 1.5 equiv) was added and NaH (60% dispersion
in mineral oil, 0.085 g, 3.576 mmol, 2.0 equiv) was added
slowly portionwise. The mixture was then heated at reflux
for 3 h, after this time, the mixture was allowed to cool
down at room temperature and the excess benzyl bromide
and NaH was destroyed with methanol. The solvents were
evaporated. The product was extracted with dichloromethane
and washed with water. The organic layer was dried over
MgSO4, filtered and evaporated. The residue was purified by
column chromatography on silica gel (cyclohexane/EtOAc
8:2) to give 0.731 g of 9 (63%) as a white foam. Rf: 0.66 (cy-
1
[a]2D5 þ1.6 (c 2.1, CHCl3). H NMR (400 MHz, CDCl3) d:
1
7.99e7.32 (m, 18H, H Ar), 5.22 (d, 1H, Jgem¼11.8 Hz,
CHPh), 5.13 (d, 1H, Jgem¼10.3 Hz, CHPh), 5.05 (d, 1H,
Jgem¼10.3 Hz, CHPh), 4.96 (m, 3H, 3CHPh), 4.82 (d, 1H,
JH1eH2¼9.8 Hz, H1), 4.20 (dd, 1H, JH1eH2¼JH2eH3¼9.8 Hz,
H2), 3.85 (d, 1H, JH4eH3¼2.7 Hz, H4), 3.80 (dd, 1H, H3), 3.69
(q, 1H, JH5eH6¼6.3 Hz, H5), 2.63 (s, 3H, CH3 thio), 1.50 (s,
9H, t-Bu), 1.46 (d, 3H, J¼6.3 Hz, H6). 13C NMR (100 MHz,
CDCl3) d: 148.9 (Cq Ar), 138.3 (Cq Ar), 138.2 (Cq Ar), 138.1
(Cq Ar), 135.4 (Cq Ar), 133.5 (Cq Ar), 129.4e123.8 (C Ar),
87.7 (C1), 84.4 (C3), 77.3 (C2), 76.0 (C4), 75.4 (CHPh), 74.3
(CHPh), 74.2 (C5), 72.7 (CHPh), 34.2 (Cq t-Bu), 31.0
(t-Bu), 20.1 (CH3 thio), 17.1 (C6). MS FABþ-HRMS m/z
[MþNa]þ calcd for C38H44O4SNa 619.2859, found 619.2862.
clohexane/EtOAc 7:3). [a]2D5 þ57 (c 1.9, CHCl3). H NMR
(400 MHz, CDCl3) d: 7.56e6.91 (17H, H Ar), 5.68 (s, 1H,
H benzylidene), 5.59 (d, 1H, JH1eH2¼10.5 Hz, H1), 4.83 (d,
1H, Jgem¼12.3 Hz, CHPh), 4.57e4.38 (m, 4H, CHPh, H2,
0
H4, H6), 3.94 (m, 2H, H3, H6 ), 3.74 (m, 1H, H5), 2.15 (s, 3H,
CH3), 1.30 (s, 9H, t-Bu). 13C NMR (100 MHz, CDCl3) d:
149e123 (C Ar), 101.7 (C benzylidene), 85.2 (C1), 83.3 (C3),
75.9 (C4), 74.6 (CHPh), 70.7 (C5), 69.1 (C6), 55.3 (C2), 34.8 (Cq
t-Bu), 31.6 (t-Bu), 20.5 (CH3). MS DCIþ-HRMS m/z
[MþNH4]þ calcd for C39H43N2O6S 667.2842, found 667.2836.
4.1.10. (2-Methyl-5-tert-butylphenyl) 4,6-O-benzylidene-
3-O-tert-butyldimethylsilyl-2-deoxy-2-phthalimido-1-thio-
b-D-glucopyranoside (10)
4.1.8. (2-Methyl-5-tert-butylphenyl) 3-O-acetyl-4,6-
O-benzylidene-2-deoxy-2-phthalimido-1-thio-b-D-
glucopyranoside (8)
To a solution of 18 (1.600 g, 2.857 mmol) in anhydrous
pyridine (10 mL) was added acetic anhydride (0.9 mL) under
argon and the mixture was allowed to stir overnight. The sol-
vents were evaporated and the residue was extracted with
dichloromethane, washed with an aq HCl solution (1 M) and
neutralised with a saturated NaHCO3 solution. The organic
layer was dried over MgSO4, filtered and the solvent was
Compound 18 (3.080 g, 5.510 mmol) was dissolved in anhy-
drous pyridine (6 mL) and TBDMSOTf (2.53 mL, 11.02 mmol,
2 equiv) was added at room temperature under argon. The
mixture was stirred for 1 h, the solvent was evaporated and
the residue was extracted with dichloromethane, washed with
a HCl solution (1 M) and neutralised with a saturated NaHCO3
solution. The organic layer was dried over MgSO4, filtered
and the solvent was evaporated. The residue was purified by
column chromatography on silica gel (cyclohexane/EtOAc
9:1) to give 3.49 g of 10 (94%) as a white foam. Rf: 0.44

1530
M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
(cyclohexane/EtOAc 9:1). [a]2D5 þ51 (c 2.4, CHCl3). 1H NMR
(400 MHz, CDCl3) d: 8.00e7.07 (m, 12H, H Ar), 5.63 (d, 1H,
JH1eH2¼10.7 Hz, H1), 5.60 (s, 1H, H benzylidene), 4.74 (dd,
1H, JH3eH4¼JH3eH2¼9.0 Hz, H3), 4.46 (dd, 1H, H2), 4.41
(dd, 1H, Jgem¼10.4 Hz, JH6eH5¼4.8 Hz, H6), 3.90 (dd, 1H,
0
argon. Sodium (0.059 g, 2.565 mmol, 0.5 equiv) was added.
After 12 h, the mixture was neutralised (IR 120Hþ), filtered
and the solvent was evaporated. The residue was purified by
column chromatography on silica gel (cyclohexane/EtOAc
9:1) to give 2.580 g of 14 (82%) as a white solid. Rf: 0.4 (cy-
clohexane/EtOAc 9:1). Mp: 94 ꢀC. [a]D25 ꢁ24 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3) d: 7.83e7.27 (m, 18H, H Ar),
Jgem¼10.4 Hz, JH6eH5¼10.0 Hz, H6 ), 3.75 (ddd, 1H, JH5eH4
¼
9.2 Hz, H5), 3.68 (dd, 1H, H4), 2.18 (s, 3H, CH3 thio), 1.32 (s,
9H, t-Bu), 0.65 (s, 9H, t-Bu TBS), ꢁ0.06 (s, 3H, CH3 TBS),
ꢁ0.23 (s, 3H, CH3 TBS). 13C NMR (100 MHz, CDCl3) d:
168.2, 167.3 (CO Phth), 149.0e123.0 (C Ar), 101.9 (C benzyl-
idene), 85.0 (C1), 82.5 (C4), 70.6 (C3), 70.3 (C5), 68.6 (C6),
56.8 (C2), 34.3 (Cq t-Bu), 31.1 (t-Bu), 25.3 (t-Bu TBS), 20.1
(CH3 thio), 17.6 (Cq t-Bu TBS), ꢁ4.2 (CH3 TBS), ꢁ5.3
(CH3 TBS). MS DCIþ-HRMS m/z [MþNH4]þ calcd for
C38H51N2O6SSi 691.3237, found 691.3232.
5.10 (d, 1H, Jgem¼11.0 Hz, CHPh), 5.00 (d, 1H, Jgem
¼
11.0 Hz, CHPh), 4.99 (d, 1H, Jgem¼10.0 Hz, CHPh), 4.76e
4.69 (m, 3H, CHPh), 4.68 (d, 1H, JH1eH2¼12.0 Hz, H1),
3.92e3.85 (m, 2H, H6a, H6b), 3.81e3.73 (m, 3H, H4, H3,
H2), 3.67 (m, 1H, H5), 2.68 (d, 1H, JOHeH2¼1.5 Hz, OH C2),
2.56 (s, 3H, CH3), 1.43 (s, 9H, t-Bu). 13C NMR (100 MHz,
CDCl3) d: 149.4e124.7 (24C, C Ar), 88.6 (C1), 85.9 (C2),
78.1 (C5), 77.3 (C4), 75.1 (CH2Ph), 74.9 (CH2Ph), 73.3
(CH2Ph), 72.9 (C3), 68.7 (C6), 34.3 (Cq t-Bu), 31.1 (t-Bu),
20.3 (CH3). MS FABþ-HRMS m/z [MþK]þ calcd for
C38H44O5SK 651.2547, found 651.2535.
4.1.11. (2-Methyl-5-tert-butylphenyl) 2-O-acetyl-3,4,6-
tri-O-benzyl-1-thio-b-D-glucopyranoside (12)
To a mixture of 1,2-O-(1-ethoxyethylene) 3,4,6-O-benzyl-
b-D-glucopyranose 11 (0.490 g, 0.970 mmol) and 2-methyl-
5-tert-butylthiophenol (0.356 mL, 1.940 mmol, 2 equiv) in
anhydrous toluene (5 mL) was added under argon, mercury
bromide (0.035 g, 0.097 mmol, 0.1 equiv). The mixture was
stirred at 80 ꢀC overnight and the solvent was evaporated.
The residue was purified by column chromatography on silica
gel (cyclohexane/EtOAc 9:1) to give 410 mg of 12 (64%) as
a white foam. Rf: 0.40 (cyclohexane/EtOAc 9:1). Alternative
preparation: A solution of the 1,2-O-(1-ethoxyethylene)
3,4,6-O-benzyl-b-D-glucopyranose 11 (10.6 g, 20.98 mmol)
in acetic acid (20 mL) was stirred for 30 min at room temper-
ature and was concentrated. 2-Methyl-5-tert-butylthiophenol
(4.63 mL, 25.18 mmol, 1.2 equiv) and BF3$Et2O (5.3 ml,
41.96 mmol, 2 equiv) were added to a solution of the residue
in toluene (20 mL). The solution was stirred for 2 h, neutral-
ised with aq hydrogen carbonate (200 mL) and diluted with
dichloromethane. The organic layer was separated, dried over
MgSO4 and concentrated. The residue was purified by column
chromatography on silica gel to give 8.9 g of 12 (65%). [a]D25
þ15 (c 2.2, CHCl3). 1H NMR (400 MHz, CDCl3) d: 8.29e7.30
(m, 18H, H Ar), 5.38 (t, 1H, JH2eH1¼JH2eH3¼10.0 Hz, H2),
5.04 (d, 1H, Jgem¼11.4 Hz, CHPh), 5.02 (d, 1H, Jgem¼10.7 Hz,
CHPh), 4.92 (d, 1H, Jgem¼10.7 Hz, CHPh), 4.83 (d, 1H, H1),
4.78 (d, 1H, Jgem¼10.7 Hz, CHPh), 4.76 (d, 1H, Jgem¼12.7 Hz,
CHPh), 4.72 (d, 1H, Jgem¼12.7 Hz, CHPh), 3.99e3.95 (m, 3H,
H4, H6a, H6b), 3.94 (t, 1H, JH3eH2¼JH3eH4¼10.0 Hz, H3), 3.73
(m, 1H, H5), 2.69 (s, 3H, CH3 thio), 2.20 (s, 3H, CH3 OAc),
1.52 (s, 9H, t-Bu). 13C NMR (100 MHz, CDCl3) d: 169.0
(CO OAc), 149.2e124.3 (24C, C Ar), 86.5 (C1), 84.1 (C3),
78.9 (C5), 77.4 (C4), 74.8 (CH2Ph), 73.6 (CH2Ph), 73.0
(CH2Ph), 71.5 (C2), 68.3 (C6), 34.0 (Cq t-Bu), 30.9 (t-Bu),
20.5 (CH3 OAc), 19.9 (CH3 thio). MS DCIþ m/z [MþNH4]þ
calcd for C40H50NO6S 672.3, found 672.3.
4.1.13. (2-Methyl-5-tert-butylphenyl) 2,3,4-tri-O-acetyl-
1-thio-L-fucopyranoside (17)
To a mixture of 1,2,3,4-tetra-O-acetyl-L-fucopyranose 16
(10.30 g, 30.48 mmol) in anhydrous dichloromethane
(60 mL) under argon, were added, 2-methyl-5-tert-butylthio-
phenol (8.35 mL, 45.72 mmol, 1.5 equiv) and BF3$Et2O
(19.3 mL, 152.4 mmol, 5 equiv). The mixture was allowed to
stir overnight and was neutralised with a saturated NaHCO3
solution at 0 ꢀC. The product was extracted with dichlorome-
thane. The organic layer was dried over MgSO4, filtered and
the solvent was evaporated. The residue was purified by col-
umn chromatography on silica gel (cyclohexane/EtOAc 2:1)
to give 13.36 g of 17 (97%) as a white foam consisting of 2
anomers (a/b 1:7). a anomer: Rf: 0.47 (cyclohexane/EtOAc
2:1). [a]2D5 ꢁ143 (c 1.7, CHCl3). 1H NMR (400 MHz,
CDCl3) d: 7.52e7.17 (3H, H Ar), 5.90 (m, 1H, H1), 5.38
(m, 3H, H2, H3, H4), 4.69 (q, 1H, JH5eH6¼6.6 Hz, H5), 2.39
(s, 3H, CH3 thio), 2.21 (s, 3H, CH3 OAc), 2.14 (s, 3H, CH3
OAc), 2.06 (s, 3H, CH3 OAc), 1.32 (s, 9H, t-Bu), 1.18 (d,
3H, J¼6.6 Hz, H6). 13C NMR (100 MHz, CDCl3) d: 170.5
(CO OAc), 170.2 (CO OAc), 169.5 (CO OAc), 149.6 (Cq
Ar), 136.4 (Cq Ar), 132.0 (Cq Ar), 129.9 (C Ar), 129.5 (C
Ar), 124.7 (C Ar), 85.0 (C1), 70.9, 68.5, 68.2 (C2, C3, C4),
65.5 (C5), 34.4 (Cq t-Bu), 31.2 (t-Bu), 20.8 (CH3 OAc), 20.7
(CH3 OAc), 20.6 (CH3 OAc), 20.0 (CH3 thio), 15.8 (C6).
MS DCIþ-HRMS m/z [MþNH4]þ calcd for C23H36NO7S
470.2212, found 470.2207. b anomer: Rf: 0.54 (cyclohexane/
1
EtOAc 2:1). [a]2D5 ꢁ10 (c 3.4, CHCl3). H NMR (400 MHz,
CDCl3) d: 7.64, 7.24, 7.16 (H Ar), 5.31 (m, 2H, H2, H4),
5.09 (dd, 1H, JH3eH2¼9.0 Hz, JH3eH4¼3.4 Hz, H3), 4.67 (d,
1H, JH1eH2¼10.0 Hz, H1), 3.85 (qd, 1H, JH5eH4¼1.0 Hz,
JH5eH6¼6.7 Hz, H5), 2.39 (s, 3H, CH3 thio), 2.21 (s, 3H,
OAc), 2.13 (s, 3H, OAc), 2.02 (s, 3H, OAc), 1.34 (s, 9H,
t-Bu), 1.28 (d, 3H, J¼6.7 Hz, H6). 13C NMR (100 MHz,
CDCl3) d: 170.6 (CO OAc), 170.0 (CO OAc), 169.5 (CO
OAc), 149.4 (Cq Ar), 136.5 (Cq Ar), 132.3 (Cq Ar), 129.8
(CH Ar), 129.7 (CH Ar), 125.1 (CH Ar), 86.9 (C1), 73.0
(C5), 72.3 (C3), 70.2 (C4), 67.4 (C2), 34.3 (Cq t-Bu), 31.2
4.1.12. (2-Methyl-5-tert-butylphenyl) 3,4,6-tri-O-benzyl-
1-thio-b-D-glucopyranoside (14)
Compound 12 (3.370 g, 5.153 mmol) was dissolved in an-
hydrous methanol (25 mL) and anhydrous THF (5 mL) under

M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1531
(t-Bu), 20.7 (CH3 OAc), 20.6 (CH3 OAc), 20.5 (CH3 OAc),
20.1 (CH3 thio), 16.4 (C6).
173.1 (CO COOEt), 169.0 (CO Bz), 137.8e127.2 (24C, C
Ar), 100.8 (C1), 82.3 (C3), 76.6 (C4), 74.8 (C5), 74.6
(CH2Ph), 74.6 (CH2Ph), 73.5 (C2), 73.1 (CH2Ph), 69.0 (C7),
68.4 (C6), 59.7 (CH2 OEt), 33.6 (C11), 28.7 (C8 or C10), 25.0
(C9), 24.1 (C8 or C10), 13.9 (CH3 OEt). MS FABþ-HRMS m/z
[MþNa]þ calcd for C42H48O9Na 719.3196, found 719.3190.
4.1.14. (2-Methyl-5-tert-butylphenyl) 4,6-O-benzylidene-
2-deoxy-2-phthalimido-1-thio-b-D-glucopyranoside (18)
Compound 6 (2.000 g, 3.35 mmol) was dissolved in anhy-
drous methanol (10 mL) and anhydrous THF (3 mL) under ar-
gon. Sodium (0.015 g, 0.670 mmol, 0.2 equiv) was added.
After 2 h, the mixture was neutralised (IR 120Hþ), filtered
and the solvent was evaporated to give a white foam. [Rf:
0.46 (dichloromethane/methanol 9:1)]. The crude product
was dissolved in anhydrous acetonitrile (60 mL) under argon.
To the solution was added successively: benzaldehyde di-
methyl acetal (1.00 mL, 6.700 mmol, 2 equiv) and camphor-
sulphonic acid (0.232 g, 1.000 mmol, 0.3 equiv). After 1 h
a saturated NaHCO3 solution was added and the product
was extracted with dichloromethane. The organic layer was
dried over MgSO4, filtered and the solvent was evaporated.
The residue was purified by column chromatography on silica
gel (cyclohexane/EtOAc 7:3) to give 1.69 g of 18 (90%) as
a white solid. Rf: 0.29 (cyclohexane/EtOAc 7:3). Mp:
104 ꢀC. [a]D25 þ46 (c 1.2, CHCl3). 1H NMR (400 MHz,
CDCl3) d: 8.00e7.09 (m, 12H, H Ar), 5.62 (m, 2H, H1, H benz-
4.1.16. 5-Methoxycarbonylpentyl 3,4,6-tri-O-benzyl-
b-D-glucopyranoside (20)
Compound 19 (1.820 g, 2.615 mmol) was dissolved in an-
hydrous methanol (15 mL) under argon. Sodium (0.030 g,
1.307 mmol, 0.5 equiv) was added. The mixture was heated
at 60 ꢀC for 2 h, allowed to cool down to room temperature,
neutralised (IR 120Hþ), filtered and the solvent was evapo-
rated. The residue was purified by column chromatography
on silica gel (cyclohexane/EtOAc 8:2) to give 1.350 g of 20
(89%) as a white solid. Rf: 0.40 (cyclohexane/EtOAc 8:2).
1
Mp: 39 ꢀC. [a]D25 ꢁ9 (c 0.7, CHCl3). H NMR (400 MHz,
CDCl3) d: 7.46e7.22 (m, 15H, H Ar), 5.04 (d, 1H,
Jgem¼11.3 Hz, CHPh), 4.92 (m, 2H, CHPh), 4.71 (d, 1H,
Jgem¼12.0 Hz, CHPh), 4.60 (d, 1H, Jgem¼12.0 Hz, CHPh),
4.59 (d, 1H, Jgem¼10.8 Hz, CHPh), 4.31 (d, 1H, JH1eH2
¼
7.3 Hz, H1), 4.00 (m, 1H, H7a), 3.88e3.74 (m, 2H, H6a, H6b),
3.72 (s, 3H, OMe), 3.67 (dd, 1H, J¼8.1, 5.6 Hz, H3), 3.64e
3.53 (m, 4H, H7b, H5, H4, H2), 2.68 (d, 1H, JOHeH2¼2.0 Hz,
OH C2), 2.28 (t, 2H, JH11eH10¼7.0 Hz, H11), 1.78e1.66 (m,
4H, H10, H8), 1.37e1.24 (m, 2H, H9). 13C NMR (100 MHz,
CDCl3) d: 174.1 (CO COOMe), 137.9e127.5 (18C, C Ar),
102.6 (C1), 84.4 (C3), 77.4 (C2), 75.0 (CH2Ph), 74.9
(CH2Ph), 74.9 (C5), 74.6 (C4), 73.3 (CH2Ph), 69.5 (C7), 68.7
(C6), 51.4 (OMe), 33.7 (C11), 28.9 (C8 or C10), 25.4 (C9),
24.4 (C8 or C10). MS DCIþ-HRMS m/z [MþNH4]þ calcd
for C34H46NO8 596.3223, found 596.3217.
ylidene), 4.67 (m, 1H, H3), 4.42 (dd, 1H, JH2eH1¼JH2eH3
¼
0
10.4 Hz, H2), 4.39 (m, 1H, H6), 3.89 (m, 1H, H6 ), 3.66 (m,
2H, H4, H5), 2.89 (d, 1H, JOHeH3¼3.6 Hz, OH), 2.20 (s, 3H,
CH3), 1.32 (s, 9H, t-Bu). 13C NMR (100 MHz, CDCl3) d:
168.1, 167.5 (CO Phth), 149.4, 136.8, 134.1e128.1 (C Ar),
101.8 (C benzylidene), 85.0 (C1), 81.8 (C4), 70.1 (C5), 69.5
(C3), 68.5 (C6), 55.6 (C2), 34.3 (Cq t-Bu), 31.1 (t-Bu), 20.1
(CH3). MS DCIþ-HRMS m/z [MþNH4]þ calcd for
C32H37N2O6S 577.2372, found 577.2377.
4.1.15. 5-Ethoxycarbonylpentyl 2-O-benzoyl-3,4,6-
tri-O-benzyl-b-D-glucopyranoside (19)
To a mixture of 3 (0.192 g, 0.268 mmol), ethyl 6-hydroxy-
4.1.17. 5-Methoxycarbonylpentyl 3,4,6-tri-O-benzyl-
b-D-mannopyranoside (22)
˚
hexanoate (0.052 mL, 0.321 mmol, 1.2 equiv) and 4 A mole-
To a solution of oxalyl chloride (3.66 mL, 42.62 mmol,
3 equiv) in anhydrous dichloromethane (20 mL), cooled at
ꢁ78 ꢀC, was added dropwise DMSO (6.0 mL, 85.25 mmol,
6 equiv) under argon. After 15 min, a solution of 20
(8.213 g, 14.20 mmol, 1 equiv) in dichloromethane (20 mL)
was added dropwise and the mixture was left stirring for a fur-
ther 45 min at ꢁ78 ꢀC. Triethylamine (12.0 mL, 85.25 mmol,
6 equiv) was then added dropwise and the mixture was al-
lowed to warm up to room temperature. After 30 min the mix-
ture was extracted with dichloromethane and washed with
water. The organic layer was dried over MgSO4, filtered,
and an equivalent volume of methanol was poured into the so-
lution. Sodium borohydride (2.148 g, 56.83 mmol, 4 equiv)
was then added. The mixture was left stirring overnight at
room temperature and the solvents were evaporated. The
residue was purified by column chromatography on silica gel
(cyclohexane/EtOAc 7:3) to give 6.140 g of 22 (74%) as
a syrup. Rf: 0.35 (cyclohexane/EtOAc 7:3). [a]2D5 ꢁ15 (c 2.0,
cular sieves (200 mg) in anhydrous dichloromethane (3 mL)
were added under argon, NIS (0.122 g, 0.536 mmol, 2 equiv)
and TfOH (0.005 mL, 0.053 mmol, 0.2 equiv). The mixture
was stirred for 5 min and was then filtered, extracted with
dichloromethane and washed with saturated Na2S2O3 and
NaHCO3 solutions. The organic layer was dried over MgSO4,
filtered and the solvent was evaporated. The residue was puri-
fied by column chromatography on silica gel (cyclohexane/
EtOAc 9:1) to give 182 mg of 19 (97%) as a syrup. Rf: 0.43
(cyclohexane/EtOAc 8:2). [a]2D5 þ21 (c 1.3, CHCl3). 1H
NMR (400 MHz, CDCl3) d: 8.14e7.19 (m, 20H, H Ar), 5.42
(t, 1H, JH2eH1¼JH2eH3¼8.0 Hz, H2), 4.92 (d, 1H, Jgem
¼
11.0 Hz, CHPh), 4.85 (d, 1H, Jgem¼11.0 Hz, CHPh), 4.78 (d,
1H, Jgem¼11.0 Hz, CHPh), 4.73 (d, 1H, Jgem¼11.0 Hz,
CHPh), 4.68 (d, 1H, Jgem¼11.0 Hz, CHPh), 4.65 (d, 1H,
Jgem¼11.0 Hz, CHPh), 4.62 (d, 1H, H1), 4.13 (q, 2H,
J¼7.0 Hz, CH2 OEt), 4.01e3.82 (m, 5H, H7a, H6a, H6b, H4,
H3), 3.68 (m, 1H, H5), 3.57 (m, 1H, H7b), 2.08 (m, 2H, H11),
1.66e1.47 (m, 4H, H10, H8), 1.37e1.24 (m, 2H, H9), 1.30 (t,
3H, J¼7.0 Hz, CH3 OEt). 13C NMR (100 MHz, CDCl3) d:
1
CHCl3). H NMR (400 MHz, CDCl3) d: 7.42e7.27 (m, 15H,
H Ar), 4.95 (d, 1H, Jgem¼10.8 Hz, CHPh), 4.82 (d, 1H,
Jgem¼11.8 Hz, CHPh), 4.69 (d, 1H, Jgem¼11.5 Hz, CHPh),

1532
M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
4.67e4.59 (m, 3H, CHPh), 4.44 (s, 1H, H1), 4.14 (br s, 1H,
H2), 3.99 (dt, 1H, Jgem¼9.4 Hz, JH7aeH8¼6.6 Hz, H7a), 3.94
(800 mg) was added. The mixture was stirred at room temper-
ature overnight under H2 (1.2 bar). The mixture was filtered
off Celite and the solvent was evaporated. The residue was pu-
rified by column chromatography on silica gel (EtOAc) to give
1.060 g of 24 (92%) as a white foam. Rf: 0.44 (EtOAc). Mp:
(t, 1H, JH4eH5¼JH4eH3¼9.5 Hz, H4), 3.84 (dd, 1H, Jgem
¼
10.8 Hz, JH6aeH5¼2.1 Hz, H6a), 6.78 (dd, 1H, Jgem¼10.8 Hz,
JH6beH5¼5.0 Hz, H6b), 3.68 (s, 3H, OMe), 3.64 (d, 1H, JH3eH4
¼
1
9.1 Hz, H3), 3.55 (dt, 1H, Jgem¼9.4 Hz, JH7beH8¼6.9 Hz,
H7b), 3.48 (m, 1H, H5), 2.69 (s, 1H, OH C2), 2.35 (t, 2H,
JH11eH10¼7.4 Hz, H11), 2.48e1.67 (m, 4H, H10, H8), 1.48e
1.40 (m, 2H, H9). 13C NMR (100 MHz, CDCl3) d: 173.5
(CO COOMe), 137.8e127.0 (18C, C Ar), 99.3 (C1), 81.1
(C3), 74.8 (C5), 74.6 (CH2Ph), 73.8 (C4), 72.9 (CH2Ph), 70.7
(CH2Ph), 68.9 (C7), 68.8 (C6), 67.7 (C2), 50.9 (OMe), 33.4
(C11), 28.7 (C8 or C10), 25.1 (C9), 24.2 (C8 or C10). MS
DCIþ-HRMS m/z [MþNH4]þ calcd for C34H46NO8
596.3223, found 596.3223.
67e69 ꢀC. [a]D25 ꢁ25 (c 1.0, CHCl3). H NMR (400 MHz,
0
0
CDCl3) d: 8.04e7.27 (m, 15H, H Ar), 5.95 (dd, 1H, JH3 eH2
¼
0
0
0
0
0
8.9 Hz, JH3 eH4 ¼9.0 Hz, H3 ), 5.55 (dd, 1H, JH2 eH1 ¼7.0 Hz,
0
0
0
0
0
0
H2 ), 5.47 (dt, 1H, JH4 eH3 ¼9.0 Hz, JH4 eH5a ¼5.1 Hz, H4 ),
0
0
0
5.13 (d, 1H, H1 ), 4.53 (dd, 1H, Jgem¼12.1 Hz, JH4 eH5a
¼
0
5.1 Hz, H5a ), 4.43 (s, 1H, H1), 4.19 (s, 1H, H2), 3.87 (m,
0
1H, H4), 3.81e3.56 (m, 4H, H7a, H7b, H5b , H3), 3.70 (s, 3H,
OMe), 3.33 (m, 1H, H6a), 3.24e3.23 (m, 2H, H5, H6b), 2.74
(s, 1H, OH), 2.30 (t, 2H, JH11eH10¼7.5 Hz, H11), 1.59 (m,
2H, H10), 1.45e1.17 (m, 5H, H8, H9, OH). 13C NMR
(100 MHz, CDCl3) d: 173.8 (CO COOMe), 165.5 (CO Bz),
165.5 (CO Bz), 165.3 (CO Bz), 133.2e128.1 (18C, C Ar),
4.1.18. 5-Methoxycarbonylpentyl 2-O-(2,3,4-tri-O-benzoyl-
b-D-xylopyranosyl)-3,4,6-tri-O-benzyl-b-D-
mannopyranoside (23)
To a mixture of 22 (0.400 g, 0.691 mmol), 4 (0.518 g,
˚
0.829 mmol, 1.2 equiv) and 4 A molecular sieves (400 mg)
0
101.4 (C1), 100.1 (C1 ), 77.5 (C2), 75.5 (C5), 72.9 (C3), 71.7
0
0
0
0
(C2 ), 71.3 (C3 ), 69.9 (C4 ), 69.2 (C7), 67.8 (C4), 62.3 (C5 ),
62.0 (C6), 51.3 (OMe), 33.7 (C11), 28.8 (C8), 25.2 (C9), 24.4
(C10). MS DCIþ-HRMS m/z [MþNH4]þ calcd for
C39H48NO15 770.3024, found 770.3021.
in anhydrous dichloromethane (3 mL), was added under argon,
NIS (0.311 g, 1.382 mmol, 2 equiv) and TfOH (0.012 mL,
0.138 mmol, 0.2 equiv). The mixture was allowed to stir for
10 min and was then filtered, extracted with dichloromethane
and washed with saturated NaHCO3 and Na2S2O3 solutions.
The organic layer was dried over MgSO4, filtered and the sol-
vent was evaporated. The residue was purified by column
chromatography on silica gel (cyclohexane/EtOAc 8:2) to
give 604 mg of 23 (84%) as a syrup. Rf: 0.38 (cyclohexane/
4.1.20. 5-Methoxycarbonylpentyl 2-O-(2,3,4-tri-O-benzoyl-
b-D-xylopyranosyl)-3,4-di-O-benzoyl-6-O-tert-butyl-
dimethylsilyl-b-D-mannopyranoside (25)
To a mixture of 24 (1.060 g, 1.409 mmol), DMAP (0.020 g,
0.160 mmol, 0.1 equiv) in anhydrous pyridine (3 mL) was
added under argon TBDMSCl (0.660 g, 4.227 mmol, 3 equiv).
The mixture turned cloudy and was allowed to stir overnight.
Benzoyl chloride (1.00 mL, 8.612 mmol, 6 equiv) was added
and after 2 h the solvent was evaporated. The product was
extracted with dichloromethane, washed with HCl (1 M) and
neutralised with a saturated NaHCO3 solution. The organic
layer was dried over MgSO4, filtered and the solvent was evap-
orated. The residue was purified by column chromatography
on silica gel (cyclohexane/EtOAc 8:2) to give 1.072 g of 25
(70%) as a white solid. Rf: 0.38 (cyclohexane/EtOAc 8:2).
1
EtOAc 8:2). [a]2D5 ꢁ16 (c 1.0, CHCl3). H NMR (400 MHz,
0
0
0
CDCl3) d: 8.16e7.29 (m, 30H, H Ar), 5.78 (t, 1H, JH3 eH2
¼
¼
0
0
0
0
6.1 Hz, JH3 eH4 ¼6.0 Hz, H3 ), 5.66 (dd, 1H, JH2 eH3
0
0
0
0
6.1 Hz, JH1 eH2 ¼4.2 Hz, H2 ), 5.48 (d, 1H, H1 ), 5.37 (dt,
0
0
0
1H, JH4 eH5b ¼9.0 Hz, H4 ), 4.99 (d, 1H, Jgem¼11.2 Hz,
CHPh), 4.94 (d, 1H, Jgem¼12.0 Hz, CHPh), 4.81 (dd, 1H,
0
0
Jgem¼8.9 Hz, JH5a eH4¼3.5 Hz, H5a ), 4.72 (d, 1H, Jgem
¼
12.0 Hz, CHPh), 4.53 (d, 1H, Jgem¼11.2 Hz, CHPh), 4.50 (d,
1H, Jgem¼12.9 Hz, CHPh), 4.42e4.37 (m, 3H, H1, H2,
1
Mp: 58 ꢀC. [a]D25 ꢁ109 (c 1.0, CHCl3). H NMR (400 MHz,
CDCl3) d: 8.28e7.31 (m, 25H, H Ar), 5.76 (t, 1H, JH4eH3
¼
¼
0
CHPh), 3.88e3.81 (m, 2H, H7a, H5b ), 3.76e3.71 (m, 2H,
0
0
0
0
JH4eH5¼10.0 Hz, H4), 5.70 (t, 1H, JH3 eH2 ¼4.3 Hz, JH3 eH4
H4 H6a), 3.72 (s, 3H, OMe), 3.64 (dd, 1H, JH3eH4¼10.0 Hz,
JH3eH2¼3.0 Hz, H3), 3.49e3.37 (m, 3H, H7b, H6b, H5), 2.28
(t, 2H, JH11eH10¼7.0 Hz, H11), 1.68e1.52 (m, 4H, H10, H8),
1.42e1.35 (m, 2H, H9). 13C NMR (100 MHz, CDCl3) d:
173.9 (CO COOMe), 165.4 (CO Bz), 165.0 (CO Bz), 164.7
0
0
0
0
0
4.6 Hz, H3 ), 5.10 (dd, 1H, JH2 eH3 ¼4.3 Hz, JH2 eH1 ¼3.0 Hz,
0
H2 ), 5.28 (dd, 1H, JH3eH4¼10.0 Hz, JH3eH2¼3.3 Hz, H3),
0
0
0
0
5.23 (d, 1H, JH1 eH2 ¼3.0 Hz, H1 ), 5.09 (m, 1H, H4 ), 4.69
(s, 1H, H1), 4.55 (d, 1H, JH2eH3¼3.3 Hz, H2), 4.41 (dd, 1H,
0
0
0
Jgem¼12.8 Hz, JH5a eH4 ¼2.9 Hz, H5a ), 3.80 (m, 1H, H7a),
0
(CO Bz), 138.2e127.2 (36C, C Ar), 100.4 (C1), 99.6 (C1 ),
80.6 (C3), 74.0 (CH2Ph), 74.8 (C4), 73.0 (CH2Ph), 69.6 (C2),
3.73e3.69 (m, 2H, H5, H6a), 3.68 (s, 3H, OMe), 3.54 (m,
0
0
2H, H7b, H6b), 3.37 (dd, 1H, Jgem¼12.8 Hz, JH5b eH4
¼
0
0
69.2 (CH2Ph), 69.1 (C6), 68.8 (C2 , C3 ), 68.7 (C7), 68.7
0
3.7 Hz, H5b ), 2.24 (t, 2H, JH11eH10¼7.4 Hz, H11), 1.62e1.52
(m, 4H, H8, H10), 1.52e1.51 (m, 2H, H9), 1.46 (s, 9H,
t-Bu), ꢁ0.068 (s, 3H, CH3 TBS), ꢁ0.071 (s, 3H, CH3 TBS).
13C NMR (100 MHz, CDCl3) d: 174.0 (CO COOMe), 166.0
(CO Bz), 165.3 (CO Bz), 165.3 (CO Bz), 165.0 (CO Bz),
0
0
(C4 ), 60.2 (C5 ), 51.2 (OMe), 33.6 (C11), 29.0 (C8 or C10),
25.5 (C9), 24.5 (C8 or C10). MS DCIþ-HRMS m/z [MþNH4]þ
calcd for C60H66NO15 1040.4432, found 1040.4445.
0
164.5 (CO Bz), 133.5e128.1 (30C, C Ar), 99.9 (C1 ), 99.8
0
(C1), 75.5 (C5), 75.4 (C2), 73.7 (C3), 69.4 (C7), 68.5 (C2 ),
4.1.19. 5-Methoxycarbonylpentyl 2-O-(2,3,4-tri-O-benzoyl-
b-D-xylopyranosyl)-b-D-mannopyranoside (24)
0
68.1 (C4), 67.9 (C3 ), 67.4 (C4 ), 63.3 (C6), 59.1 (C5 ), 51.3
(OMe), 33.7 (C11), 29.0 (C8 or C10), 25.6 (t-Bu), 25.5 (C9),
0
0
Compound 23 (1.560 g, 1.524 mmol) was dissolved in
a mixture of EtOAc/methanol (1:1, 30 mL). Pd/C (10%)

M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1533
24.4 (C8 or C10), 18.1 (Cq t-Bu), ꢁ5.4 (CH3 TBS), ꢁ5.5
(CH3 TBS). MS DCIþ-HRMS m/z [MþNH4]þ calcd for
C59H70NO17Si 1092.4413, found 1092.4401.
H9). MS DCIþ-HRMS m/z [MþNH4]þ calcd for C53H56NO17
978.3548, found 978.3563.
4.1.23. 5-Ethoxycarbonylpentyl 2-O-acetyl-3,4,6-tri-
O-benzyl-b-D-glucopyranoside (28)
To a mixture of 12 (0.932 g, 1.420 mmol), ethyl 6-hydroxy-
4.1.21. 5-Methoxycarbonylpentyl 2-O-(2,3,4-tri-
O-benzoyl-b-D-xylopyranosyl)-3,4-di-O-benzoyl-
b-D-mannopyranoside (26)
˚
hexanoate (280 mL, 1.710 mmol, 1.2 equiv) and powdered 4 A
molecular sieves (1 g) in anhydrous dichloromethane (14 mL)
were added under argon, NIS (0.641 g, 2.840 mmol, 2 equiv)
and TfOH (0.025 mL, 0.142 mmol, 0.1 equiv). The mixture
was allowed to stir for 15 min and was then filtered, extracted
with dichloromethane and washed with saturated Na2S2O3 and
NaHCO3 solutions. The organic layer was dried over MgSO4,
filtered and the solvent was evaporated. The residue was puri-
fied by column chromatography on silica gel (cyclohexane/
EtOAc 8:2) to give 620 mg of 28 (69%) as a syrup. Rf: 0.44
Compound 25 (0.550 g, 0.510 mmol) was dissolved in
acetonitrile (3 mL) in a Teflon flask. HF (40% aq, 0.44 mL,
8.850 mmol, 17 equiv) was added and the mixture was al-
lowed to stir overnight. The mixture was diluted with dichloro-
methane and washed with a saturated NaHCO3 solution. The
organic layer was dried over MgSO4, filtered and the solvent
was evaporated. The residue was purified by column chroma-
tography on silica gel (cyclohexane/EtOAc 6:4) to give
0.461 g of 26 (94%) as a white solid. Rf: 0.35 (cyclohexane/
EtOAc 6:4). Mp: 79 ꢀC. [a]D25 ꢁ160 (c 1.0, CHCl3). 1H
NMR (400 MHz, CDCl3) d: 8.18e7.34 (m, 25H, H Ar), 5.91
1
(cyclohexane/EtOAc 8:2). [a]2D5 þ2 (c 1.0, CHCl3). H NMR
(400 MHz, CDCl3) d: 7.43e7.25 (m, 15H, H Ar), 5.09 (t,
1H, JH2eH1¼JH2eH3¼8.0 Hz, H2), 4.88 (d, 1H, Jgem¼11.0 Hz,
CHPh), 4.86 (d, 1H, Jgem¼11.0 Hz, CHPh), 4.76 (d, 1H,
Jgem¼11.0 Hz, CHPh), 4.68 (d, 1H, Jgem¼12.0 Hz, CHPh),
0
0
(t, 1H, JH4eH3¼JH4eH5¼9.9 Hz, H4), 5.76 (t, 1H, JH3 eH2
¼
0
0
0
0
0
JH3 eH4 ¼6.1 Hz, H3 ), 5.82 (dd, 1H, JH2 eH3 ¼6.1 Hz,
0
0
0
JH2 eH1 ¼4.3 Hz, H2 ), 5.32 (dd, 1H, JH3eH2¼3.1 Hz, H3),
4.63 (d, 1H, Jgem¼11.0 Hz, CHPh), 4.62 (d, 1H, Jgem
¼
0
5.21e5.16 (m, 2H, H1 , H4 ), 4.69 (s, 1H, H1), 4.54 (d, 1H,
0
12.0 Hz, CHPh), 4.43 (d, 1H, JH1eH2¼8.0 Hz, H1), 4.17 (q,
2H, J¼7.0 Hz, CH2 OEt), 3.95 (m, 1H, H7a), 3.84e3.72 (m,
4H, H4 H6a, H6b, H3), 3.56 (m, 1H, H5), 3.52 (m, 1H, H7b),
2.34 (t, 2H, JH11eH10¼7.0 Hz, H11), 2.03 (s, 3H, CH3 OAc),
1.74e1.61 (m, 4H, H10, H8), 1.47e1.39 (m, 2H, H9), 1.30
(t, 3H, J¼7.0 Hz, CH3 OEt). 13C NMR (100 MHz, CDCl3)
d: 173.1 (CO COOEt), 169.0 (CO OAc), 137.9e127.2 (18C,
C Ar), 100.6 (C1), 82.6 (C3), 77.7 (C4), 74.8 (C5), 74.6 (2C,
CH2Ph), 73.1 (CH2Ph), 72.0 (C2), 68.9 (C7), 68.8 (C6), 59.8
(CH2 OEt), 33.8 (C11), 28.8 (C8), 25.1 (C9), 24.2 (C10), 20.5
(CH3 OAc), 13.9 (CH3 OEt). MS FABþ-HRMS m/z
[MþK]þ calcd for C37H46O9K 673.2779, found 673.2773.
0
0
JH2eH3¼3.1 Hz, H2), 4.33 (dd, 1H, Jgem¼12.6 Hz, JH5a eH4
¼
0
3.5 Hz, H5a ), 3.77e3.70 (m, 2H, H5, H6a), 3.68 (s, 3H, OMe),
3.67e3.61 (m, 1H, H7a), 3.58e3.54 (m, 1H, H6b), 3.40e3.35
0
(m, 2H, H5b , H7b), 2.55 (s, 1H, OH C6), 2.26 (t, 2H, JH11eH10
¼
7.5 Hz, H11), 1.61e1.53 (m, 2H, H10), 1.49e1.41 (m, 2H, H8),
1.33e1.21 (m, 2H, H9). 13C NMR (100 MHz, CDCl3) d: 173.9
(CO COOMe), 166.0 (CO Bz), 165.2 (CO Bz), 165.2 (CO Bz),
165.2 (CO Bz), 164.8 (CO Bz), 133.3e128.1 (30C, C Ar),
0
100.5 (C1 ), 100.0 (C1), 75.2 (C2), 74.5 (C5), 73.3 (C3), 69.6
0
(C2 ), 69.5 (C7), 68.1 (C4), 68.9 (C3 ), 68.7 (C4 ), 66.4 (C4),
61.6 (C6), 60.1 (C5 ), 51.3 (OMe), 33.6 (C11), 28.8 (C8),
25.3 (C9), 24.3 (C10). MS DCIþ-HRMS m/z [MþNH4]þ calcd
0
0
0
for C53H56NO17 978.3548, found 978.3563.
4.1.24. 5-Ethoxycarbonylpentyl 3,4,6-tri-O-acetyl-2-deoxy-
2-phthalimido-b-D-glucopyranoside (29)
To a mixture of compound 6 (8.350 g, 13.98 mmol), ethyl
4.1.22. 5-Methoxycarbonylpentyl 2-O-(2,3,4-tri-
O-benzoyl-b-D-xylopyranosyl)-3,6-di-O-benzoyl-
b-D-mannopyranoside (27)
6-hydroxy-hexanoate (3.40 mL, 20.98 mmol, 1.5 equiv) and
˚
4 A molecular sieves (4 g) in anhydrous dichloromethane
Compound 25 (1.250 g, 1.162 mmol) was dissolved in an-
hydrous THF (6 mL) under argon. A solution of TBAF (1 M
in THF, 3.5 mL, 3.500 mmol, 3 equiv) was added and the mix-
ture was stirred for 2 h. The solvent was evaporated and the
residue was purified by column chromatography on silica gel
(cyclohexane/EtOAc 7:3) to give 0.836 g of 27 (72%) as
(100 mL) were added under argon, NBS (6.221 g,
34.95 mmol, 2.5 equiv) and TfOH (0.620 mL, 6.99 mmol,
0.5 equiv). After 10 min the mixture was filtered, extracted
with dichloromethane and washed with saturated Na2S2O3
and NaHCO3 solutions. The organic layer was dried over
MgSO4, filtered and the solvent was evaporated. The residue
was purified by column chromatography on silica gel (cyclo-
hexane/EtOAc 5:5) to give 8.06 g of 29 (100%) as a syrup.
Rf: 0.48 (cyclohexane/EtOAc 5:5). [a]2D5 þ18 (c 3.0, CHCl3).
1H NMR (400 MHz, CDCl3) d: 7.78e7.66 (m, 4H, H Phth),
5.69 (dd, 1H, JH3eH2¼10.7 Hz, JH3eH4¼9.3 Hz, H3), 5.27
(d, 1H, JH1eH2¼8.5 Hz, H1), 5.07 (dd, 1H, JH4eH5¼9.8 Hz,
H4), 4.24 (dd, 1H, Jgem¼12.3 Hz, JH6eH5¼4.6 Hz, H6), 4.20
1
a white solid. Rf: 0.27 (cyclohexane/EtOAc 7:3). H NMR
(400 MHz, CDCl3) d: 8.28e7.31 (m, 25H, H Ar), 5.72 (t, 1H,
0
0
0
0
0
0
0
JH3 eH2 ¼6.6 Hz, JH3 eH4 ¼6.4 Hz, H3 ), 5.46 (dd, 1H, JH2 eH3
¼
0
0
0
0
0
6.6 Hz, JH2 eH1 ¼4.8 Hz, H2 ), 5.30 (d, 1H, JH1 eH2 ¼4.8 Hz,
0
0
0
0
0
H1 ), 5.16 (ddd, 1H, JH4 eH3 ¼6.3 Hz, JH4 eH5 ¼4.0 Hz,
0
0
0
JH4 eH5 ¼10.3 Hz, H4 ), 5.10 (dd, 1H, JH3eH4¼10.0 Hz,
JH3eH2¼3.0 Hz, H3), 4.64 (s, 1H, H1), 4.54e4.48 (m, 3H, H2,
0
H6a, H6b), 4.23e4.16 (m, 2H, H5a , H4), 3.74e3.65 (m, 1H,
0
0
(dd, 1H, H2), 4.07 (dd, 1H, JH6 eH5¼2.2 Hz, H6 ), 3.95 (q,
H7a), 3.65 (s, 3H, OMe), 3.66e3.60 (m, 1H, H5), 3.51e3.47
0
2H, J¼7.2 Hz, CH2 OEt), 3.79 (ddd, 1H, H5), 3.73 (dt, 1H,
0
0
(m, 1H, H5b ), 3.43e3.34 (m, 1H, H7b), 2.26 (t, 2H, JH10eH11
7.5 Hz, H11), 1.62e1.49 (m, 4H, H8, H10), 1.38e1.24 (m, 2H,
¼
JH7eH7 ¼9.3 Hz, JH7eH8¼6.2 Hz, H7), 3.36 (dt, 1H, JH7 eH8
¼
0
6.3 Hz, H7 ), 2.00 (s, 3H, CH3 OAc), 1.93 (s, 3H, CH3 OAc),

1534
M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1.88 (m, 2H, H11), 1.76 (s, 3H, CH3 OAc), 1.31 (m, 4H, H8,
H10), 1.11 (t, 3H, CH3 OEt), 1.01 (m, 2H, H9). 13C NMR
(100 MHz, CDCl3) d: 172.9 (CO COOEt), 170.2 (CO OAc),
169.7 (CO OAc), 169.1 (CO OAc), 134.0 (CH Phth), 130.9
(Cq Phth), 123.2 (CH Phth), 97.7 (C1), 71.4 (C5), 70.3 (C3),
69.3 (C7), 68.6 (C4), 61.6 (C6), 59.7 (CH2 OEt), 54.2 (C2),
33.5 (C11), 28.5 (C8 or C10), 24.8 (C9), 23.9 (C8 or C10),
20.3 (CH3 OAc), 20.2 (CH3 OAc), 20.0 (CH3 OAc), 13.8
(CH3 OEt). MS FABþ-HRMS m/z [MþNa]þ calcd for
C28H35NO12Na 600.2057, found 600.2031.
(cyclohexane/EtOAc 8:2) to give 3.48 g of 31 (83%) as a syrup
1
containing 2 anomers (a/b 85:15 estimated by H NMR). Rf:
0.46 (cyclohexane/EtOAc 7:3).
4.1.27. 5-Ethoxycarbonylpentyl 3-O-(2,3,4-tri-O-benzyl-a-
L-fucopyranosyl)-6-O-benzyl-2-deoxy-2-phthalimido-b-D-
glucopyranoside (32)
˚
To a mixture of 31 (0.286 g, 0.299 mmol), 4 A molecular
sieves (400 mg), triethylsilane (0.154 mL, 0.956 mmol,
3.2 equiv) in anhydrous dichloromethane (4 mL) was added
under argon at ꢁ78 ꢀC, TfOH (0.077 mL, 0.867 mmol,
2.9 equiv). After 30 min triethylamine (1 mL) and methanol
(1 mL) were added dropwise. The mixture was allowed to
warm up to room temperature, filtered and concentrated. The
crude product was extracted with dichloromethane and washed
with water. The organic layer was dried over MgSO4, filtered
and the solvent was evaporated. The residue was purified by
column chromatography on silica gel (cyclohexane/EtOAc
7:3) to give 0.228 g of 32 (79%) as a syrup. Rf: 0.34 (cyclohex-
ane/EtOAc 7:3). [a]2D5 þ21 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3) d: 7.90e7.03 (m, 24H, H Ar), 5.41 (d,
1H, JH1eH2¼8.4 Hz, H1), 4.93 (d, 1H, Jgem¼11.4 Hz,
4.1.25. 5-Ethoxycarbonylpentyl 4,6-O-benzylidene-2-deoxy-
2-phthalimido-b-D-glucopyranoside (30)
Compound 29 (5.570 g, 9.65 mmol) was dissolved in anhy-
drous ethanol (20 mL) and anhydrous THF (20 mL) under ar-
gon. Sodium (0.044 g, 1.93 mmol, 0.2 equiv) was added. After
15 min the mixture was neutralised (IR 120Hþ), filtered and
the solvent was evaporated to give a white foam. [Rf: 0.44 (di-
chloromethane/methanol 9:1)]. The crude product was dis-
solved in anhydrous acetonitrile (80 mL) under argon. To the
solution were added successively, benzaldehyde dimethyl ace-
tal (2.90 mL, 19.30 mmol, 2 equiv) and camphorsulphonic
acid (0.671 g, 2.890 mmol, 0.3 equiv). After 1 h a saturated
NaHCO3 solution was added and the product was extracted
with dichloromethane. The organic layer was dried over
MgSO4, filtered and the solvent was evaporated. The residue
was purified by column chromatography on silica gel (cyclo-
hexane/EtOAc 7:3) to give 3.83 g of 30 (73% over two steps)
as a white foam. Rf: 0.19 (cyclohexane/EtOAc 7:3). [a]2D5 ꢁ30
(c 1.5, CHCl3). 1H NMR (400 MHz, CDCl3) d: 7.76e7.26 (m,
0
CHPh), 4.75e4.67 (m, 4H, 3CHPh, H1 ), 4.62 (d, 1H,
Jgem¼11.9 Hz, CHPh), 4.60 (d, 1H, Jgem¼11.4 Hz, CHPh),
4.35 (dd, 1H, JH2eH3¼10.8 Hz, H2), 4.32 (s, 1H, OH), 4.25
(dd, 1H, JH3eH4¼8.1 Hz, H3), 4.20 (d, 1H, Jgem¼13.0 Hz,
0
CHPh), 4.16e4.10 (m, 3H, H5 , CH2 OEt), 3.96 (m, 2H, H6,
0
H7), 3.84 (m, 3H, H2 , H3 , H6), 3.74 (m, 1H, H5), 3.65e
0
0
0
3.58 (m, 3H, H4, H4 , H7 ), 3.53 (d, 1H, Jgem¼13.0 Hz,
CHPh), 2.11 (m, 2H, H11), 1.56 (m, 4H, H8, H10), 1.27 (m,
9H, H Ar), 5.50 (s, 1H, H benzylidene), 5.15 (d, 1H, JH1eH2
¼
0
0
0
5H, CH3 OEt, H9), 1.14 (d, 3H, JH6 eH5 ¼6.5 Hz, H6 ). The re-
gioselectivity was demonstrated by addition of trichloroacetyl
isocyanate and 1H NMR analysis: H4 deshielding d: 5.08
(t, J¼9.3 Hz). 13C NMR (100 MHz, CDCl3) d: 173.2 (CO
COOEt), 168.6 (CO Phth), 167.8 (CO Phth), 138.5, 138.2,
138.0, 137.9 (Cq Bn), 133.4, 132.2, 131.6 (CH Phth),
8.5 Hz, H1), 4.52 (t, 1H, JH3eH2¼JH3eH4¼8.4 Hz, H3), 4.30
(dd, 1H, Jgem¼10.1 Hz, JH6eH5¼3.6 Hz, H6), 4.14 (dd, 1H,
H2), 3.98 (q, 2H, J¼7.2 Hz, CH2 OEt), 3.73 (m, 3H, OH,
0
0
H7, H6 ), 3.52 (m, 2H, H4, H5), 3.35 (dt, 1H, JH7 eH7
¼
0
0
9.8 Hz, JH7 eH8¼6.3 Hz, H7 ), 1.88 (m, 2H, H11), 1.31 (m,
4H, H8, H10), 1.14 (t, 3H, CH3 OEt), 1.02 (m, 2H, H9). 13C
NMR (100 MHz, CDCl3) d: 173.1 (CO COOEt), 136.8,
133.7, 131.1, 128.7, 127.8, 125.9 (C Ar), 101.2 (C benzyli-
dene), 98.4 (C1), 81.7 (C4), 69.2 (C7), 68.2 (C6), 67.9 (C3),
65.8 (C5), 59.7 (CH2 OEt), 56.6 (C2), 33.5 (C11), 28.5 (C8
or C10), 24.8 (C9), 23.9 (C8 or C10), 13.8 (CH3 OEt). MS
FABþ-HRMS m/z [MþNa]þ calcd for C29H33NO9Na
562.2053, found 562.2048.
0
128.2e122.6 (C Ar), 100.5 (C1 ), 98.0 (C1), 83.0 (C3), 78.5
0
0
0
(C3 ), 77.6 (C4 ), 75.0 (C5), 74.5 (CH2Ph), 73.7 (C2 ), 73.2
(CH2Ph), 73.1 (CH2Ph), 72.1 (CH2Ph), 71.0 (C4), 69.1 (C6,
0
C7), 68.2 (C5 ), 59.8 (CH2 OEt), 54.4 (C2), 33.8 (C11), 28.8
0
(C8 or C10), 25.1 (C9), 24.1 (C8 or C10), 16.2 (C6 ), 14.0
(CH3 OEt). MS FABþ-HRMS m/z [MþNa]þ calcd for
C56H63NO13Na 980.4197, found 980.4183.
References and notes
4.1.26. 5-Ethoxycarbonylpentyl 3-O-(2,3,4-tri-O-benzyl-a-
L-fucopyranosyl)-4,6-O-benzylidene-2-deoxy-2-
phthalimido-b-D-glucopyranoside (31)
To a mixture of 30 (2.340 g, 4.336 mmol), 7 (3.100 g,
˚
5.203 mmol, 1.2 equiv) and 4 A molecular sieves (2 g) in an-
1. Mallet, J.-M.; Sinay, P. Classics in Total Synthesis Oligosaccharides
¨
and Glycoconjugates. In Carbohydrates in Chemistry and Biology;
Ernst, B., Hart, G. W., Sinay, P., Eds.; Wiley-VCH: Weinheim, 2000;
¨
pp 467e492.
hydrous dichloromethane (15 mL), were added under argon,
NIS (1.951 g, 8.672 mmol, 2 equiv) and TfOH (0.038 mL,
0.433 mmol, 0.1 equiv). After 20 min the mixture was filtered,
extracted with dichloromethane and washed with saturated
NaHCO3 and Na2S2O3 solutions. The organic layer was dried
over MgSO4, filtered and the solvent was evaporated. The res-
idue was purified by column chromatography on silica gel
2. (a) Garegg, P. J. Adv. Carbohydr. Chem. Biochem. 1997, 52, 179e205; (b)
Amatore, C.; Jutand, A.; Mallet, J.-M.; Meyer, G.; Sinay, P. J. Chem. Soc.,
¨
Chem. Commun. 1990, 718e719; (c) Marra, A.; Mallet, J.-M.; Amatore,
C.; Sinay, P. Synlett 1990, 572e574; (d) Zhang, Y.; Mallet, J.-M.; Sinay,
¨
¨
P. Carbohydr. Res. 1992, 236, 73e88; Ferrier, R. J.; Hay, R. W.;
Vethaviyasar, N. Carbohydr. Res. 1973, 27, 55e61.
3. Dohi, H.; Nishida, Y.; Takeda, T.; Kobayashi, K. Carbohydr. Res. 2002,
337, 983e989.

M. Collot et al. / Tetrahedron 64 (2008) 1523e1535
1535
4. (a) Kajimoto, T.; Ishioka, Y.; Katoh, T.; Node, M. Bioorg. Med. Chem.
Lett. 2006, 16, 5736e5739; (b) Hasegawa, J. Y.; Hamada, M.; Miyamoto,
T.; Nishide, K.; Kajimoto, T.; Uenishi, J.; Node, M. Carbohydr. Res. 2005,
340, 2360e2368.
12. For reviews: (a) Fotish, K.; Vieth, S. Glycoconjugate J. 2001, 18, 373e
´
¨
390; (b) Paschinger, K.; Fabini, G.; Schuster, D.; Rendic, D.; Wilson,
I. B. H. Acta Biolchim. Pol. 2005, 52, 629e632.
13. (a) van der Veen, M. J.; van Ree, R.; Aalberse, R. C.; Akkerdaas, J.;
Koppelman, S. J.; Jansen, H. M.; van der Zee, J. S. J. Allergy Clin. Immu-
nol. 1997, 100, 327e334; (b) Foetisch, K.; Westphal, S.; Lauer, I.; Retzek,
M.; Altmann, F.; Kolarich, D.; Scheurer, S.; Vieths, S. J. Allergy Clin.
Immunol. 2003, 111, 889e896.
14. Ballmer-Weber, B. K.; Wangorsch, A.; Bohle, B.; Kaul, S.; Kundig,
T.; Fotisch, K.; van Ree, R.; Vieths, S. Clin. Exp. Allergy 2005, 35,
970e978.
5. Jing, Y. Q.; Huang, X. F. Tetrahedron Lett. 2004, 45, 4615e4618.
6. Recent references for the use of odourless thiols in organic chemistry: (a)
Yu, H. F.; Dong, D. W.; Yan, O. Y.; Wang, Y.; Liu, Q.; Yu, H. F.; Dong,
D. Synlett 2007, 151e155; (b) Matoba, M.; Kajimoto, T.; Nishide, K.;
Node, M. Chem. Pharm. Bull. 2006, 54, 141e146; (c) Dong, D. W.; Yu,
H. F.; Yan, O. Y.; Liu, Q.; Bi, X. H.; Lu, Y. M. Synlett 2006, 283e287;
(d) Yu, H. F.; Dong, D. W.; Yan, O. Y.; Liu, Q.; Wang, Y. Lett. Org.
Chem. 2005, 2, 755e759; (e) Yoshikai, K.; Hayama, T.; Nishimura, K.;
Yamada, K.; Tomioka, K. J. Org. Chem. 2005, 70, 681e683; (f) Yu,
H. F.; Liu, Q.; Yin, Y. B.; Fang, Q. X.; Zhang, J. P.; Dong, D. W. Synlett
2004, 999e1002; (g) Miyazaki, T.; Han-ya, Y.; Tokuyama, H.; Fukuyama,
T. Synlett 2004, 477e480; (h) Nishide, K.; Node, M. J. Synth. Org.
Chem. Jpn. 2004, 62, 895e910; (i) Nishide, K.; Patra, P. K.; Matoba, M.;
Shanmugasundaram, K.; Node, M. Green Chem. 2004, 6, 142e146; (j)
Nishide, K.; Ohsugi, S.; Shiraki, H.; Tamakita, H.; Node, M. Org. Lett.
2001, 3, 3121e3124.
15. van Ree, R.; Cabanes-Macheteau, M.; Akkerdaas, J.; Milazzo, J.-P.;
Loutelier-Bourhis, C.; Rayon, C.; Villalba, M.; Koppelman, S.; Aalberse,
R.; Rodriguez, R.; Faye, L.; Lerouge, P. J. Biol. Chem. 2000, 275, 11451e
11458.
16. Synthetic oligomannosides, preparation and uses thereof, WO/2001/
038338, 2001. Chevalier, R.; Esnault, J.; Vandewalle, P.; Sendid, B.;
Colombel, J.-F.; Poulain, D.; Mallet, J.-M. Tetrahedron 2005, 61,
7669e7677.
17. (a) Chevalier, R.; Colsch, B.; Afonso, C.; Baumann, N.; Tabet, J.-C.; Mallet,
J.-M. Tetrahedron 2006, 62, 563e577; (b) Gourier, C.; Pincet, F.; Perez, E.;
7. Magano, J.; Chen, M. H.; Clark, J. D.; Nussbaumer, T. J. Org. Chem.
2006, 71, 7103e7105.
Zhang, Y.; Mallet, J.-M.; Sinay, P. Glycoconjugate J. 2004, 165e174.
¨
8. Kumar, R. K.; Cole, D. L.; Ravikumar, V. T. Nucleosides Nucleotides
Nucleic Acids 2003, 453e460.
9. Li, Z.; Gildersleeve, J. C. J. Am. Chem. Soc. 2006, 128, 11612e11619.
18. Franks, N. E.; Montgomery, R. Carbohydr. Res. 1968, 6, 286e298.
19. Ferrier, R. J.; Furneaux, R. H. Carbohydr. Res. 1976, 52, 63e68.
20. Lichtenthaler, F. W.; Lindler, H. J. Carbohydr. Res. 1990, 200, 91e99.
21. D’accorso, I.; Schueller, I. M. Carbohydr. Res. 1988, 124, 177e184.
22. Hirano, S. Carbohydr. Res. 1971, 16, 229e231.
´
´
´
´
10. (a) van der Ven, J. G. M.; Kerekgyarto, J.; Kamerling, J. P.; Liptak, A.;
´
Vliegenthart, J. F. G. Carbohydr. Res. 1994, 264, 45e62; (b) Kerekgyarto,
J.; van der Ven, J. G. M.; Kamerling, J. P.; Liptak, A.; Vliegenthart,
´ ´
´
23. Flowers, H. M.; Levy, A.; Sharon, N. Carbohydr. Res. 1967, 4, 189e195.
´
´ ´
J. F. G. Carbohydr. Res. 1993, 238, 135e145; (c) Kerekgyarto, J.;
24. Jouault, T.; Mallet, A.; Mallet, J.-M.; Camus, D.; Sinay, P.; Poulain, D.
¨
J. Leukocyte Biol. 1996, 60, 81e87.
´
Kamerling, J. P.; Bouwstra, J. B.; Vliegenthart, J. F. G.; Liptak, A. Carbo-
hydr. Res. 1989, 186, 51e62.
11. Petersen, A.; Vieths, S.; Aulepp, H.; Schlaak, M.; Becker, W.-M. J Allergy
Clin. Immunol. 1996, 98, 805e815.
25. Sakagami, M.; Hamana, H. Tetrahedron Lett. 2000, 41, 5547e5551.
26. Chambers, D. J.; Evans, G. R.; Fairbanks, A. J. Tetrahedron 2004, 60,
8411e8419.