Indium-promoted Barbier-type allylations in aqueous media: A convenient approach to 4-C-branched monosaccharides and (1→4)-C-disaccharides

Article abstract of DOI:10.1016/j.carres.2004.09.010

Starting from methyl 6-bromo-4,6-dideoxy-α-d-threo-4-enopyranoside, 4-C-branched sugars have been prepared through indium-promoted Barbier-type allylation of various aldehydes in aqueous media followed by hydroboration of the resulting double bond. The intermediate unsaturated monosaccharides were shown to rearrange in acidic media to give 4-C-acetyl-5-C-alkyl pyranose compounds. From β-1-formyl sugars the corresponding β-(1→4)-C- disaccharides were obtained.

Full text of DOI:10.1016/j.carres.2004.09.010

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 2737–2747
Indium-promoted Barbier-type allylations in aqueous media:
a convenient approach to 4-C-branched monosaccharides
and (1!4)-C-disaccharides
´ ´
Eric Levoirier, Yves Canac, Stephanie Norsikian and Andre Lubineau
*
´
´
Laboratoire de Chimie Organique Multifonctionnelle, associe au CNRS (UMR 8614), Institut de Chimie Moleculaire et des
´
´ ˆ
Materiaux d’Orsay (ICMMO), Universite Paris-Sud, Bat. 420, F-91405 Orsay, France
Received 8 July 2004; accepted 22 September 2004
Abstract—Starting from methyl 6-bromo-4,6-dideoxy-a-D-threo-4-enopyranoside, 4-C-branched sugars have been prepared through
indium-promoted Barbier-type allylation of various aldehydes in aqueous media followed by hydroboration of the resulting double
bond. The intermediate unsaturated monosaccharides were shown to rearrange in acidic media to give 4-C-acetyl-5-C-alkyl pyra-
nose compounds. From b-1-formyl sugars the corresponding b-(1!4)-C-disaccharides were obtained.
Ó 2004 Elsevier Ltd. All rights reserved.
Keywords: Organic synthesis in water; Indium-mediated allylations; C-branched sugars; C-disaccharides
1. Introduction
ogy to 6-bromo-4-enopyranoside, which allows access to
various 4-C-branched monosaccharides and (1!4)-C-
disaccharides.
The stereospecific formation of carbon–carbon bonds is
currently the subject of intense research. In carbohy-
drate chemistry, the regio- and stereoselective synthesis
of branched sugars has mainly been stimulated by their
occurrence in a large variety of natural products.1 More-
over, relatively few methods of general preparative
significance are available for the synthesis of such
compounds.2
Recently, we reported a very convenient protocol for
the preparation of C-branched monosaccharides and
C-disaccharides under indium promoted Barbier-type
allylations in aqueous media.3 Indeed because indium-
mediated reactions can be carried out in such media,
they were shown to be particularly suited for carbohy-
drates and their analogues.4
2. Results and discussion
The synthesis of the key compound for the allylation
reaction, 6-bromo-4,6-dideoxy-a-D-threo-4-enopyrano-
side 7 is summarized in Scheme 1. We started from
commercial methyl a-D-glucopyranoside 1. After
quantitative acetylation under standard conditions (ace-
tic anhydride in pyridine, overnight), the peracetylated
derivative 2 was treated with lipase from Candida cylin-
dracea in a mixture of phosphate buffer (0.1M; pH7.0)
and di-n-butyl ether, to give methyl 2,3,4-tri-O-acetyl-
a-D-glucopyranoside 3 in 97% yield.5 In the latter reac-
tion, we observed, as reported, complete and regioselec-
tive hydrolysis of the primary acetyl ester. Then, PCC
oxidation6 gave directly the unsaturated aldehyde 47 in
78% yield provided that the reaction was performed
on a small scale. On a larger scale, we preferred the
Swern oxidation (dimethyl sulfoxide/oxalyl chloride/tri-
ethylamine), which gave 4 in 91% reproducible yield.8
In order to extend our preliminary approach, which
started from 2-bromo-3-enopyranoside and 4-bromo-2-
enopyranoside derivatives, we now apply this methodol-
*
Corresponding author. Tel.: +33 169154719; fax: +33 169154715;
e-mail: lubin@icmo.u-psud.fr
0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.09.010

2738
E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
OH
OH
OAc
CHO
O
O
O
O
c
b
a
AcO
AcO
HO
AcO
AcO
AcO
HO
OAc
OAc
OH
OAc
4
OMe
OMe
OMe
OMe
3
2
1
d
OH
Br
Br
O
O
O
f
e
AcO
AcO
HO
OAc
OAc
OH
OMe
OMe
OMe
6
5
7
Scheme 1. Reagents and conditions: (a) Ac2O, pyridine (quantitative yield); (b) lipase from C. cylindracea, phosphate buffer (0.1M, pH7.0)/Bu2O
(97%); (c) Me2SO, (CO)2Cl2, Et3N, CH2Cl2 (91%); (d) NaBH4, MeOH (91%); (e) CBr4, (C6H5)3P, CH2Cl2 (93%); (f) LiOH, MeOH/water (97%,
overall yield 72%).
Then, the unsaturated aldehyde 4 was reduced with
NaBH4 in MeOH to provide the allyl alcohol 5 in 91%
yield. Finally, under standard bromination conditions
(triphenylphosphine, carbon tetrabromide) followed by
deacetylation with lithium hydroxide in a 3:1 mixture
of MeOH–water (97%), we obtained the desired
6-bromo-4-enopyranoside 7 (72% overall yield for the
six steps from 1).
obtained along with compound 8, a small amount
(9%) of 26, which resulted from the reduction in water
of the starting bromide with indium. Indeed, when 7
was treated with indium(0), alone without any aldehyde
in a 1:1 THF–phosphate buffer (0.05M; pH7.0)/THF
mixture, we obtained in 1h 26 in 73% yield. The 13C
NMR spectrum of 26 shows clearly an exocyclic double
bond at C-5 (97.2 and 153.1ppm) and a methylene
group at C-4 (36.2ppm). It is noteworthy that this
reduction, which occurred to a small extent in the case
of the primary bromide 7, did not occur at all when
using a secondary bromide.3
If the reaction is conducted in pure water, in the ab-
sence of the phosphate buffer, the 4-C-adduct 8 is slowly
transformed (30% after 1.5h) into two new products
9a,b as a 1:3 mixture of the two a and b anomers. These
compounds 9a,b were fully characterized by spectral
analysis. For both compounds, 1H and 13C NMR
spectroscopy indicates the presence of the 5-C-phenyl
moiety in equatorial orientation instead of the H-6
and H-60 protons and a 4-C-acetyl group in axial orien-
tation. Acetylation of 9a,b led to 10a,b whose NMR
data confirmed the structure. Indeed, we observed a
Then we tested the allylation reactions with various
aldehydes under indium-promoted Barbier-type condi-
tions. All the results are summarized in Table 1.
First, we tried the reaction with benzaldehyde. It took
place in a mixture of 2:1 THF–phosphate buffer (0.11M;
pH7.0) at rt for 1.5h to give the adduct 8 in 86% yield as
a unique stereoisomer resulting from complete regio-
and diastereoselectivity (Table 1, entry 1). The structure
1
of 8 was deduced from NMR analysis. The H NMR
spectrum notably exhibits a doublet of doublet (J3,4
8.5Hz and J4,7 4.0Hz) for H-4, indicating equatorial
alkylation at C-4. In 13C NMR spectroscopy, the pres-
ence of a quaternary carbon atom and a secondary car-
bon atom in the olefinic shift area are in good agreement
with an exocyclic double bond in C-5,6 position. We
Table 1. Reactions of 7 with various aldehydes
Br
HO
R
O
O
conditions (a)
+
RCHO
H
HO
HO
OH
OH
OMe
OMe
7
Entry
RCHO
Products
Condb
Yieldc (%)
Eq./ax.d
Dr: S/Rd
1
2
3
4
PhCHO
HCHO
13
8
1.5
3
86
73
57
45
1/0
ꢀ100/0
—
11a,b
14
19a,b
0.66/0.34
1/0
0.64/0.36
1.5
2
ꢀ100/0
ꢀ100/0
18
a RCHO (3equiv), In (2equiv), 2:1 THF–phosphate buffer (0.11M, pH7.0).
b Conditions: reaction time (h); rt.
c Isolated yields.
d Diastereomeric ratio determined within the accuracy of 1H and 13C NMR spectra.

E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
2739
HCl 0.1 M
aq
O
Br
90%
+
C H
6
5
HO
O
O
O
a
H C
5
6
H
HO
HO
RO
OR
OH
OH
OR
R = H 9α,β
OMe
OMe
HO
7
8
b
R = Ac 10α,β
O
HO
H C
5
6
H
OH
H C
5
O
HO
H
6
O
HO
OH
OH
OMe
H
Scheme 2. Reagents and conditions: (a) water, PhCHO (3equiv), In (2equiv); 8, 5%; 9a,b (a/b: 1:3, 30%) or 2:1 THF–phosphate buffer (0.11M,
pH7), PhCHO (3equiv), In (2equiv); 8, 86%; 9a,b, 0%; (b) Ac2O, py.
doublet of doublet for H-3 (J3,4 6Hz), which confirmed
the 4-C-acetyl group in axial orientation and a doublet
for H-5 (J3,5 3.5Hz) indicating the presence of the
phenyl group in equatorial orientation.
over, in this case, two six-membered transition states
seem to be possible, a Ôtrans-decalinÕ state A and a Ôcis-
decalinÕ state B (Chart 1). Generally, trans-decalin is
more stable than its cis-isomer; accordingly, the alkyl-
ation at C-4 in equatorial orientation in 8 is in favor of
the formation of the Ôtrans-decalinÕ state A. Moreover,
the C-7 (S) configuration indicates that the phenyl group
is in the more favorable equatorial orientation in the
transition state as depicted in Chart 1A.
Then in a second step, the reaction was extended to
others aldehydes. In the case of formaldehyde (Table
1, entry 2), we obtained at rt in 3h, a mixture of axial
and equatorial C-4 adducts 11a,b (73% yield in a 2:1
ratio in favor of the equatorial adduct) and the reduced
compound 26 (7%). Compound 11a,b were fully charac-
terized after peracetylation to 12a,b. The presence of the
two epimers at C-4 in 11a,b can be explained by the for-
mation of the two six-membered cyclic transition states
A and B (Chart 1) and certainly reflects the low energy
difference between these two states in the case of formal-
dehyde, resulting from a decrease in the steric hindrance
compared with the reaction with benzaldehyde.
Next, we examined the reaction between 7 and
3-O-benzyl-1,2-O-isopropylidene-a-D-xylo-dialdose 13.9
In this case, the reaction was less efficient than with
benzaldehyde and the C-4 equatorial adduct was
obtained at rt in 1.5h as a single diastereoisomer 14 in
57% yield (Table 1, entry 3) along with the reduced
derivative 26 (18%). Compound 14 was fully character-
ized after peracetylation. Treatment of 14 by aq HCl fol-
lowed by acetylation gave a 11:9 mixture of the two
anomers 17a,b in 81% yield, which confirmed that the
configuration of the new stereogenic center C-7 in the
starting compound 14 was (S). These results indicate
clearly that in this case, as previously with benzalde-
hyde, the bulky substituent (furanose ring) is in the more
favorable equatorial orientation in a Ôtrans-decalinÕ-like
six-membered transition state.
In fact, without buffering the reaction mixture, 9a,b
arise from the acid hydrolysis of the labile enol ether
derivative 8 as shown in Scheme 2. After electrophilic
addition of water followed by opening of the ring with
elimination of the anomeric methoxy group, the cycliza-
tion of the C-7 hydroxyl group onto the aldehyde led to
the keto-derivatives 9a,b. In order to confirm these
results, compound 8 was treated by 0.1M aq HCl. Effec-
tively, in these conditions, 9a,b was obtained in 90%
yield in 5min as a mixture of anomers (a/b, 1:3).
Interestingly, the 4-C-5-C-substituted D-galacto-like
structure of 9a,b confirms the alkylation at C-4 in equa-
torial orientation and the configuration of the second
new stereogenic center at C-7 in 8. Indeed, C-4 in 9a,b
(or 10a,b) arises from C-7 in 8. On the basis of these
results, configuration at C-7 was assigned as (S).
From a mechanistic point of view, our results can be
explained by the formation of the currently accepted
six-membered cyclic transition state between the carbon-
yl compound and the allylindium sugar moiety. More-
O
In
R
O
In
H
H
O
R
O
H
H
H
HO
H
OH
HO
OMe
OH
OMe
"trans-decalin" A
"cis-decalin" B
OBn
OBn
O
OBn
O
O
BnO
BnO
BnO
C H , H,
R =
6
5
,
O
R = H;
BnO
OBn
OBn
CMe
O
2
Finally, to obtain analogues of C-oligosaccharides,
we turned our attention to the reaction between the
Chart 1. Transition states between the carbonyl compound and the
allylindium sugar moiety.

2740
E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
RO
RO
O
O
CHO
O
OBn
RO
RO
OR
OR
O
OMe
OMe
R = H
11a
R = H
11b
CMe
O
2
13
R = Ac 12a
R = Ac 12b
CMe
2
O
O
O
O
O
C H
6
RO
5
O
Me C
2
OBn
O
O
O
H
OBn
BnO
O
O
RO
CHO
RO
BnO
OR
OR
RO
OBn
OMe
R = H 16α,β
R = Ac 17α,β
R = H 14
R = Ac 15
18
BnO
BnO
OBn
O
OBn
O
RO
O
BnO
H
BnO
BnO
H
RO
RO
O
OBn
OR
1
OMe
OBn
R O
R = H 19a
R = Ac 20a
1
R O
19b
1
OMe
R = R = H
1
R = OH
R
= Ac 20b
21b
1
R = R = Ac
OBn
OBn
OBn
OBn
O
OBn
BnO
BnO
O
O
O
O
O
O
RO
HO
RO
OR
OR
OR
OR
OH
OMe
R = H 22α,β
R = Ac 23α,β
R = H 24α,β
R = Ac 25α,β
26
6-bromo-enopyranoside derivative 7 and the b-C-linked
2,3,4,6-tetra-O-benzyl-b-D-glucosyl aldehyde 18.10 The
reaction gave an inseparable 16:9 mixture of the two ad-
ducts 19a,b in 45% yield along with 26 (30%). It is diffi-
cult at this stage to deduce the stereochemistry at C-4
J3,4 6Hz for both anomers still did not allow to assign
the configuration at C-4. However, a NOESY experi-
ment showed clearly a strong NOE effect between H-4
and both H-3 and H-5 but not with H-2, which implied
an equatorial H-4 and an axial methylketone. In 25a,b,
the coupling constants J3,4 8Hz for the a anomer and
10.5Hz for the b anomer indicate an equatorial orient-
ation for the methylketone substituent. This was con-
firmed through NOESY experiments, which showed
strong effects between H-4 and H-2 but not with H-3
and H-5. From these correlations, it can be concluded
that for the major stereoisomer 19a, the alkylation
operated at C-4 in equatorial orientation with C-7 (S)
configuration. As previously, the bulkier substituent
(pyranosidic ring) is in more favorable equatorial orien-
tation with a Ôtrans-decalinÕ transition state. For the
minor isomer 19b, the alkylation operated in C-4 axial
position with C-7 (S) configuration, which implied a
cis-decalin transition state in which the pyranosidic ring
is in axial orientation. This could be explained by a chel-
ation of the indium atom with an oxygen atom in 18
1
from the H NMR spectrum of the 19a,b mixture as
the coupling constants J3,4 (6Hz) were the same for both
compounds. Therefore, the mixture was acetylated (16h,
Ac2O–pyridine) at rt to give the fully acetylated com-
pound 20a and 20b in which the tertiary hydroxyl group
remained unchanged, which allowed the separation at
this stage. Then, 20b was fully acetylated at 40°C for
24h to give 21b. However, it is still difficult to deduce
1
from the H NMR spectrum the stereochemistry at C-
4 in 20a (J3,4 5.5Hz) and 21b (J3,4 6Hz). Compounds
20a and 21b were separately treated with 0.1N aq HCl
to give the rearranged products 22a,b and 24a,b, respec-
tively, which were acetylated to 23a,b and 25a,b in
which the perbenzyl glucosyl moiety was in equatorial
orientation indicating a C-7 (S) configuration for both
20a and 21b. However, in 23a,b the coupling constant

E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
2741
BnO
OBn
O
C H
6
5
OBn
OBn
OMe
BnO
O
O
H
O
H
OBn
OBn
OBn
O
OAc
In
In
O
O
H
BnO
OBn
OAc
a, b,c
OBn
O
21b
O
H
H
AcO
H
H
OAc
HO
HO
OMe
OH
OH
28
OMe
Scheme 4. Reagents and conditions: (a) BH3, THF; (b) H2O2,
phosphate buffer (0.5M, pH7.0); (c) Ac2O, pyridine; 83% overall yield.
Chart 2. Possible transition states with chelation of indium atom in the
reaction with 18.
(either O-30 or endocyclic oxygen), which cannot oper-
ate if the sugar is in equatorial orientation (Chart 2).
We have in fact, already found such chelation in previ-
ous cases.3 This axial orientation of the bulkier substit-
uent in the transition state can be correlated with the
moderate yield (45%) obtained with the b-C-linked
2,3,4,6-tetra-O-benzyl-b-D-glucosyl aldehyde 18 in com-
parison to that of previous aldehydes.
In fact, all these allylation reactions led to unsaturated
analogues of C-branched sugars or C-disaccharides,
which need further elaboration to saccharides by
hydroboration of the exocyclic double bond. As an
example, we focused on the functionalization of 20a
and 21b to disaccharides. Thus, hydroboration of 20a
with diborane–tetrahydrofuran followed by oxidation
with hydrogen peroxide11 in phosphate buffer (0.5M;
pH7.0) and acetylation (Ac2O–pyridine) led to a pro-
tected C-disaccharide derivative [D-Glc-b-(1!4)-C-L-
Ido] 27 as a single diastereoisomer, in 91% overall yield
(Scheme 3).
The stereochemistry of the C-disaccharide 27 resulted
from the attack of the electrophile onto the double bond
on the opposite side of the C-1 and C-4 substituents.
Moreover, steric hindrance of the 2,3,4,6-tetra-O-benz-
yl-b-D-glucosyl moiety could explain the complete dia-
stereoselectivity of this reaction.
In the same way, hydroboration of compound 21b
with diborane–tetrahydrofuran followed by oxidation
with hydrogen peroxide in phosphate buffer (0.5M;
pH7.0) and then acetylation gave the protected C-disac-
charide derivative [D-Glc-b-(1!4)-C-D-Gal] 25 in 83%
yield as a single diastereoisomer (Scheme 4). Here the
formation of 25 could be explained by attack of the
electrophile at C-5 on the opposite side of the 2,3,4,6-
tetra-O-benzyl-b-D-glucosyl moiety located at the axial
C-4 position.
In conclusion, we have reported an efficient synthesis
of 4-C-branched monosaccharides and (1!4)-C-disac-
charides in aqueous media through indium-promoted
Barbier-type allylations. Particularly, we have described
an effective access to protected Glc-b-(1!4)-C-Ido and
Glc-b-(1!4)-C-Gal derivatives from methyl a-D-gluco-
pyranoside. The synthesis of these new compounds
exemplifies the application of this recently developed
method.
3. Experimental
3.1. General methods and materials
All moisture sensitive reactions were performed under
argon using oven-dried glassware. If necessary, solvents
were dried and distilled prior to use. Reactions were
monitored on E. Merck Silica Gel 60 F254 plates. Detec-
tion was performed using UV light, iodine and/or 5%
H2SO4 in EtOH, followed by heating. Flash chromatog-
raphy was performed on Silica Gel 6–35lm. 1H and 13
C
NMR spectra were recorded at rt with Bruker AC 200,
250, or AM 400 spectrometers. Chemical shifts are re-
ported in d relative to Me4Si for 1H and 13C NMR spec-
tra (external reference for D2O) and relative to the
CDCl3 resonance at 77.00ppm for 13C NMR spectra
in CDCl3. Melting points were measured on a Reichert
apparatus and were uncorrected. Optical rotations were
measured on an Electronic Digital Jasco DIP-370 Pola-
rimeter. Mass spectra were recorded in positive mode on
a Finnigan MAT 95 S spectrometer using electrospray
ionization. Elemental analyses were performed at the
Service Central de Microanalyses du CNRS (Gif-sur-
Yvette, France).
OBn
OAc
O
H
O
a, b,c
3.2. Methyl 2,3-di-O-acetyl-4-deoxy-a-D-threo-hex-4-
enopyranoside (5)
OAc
OAc
BnO
BnO
20a
AcO
OBn
OMe
27
Sodium borohydride (0.120g, 3.2mmol) was added to a
cooled (0°C) soln of 4 (0.816g, 3.2mmol) in MeOH
(20mL). The mixture was stirred at 0°C for 10min, then
Scheme 3. Reagents and conditions: (a) BH3, THF; (b) H2O2,
phosphate buffer (0.5M, pH7.0); (c) Ac2O, pyridine; 91% overall yield.

2742
E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
quenched with water, and extracted with CH2Cl2. The
organic phase was dried (MgSO4), then concentrated.
Flash chromatography of the residue (1:1 petroleum
ether–EtOAc) gave 5 (0.750g, 91%) as a colorless oil.
[a]D +277 (c 1.0, CH2Cl2); 1H NMR (250MHz, CDCl3):
d 5.34 (m, 1H, H-3), 5.06 (dd, 1H, J2,1 2.5, J2,3 7Hz, H-
2), 4.98–4.92 (br s, 2H, H-1, H-4), 3.99 (m, 2H, H-6, H-
60), 3.47 (s, 3H, CH3O), 2.07, 2.01 (2s, 6H, acetyl); 13C
NMR (63MHz, CDCl3): d 170.0 (C@O), 169.9, 152.6
(C-5), 97.2, 94.8 (C-1, C-4), 68.9, 66.6 (C-2, C-3), 60.8
(C-6), 56.0 (CH3O), 20.5, 20.3 (acetyl). Anal. Calcd for
C11H16O7: C, 50.77; H, 6.20; O, 43.03. Found: C,
50.48; H, 6.17; O, 43.49.
3.5. Methyl 4-C-[(S)-1-phenyl-1-hydroxymethyl]-4,6-
dideoxy-a-D-xylo-hex-5-enopyranoside (8) and methyl
4,6-deoxy-a-L-threo-hex-5-enopyranoside (26)
Indium powder (115mg, 1mmol) was added to a soln of
7
(120mg, 0.5mmol) and benzaldehyde (153lL,
1.5mmol) in a mixture of THF (1mL) and phosphate
buffer (pH7, 0.11M, 0.5mL). After stirring for 1.5h,
the mixture was neutralized with satd aq NaHCO3.
The suspension was filtered over Celite, washed with
EtOH, and the filtrate was concentrated. Flash chroma-
tography (1:4 petroleum ether–EtOAc) of the residue
gave 8 (0.114g, 86%) as white crystals followed by 26
(7mg, 9%) as a colorless oil.
Compound 8: mp 98°C (Et2O); [a]D +99 (c 1.1,
3.3. Methyl 2,3-di-O-acetyl-6-bromo-4,6-dideoxy-a-D-
threo-hex-4-enopyranoside (6)
1
CH2Cl2); H NMR (250MHz, CDCl3): d 7.52–7.14 (m,
5H, Ar), 5.25 (br s, 1H, H-1), 4.81 (d, 1H, J7,4 4.0Hz,
H-7), 4.68 (s, 1H, H-60), 4.39 (s, 1H, H-6), 4.20 (t, 1H,
J3,2 = J3,4 8.5Hz, H-3), 3.71 (dd, 1H, J2,1 3.5, J2,3
8.5Hz, H-2), 3.44 (s, 3H, CH3O), 2.82 (dd, 1H, J4,7
4.0, J4,3 8.5Hz, H-4); 13C NMR (63MHz, CDCl3): d
152.0 (C-5), 142.2, 128.2, 126.9, 125.9 (Ar), 100.2, 99.7
(C-1, C-6), 72.8, 70.0, 69.1 (C-2, C-3, C-7), 55.7
(CH3O), 51.4 (C-4). Anal. Calcd for C14H18O5: C,
63.15; H, 6.81; O, 30.04. Found: C, 63.21; H, 6.92; O,
30.25.
PPh3 (0.906g, 3.46mmol) and CBr4 (1.05g, 3.17mmol)
were added to a cooled (ꢁ78°C) soln of 5 (0.750g,
2.9mmol) in CH2Cl2 (30mL). The suspension was stir-
red at 0°C for 2h, then quenched with satd aq NaHCO3,
and extracted with CH2Cl2. The organic phase was dried
(MgSO4) then concentrated. Flash chromatography of
the crude residue (1:4 petroleum ether–EtOAc) gave 6
(0.872g, 93%) as white crystals: mp 89°C (Et2O); [a]D
1
+265 (c 1.1, CH2Cl2); H NMR (250MHz, CDCl3): d
29
1
Compound 26: ½aꢂ +84 (c 0.8, MeOH); H NMR
D
5.45 (dd, 1H, J3,4 2.9, J3,2 7.5Hz, H-3), 5.13 (m, 2H,
H-4, H-2), 5.04 (d, 1H, J1,2 2.5Hz, H-1), 3.84 (m, 2H,
H-6, H-60), 3.58 (s, 3H, CH3O), 2.12, 2.07, (2s, 6H, ace-
tyl); 13C NMR (63MHz, CDCl3): d 170.3 (C@O), 170.2,
148.9 (C-5), 99.8, 98.0 (C-1, C-4), 69.0, 66.9 (C-2, C-3),
56.8 (CH3O), 29.5 (C-6), 21.0, 20.8 (acetyl). Anal. Calcd
for C11H15BrO6: C, 40.89; H, 4.68; O, 29.71. Found: C,
40.76; H, 4.55; O, 29.96.
(250MHz, CDCl3): d 4.86 (d, 1H, J1,2 3.5Hz, H-1),
4.54 (d, 1H, J6 ,5 1.0Hz, H-60), 4.37 (d, 1H, J6,5 1.0Hz,
0
0
H-6), 3.89 (ddd, 1H, J3,4 5.5, J3,2 8.5, J3,4 10.5Hz, H-
3), 3.55 (dd, 1H, J2,1 3.5, J2,3 8.5Hz, H-2), 3.47 (s, 3H,
CH3O), 2.69 (dd, 1H, J4 ,3 5.5, Jgem 13.5Hz, H-40),
0
0
2.25 (tdd, 1H, J4,6 = J4,6 1.0, J4,3 10.5, Jgem 13.5Hz,
H-4); 13C NMR (62.9MHz, CDCl3): d 153.06 (C-5),
100.18 (C-1), 97.22 (C-6), 73.73, 68.22 (C-2, C-3),
55.56 (CH3O), 36.17 (C-4); ESIMS (positive ion mode):
calcd for C7H12O4: (M+Na+), 183.0; found: m/z 183.0.
Anal. Calcd for C7H12O4: C, 51.49; H, 7.55. Found:
C, 51.78; H, 7.53.
3.4. Methyl 6-bromo-4,6-dideoxy-a-D-threo-hex-4-eno-
pyranoside (7)
LiOH (0.453g, 10.8mmol) was added to a soln of 6
(0.872g, 2.7mmol) in a 3:1 mixture of MeOH–water
(24mL). The suspension was stirred at rt for 5min, then
quenched with aq HCl (1.5M), and extracted with
CH2Cl2. The organic phase was dried (MgSO4) then
concentrated. Flash chromatography of the residue
(EtOAc) gave 7 (0.626g, 97%) as a colorless oil, which
decomposed slowly when kept at rt. 1H NMR
(250MHz, CDCl3): d 5.09 (d, 1H, J1,2 2.5Hz, H-1),
4.98 (d, 1H, J4,3 3.0Hz, H-4), 4.27 (dd, 1H, J3,4 3.0,
J3,2 7.5Hz, H-3), 3.85 (m, 2H, H-6, H-60), 3.71 (dd,
1H, J2,1 2.5, J2,3 7.5Hz, H-2), 3.59 (s, 3H, CH3O),
2.85 (br s, 2H, OH); 13C NMR (63MHz, CDCl3): d
147.2 (C-5), 103.5, 100.1 (C-1, C-4), 71.3, 67.0 (C-2, C-
3), 59.6 (CH3O), 30.2 (C-6). ESIHRMS (positive ion
mode): calcd for C7H11O4BrNa: 260.97385, found: m/z
260.97411.
3.6. 4-C-Acetyl-5-(S)-C-phenyl-4-deoxy-a,b-L-arabino-
pyranose (9a,b)
A soln of 8 (0.053g, 0.199mmol) was stirred at rt in aq
HCl (0.1M, 3mL) for 5min, then quenched with satd aq
NaHCO3, and extracted with CH2Cl2. The organic
phase was dried (MgSO4) and concentrated. Flash chro-
matography of the residue (EtOAc) gave a 1:3 mixture
of the two adducts 9a,b (0.045g, 90%) as a colorless oil.
Compound 9a (25%): 1H NMR (250MHz, CDCl3): d
7.46–7.21 (m, 5H, Ar), 5.44 (d, 1H, J5,4 3.0Hz, H-5),
5.37 (d, 1H, J1,2 3.0Hz, H-1), 4.33–4.20 (m, 2H, H-2,
H-3), 3.82 (m, 1H, H-4), 1.64 (s, 3H, CH3CO); 13C
NMR (63MHz, CDCl3): d 217.3 (C@O), 140.2, 131.6,
131.0, 128.3 (Ar), 95.6 (C-1), 76.8, 74.8, 72.3 (C-2, C-
3, C-5), 61.3 (C-4), 37.8 (CH3CO).

E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
2743
1
Compound 9b (75%): H NMR (250MHz, CDCl3): d
as a colorless oil followed by 26 (6mg, 7%) as a colorless
oil. Anal. Calcd for C14H20O8: C, 53.16; H, 6.37; O,
40.47. Found: C, 52.86; H, 6.42; O, 40.48.
7.46–7.21 (m, 5H, Ar), 4.91 (d, 1H, J5,4 2.9Hz, H-5),
4.66 (d, 1H, J1,2 7.5Hz, H-1), 4.10–3.94 (m, 2H, H-2,
H-3), 3.74 (m, 1H, H-4), 1.61 (s, 3H, CH3CO); 13C
NMR (63MHz, CDCl3): d 216.1 (C@O), 140.2, 131.6,
131.0, 128.3 (Ar), 100.0 (C-1), 75.0, 74.8, 71.2 (C-2, C-
3, C-5), 61.4 (C-4), 37.3 (CH3CO).
1
Compound 12a: H NMR (250MHz, CDCl3): d 5.39
(dd, 1H, J3,4 9.0, J3,2 10.2Hz, H-3), 5.05–4.94 (m, 2H,
H-1, H-2), 4.79 (d, 1H, H-60), 4.59 (m, 1H, H-6), 4.29
(dd, 1H, J7 ,4 6.0, Jgem 12.5Hz, H-70), 4.21 (dd, 1H,
0
J7,4 4.0, Jgem 12.5Hz, H-7), 3.45 (s, 3H, CH3O), 2.72
(m, 1H, H-4), 2.11–2.07 (m, 9H, CH3CO); 13C NMR
(63MHz, CDCl3): d 170.7, 170.2, 169.7, 152.0 (C-5),
98.4 (C-6), 97.6 (C-1), 71.8, 66.9 (C-2, C-3), 60.1 (C-7),
55.4 (CH3O), 43.2 (C-4), 20.7 (CH3CO).
3.7. 1,2,3-Tri-O-acetyl-4-C-acetyl-5-(S)-C-(phenyl)-4-
deoxy-a,b-L-arabinopyranose (10a,b)
A soln of 9a,b (45mg, 0.18mmol) in a mixture of 1:2
Ac2O–pyridine (1mL) was kept overnight at rt and con-
centrated. Flash chromatography of the residue (1:4
petroleum ether–EtOAc) gave 10a,b (66mg, 98%) as a
1:3 mixture of a and b anomers. Anal. Calcd for
C19H22O8: C, 60.31; H, 5.86; O, 33.83. Found: C,
60.29; H, 5.89; O, 33.17.
1
Compound 12b: H NMR (250MHz, CDCl3): d 5.43
(dd, 0.5H, J3,4 6.5, J3,2 10.0Hz, H-3), 5.11 (dd, 0.5H, J2,1
6.0, J2,3 10.0Hz, H-2), 5.05–4.94 (m, 2.5H, H-1), 4.70
(m, 1H, H-60), 4.50 (m, 1H, H-6), 4.27 (m, 2H, H-7,
H-70), 3.45 (s, 3H, CH3O), 3.22 (m, 1H, H-4), 2.11–
2.07 (m, 12H, CH3CO); 13C NMR (63MHz, CDCl3):
d 169.7, 170.1, 170.5 (C@O), 151.9 (C-5), 99.9 (C-6),
97.7 (C-1), 68.3, 67.6 (C-2, C-3), 61.3 (C-7), 55.5
(CH3O), 42.0 (C-4), 20.7 (CH3CO).
1
Compound 10a (25%): H NMR (250MHz, CDCl3):
d 7.40–7.22 (m, 5H, Ar), 6.84 (d, 1H, J1,2 4.0Hz, H-1),
6.08 (dd, 1H, J2,1 4.0, J2,3 10.0Hz, H-2), 5.54 (dd, 1H,
J3,4 6.0, J3,2 10.0Hz, H-3), 5.36 (d, 1H, J5,4 3.5Hz, H-
5), 3.81 (dd, 1H, J4,5 3.5, J4,3 6.0Hz, H-4), 2.35, 2.04,
2.03, 1.51 (4s, 12H, CH3CO); 13C NMR (63MHz,
CDCl3): d 204.8, 170.3, 169.6, 168.8 (C@O), 136.3,
128.2, 125.5 (Ar), 90.1 (C-1), 71.4, 68.7, 66.6 (C-2, C-
3, C-5), 55.8 (C-4), 34.0 (CH3CO), 20.9, 20.7, 20.5
(CH3COO). Compound 10b (75%): 1H NMR
(250MHz, CDCl3): d 7.40–7.22 (m, 5H, Ar), 6.00 (dd,
1H, J1,2 8.5, J2,3 9.5Hz, H-2), 5.79 (d, 1H, J1,2 8.5Hz,
H-1), 5.27 (dd, 1H, J3,4 6.0, J3,2 9.5Hz, H-3), 5.00 (d,
1H, J5,4 3.5Hz, H-5), 3.72 (dd, 1H, J4,5 3.5, J4,3
6.0Hz, H-4), 2.15, 2.06, 2.02, 1.55 (4s, 12H, CH3CO);
13C NMR (63MHz, CDCl3): d 204.2, 170.2, 169.3
(C@O), 136.0, 128.6, 125.3 (Ar), 92.8 (C-1), 74.6, 72.2,
68.4 (C-2, C-3, C-5), 55.8 (C-4), 33.7, 20.8, 20.6
(CH3CO).
3.9. Methyl 2,3-di-O-acetyl-4-C-[1-(S)-1-acetoxymethyl-
1-(30-O-benzyl-10,20-di-O-isopropylidene-40-(S)-C-a-D-
threofuranosyl)]-4,6-dideoxy-a-D-xylo-hex-5-enopyrano-
side (15)
Indium powder (69mg, 2mmol) was added to a soln of 7
(72mg, 0.3mmol) and aldehyde 13 (0.25g, 0.9mmol) in
a mixture of THF (0.6mL) and phosphate buffer (pH7,
0.11M, 0.3mL). After stirring for 1.5h, the mixture was
neutralized with satd aq NaHCO3. The suspension was
filtered over Celite, washed with EtOH and the filtrate
was concentrated. Flash chromatography (3:1–1:3
petroleum ether–EtOAc) gave starting aldehyde 13
(170mg) along with 14 (75mg, 57%) as a colorless oil
followed by 26 (9mg, 18%) as a colorless oil. Compound
14 was dissolved in 1:2 Ac2O–pyridine (3mL) and stirred
overnight. The solvents were coevaporated with toluene,
then flash chromatography (3:1 petroleum ether–
EtOAc) of the residue gave 15 (96mg, 99%) as a color-
3.8. Methyl 2,3-di-O-acetyl-4-C-[acetoxymethyl]-4,6-
dideoxy-a-D-xylo-hex-5-enopyranoside (12a) and methyl
2,3-di-O-acetyl-4-C-[acetoxymethyl]-4,6-dideoxy-b-L-
arabino-hex-5-enopyranoside (12b)
1
less oil; [a]D +52 (c 1.3, CH2Cl2); H NMR (250MHz,
0
0
CDCl3): d 7.48–7.32 (m, 5H, Ar), 5.97 (d, 1H, J1 ,2
0
Indium powder (115mg, 1mmol) was added to a soln of
7 (120mg, 0.5mmol) and formaldehyde (37% in water,
120lL, 1.5mmol) in a mixture of THF (1mL) and phos-
phate buffer (pH7, 0.15M, 0.38mL). After stirring for
3h, the mixture was neutralized with satd aq NaHCO3.
The suspension was filtered over Celite, washed with
EtOH and the filtrate was concentrated. Flash chroma-
tography (EtOAc) of the residue gave a mixture of 11a,b
(65mg, 73%) as a colorless oil, which was dissolved in
1:2 Ac2O–pyridine (3mL). After 15h, the solvents were
coevaporated with toluene, then flash chromatography
(3:1 petroleum ether–EtOAc) of the residue gave an
inseparable 16:9 mixture of 12a and 12b (111mg, 96%)
4.0Hz, H-10), 5.69 (dd, 1H, J7,4 3.0, J7,4 9.0Hz, H-7),
5.20 (t, 1H, J3,2 = J3,4 10.0Hz, H-3), 4.93 (br s, 1H, H-
60), 4.87 (d, 1H, J1,2 3.5Hz, H-1), 4.81 (br s, 1H, H-6),
4.79 (dd, 1H, J2,1 3.5, J2,3 10.0Hz, H-2), 4.74 (d, 1H,
Jgem 11.5Hz, PhCH2), 4.69 (d, 1H, J2 ,1 4.0Hz, H-20),
4.62 (dd, 1H, J4 ,3 3.5, J4 ,7 9.0Hz, H-40), 4.41 (d, 1H,
0
0
0
0
0
Jgem 11.5Hz, PhCH2), 3.89 (d, 1H, J3 ,4 3.5Hz, H-30),
3.42 (s, 3H, CH3O), 2.38 (dd, 1H, J4,7 3.0, J4,3 10.0Hz,
H-4), 2.07, 2.03, 1.99 (3s, 9H, CH3CO), 1.48, 1.33 (2s,
6H, C(CH3)2); 13C NMR (63MHz, CDCl3): d 170.3,
169.8, 169.5 (CH3CO), 149.9 (C-5), 136.3, 128.6, 128.3
(Ar), 111.6 (C(CH3)2), 104.8 (C-10), 102.0 (C-1), 98.0
(C-6), 81.7, 80.6, 78.5 (C-20, C-30, C-40), 72.7 (PhCH2),
0
0

2744
E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
71.4, 66.5, 65.7 (C-2, C-3, C-7), 55.6 (CH3O), 44.9 (C-4),
26.6, 26.1 (C(CH3)2), 20.9, 20.7, 20.6 (CH3CO). Anal.
Calcd for C28H36O12: C, 59.57; H, 6.43; O, 34.00.
Found: C, 59.32; H, 6.53; O, 34.28.
3.11. Methyl 2,3-di-O-acetyl-4-C-[(S)-1-O-acetyl-1-
(20,30,40,60-tetra-O-benzyl-b-D-glucopyranosyl)-methyl]-
4,6-dideoxy-a-D-xylo-hex-5-enopyranoside (20a), methyl
2,3-di-O-acetyl-4-C-[(S)-1-hydroxy-1-(20,30,40,60-tetra-O-
benzyl-b-D-glucopyranosyl)-methyl]-4,6-dideoxy-a-D-ara-
bino-hex-5-enopyranoside (21b)
3.10. 4-C-Acetyl-5-(S)-C-[30-O-benzyl-10,20-di-O-isopro-
pylidene-40-(S)-C-a-D-threofuranosyl]-4-deoxy-a,b-L-ara-
binopyranose (17a,b)
Indium powder (53mg, 0.46mmol) was added to a soln
of 7 (55mg, 0.23mmol) and aldehyde 18 (0.38g,
0.69mmol) in a mixture of THF (0.46mL) and phos-
phate buffer (pH7, 0.11M, 0.23mL). After stirring for
2h, the mixture was neutralized with satd aq NaHCO3.
The suspension was filtered over Celite, washed with
EtOH, and the filtrate was concentrated. Flash chroma-
tography (3:1–1:3 petroleum ether–EtOAc) of the resi-
due gave the starting aldehyde (248mg, 0.45mmol)
followed by a 16:9 mixture of 19a and 19b (74mg,
45%), and finally by 26 (11mg, 30%) as a colorless oil.
Compounds 19a,b (64:36): 1H NMR (250MHz,
CDCl3): d 3.07 (t, 0.55H, J4,3 = J4,7 6.0Hz, H-4(b)),
2.67 (t, 1H, J4,3 = J4,7 = 6.0Hz, H-4(a)); 13C NMR
(62.9MHz, CDCl3): d 154.5 (C-5(b)), 153.5 (C-5(a)),
138.5–137.0, 128.9–127.2 (Ar), 100.6 (C-1(a)), 100.2–
100.0 (C-1(b), C-6(b)), 98.7 (C-6(a)), 87.2 (C-10(b)),
87.1 (C-10(a)), 75.5, 75.4, 75.3, 75.0, 74.9, 73.4, 73.3
(CH2 benzyl (a,b)), 72.15, 72.0, 70.5, 69.3, 69.2, 68.65
(C-2(a,b), C-3(a,b), C-7(a,b), C-60(a,b)), 56.0 (OCH3
(a)), 55.8 (OCH3 (b)), 48.3 (C-4(a)), 48.0 (C-4(b)).
An aliquot of the 19:9 mixture of 19a,b (50mg,
0.07mmol) was added to a mixture of Ac2O (0.5mL)
and pyridine (1mL). After 16h at rt, the reaction mix-
ture was concentrated and flash chromatography of
the residue (4:1–3:2 petroleum ether–EtOAc) gave first
20a (51mg, 89%) followed by the partially acetylated
compound 20b (25mg, 81%). This latter was then fully
acetylated in 2:1 pyridine–Ac2O (1.5mL) at 40°C for
12h. The mixture was concentrated, and flash chroma-
tography of the residue (3:1 petroleum ether–EtOAc)
gave 21b (25mg, 95%) as a colorless oil.
A soln of 14 (0.092g, 0.21mmol) was stirred at rt in aq
HCl (0.1M, 2mL) for 30min, then quenched with a satd
aq NaHCO3 and extracted with CH2Cl2. The organic
phase was then dried (MgSO4) and concentrated. Flash
chromatography (1:4 petroleum ether–EtOAc) of the
residue gave 16a,b (11:9, 77mg, 86%) as a colorless oil.
This oil was then dissolved in 1:2 Ac2O–pyridine
(1.5mL), stirred overnight and coevaporated with tolu-
ene. Flash chromatography (4:1–3:2 petroleum ether–
EtOAc) of the residue gave a 11:9 mixture of a and b
anomers 17a,b (0.093g, 94%) as a colorless oil. Anal.
Calcd for C27H34O12: C, 58.90; H, 6.22; O, 34.88.
Found: C, 58.96; H, 6.41; O, 34.73.
Compound 17a: 1H NMR (250MHz, CDCl3): d 7.48–
7.34 (m, 5H, H-Ar), 6.45 (d, 1H, J1,2 4.0Hz, H-1), 5.90
(d, 1H, J1 ,2 4.0Hz, H-10), 5.61 (dd, 1H, J2,1 4.0, J2,3
10.5Hz, H-2), 5.38 (dd, 1H, J3,4 6.0, J3,2 10.5Hz, H-3),
4.73 (d, 1H, Jgem 11.5Hz, CH2C6H5), 4.69 (dd, 1H,
0
0
J2 ,3 1.0, J2 ,1 4.0Hz, 20-H), 4.44 (d, 1H, Jgem 11.5Hz,
0
0
0
0
0
CH2C6H5), 4.34 (dd, 1H, J5,4 2.5, J5,4 7.0Hz, H-5),
4.19 (dd, 1H, J4 ,3 4.5, J4 ,5 7.0Hz, H-40), 3.89 (dd,
0
0
0
1H, J3 ,2 1.0, J3 ,4 4.5Hz, H-30), 3.28 (dd, 1H, J4,5 2.5,
J4,3 6.0Hz, H-4), 2.06, 1.98, 1.91 (3s, 12H, CH3 acetyl),
1.45 (s, 3H, CH3), 1.33 (s, 3H, CH3). 13C NMR
(62.9MHz, CDCl3): d 205.3 (CO, ketone), 169.8,
169.6, 168.9 (CO, acetyl), 136.3, 129.1–128.3 (Ar),
112.7 ((CH3)2C), 105.0 (C-10), 89.8 (C-1), 82.3, 81.0,
79.1 (C-20, C-30, C-40), 71.5 (CH2C6H5), 70.2, 68.0,
66.7 (C-2, C-3, C-5), 50.8 (C-4), 33.3 (CH3, ketone),
27.1, 26.7 (isopropyl), 20.8, 20.7, 20.5 (acetyl).
0
0
0
0
Compound 17b: 1H NMR (250MHz, CDCl3): d
Compound 20a: [a]D +33 (c 1.2, CH2Cl2); H NMR
1
7.48–7.34 (m, 5H, Ar), 5.94 (d, 1H, J1 ,2 4.0Hz, H-10),
5.72 (d, 1H, J1,2 8.5Hz, H-1), 5.55 (dd, 1H, J2,1 8.5,
J2,3 10.0Hz, H-2), 5.17 (dd, 1H, J3,4 6.0, J3,2 10.0Hz,
H-3), 4.72 (d, 1H, Jgem 11.5Hz, CH2C6H5), 4.64 (d,
(250MHz, CDCl3): d 7.45–7.15 (m, 20H, H-Ar), 5.63
(dd, 1H, J7,1 3.0, J7,4 8.5Hz, H-7), 5.37 (dd, 1H, J3,4
5.5, J3,2 9.0Hz, H-3), 5.05–4.50 (m, 11H, 1-H, 2-H, H-
6b, CH2 benzyl), 4.37 (s, 1H, H-6a), 3.85–3.37 (m,
10H, CH3O, H-10, H-20, H-30, H-40, H-50, 2H-60), 3.04
(dd, 1H, J4,3 5.5, J4,7 8.5Hz, H-4), 2.06, 1.91, 1.82 (3s,
9H, Ac); 13C NMR (63MHz, CDCl3): d 170.2, 169.5
(CO), 151.5 (C-5), 138.4–138.1, 128.3–127.5 (Ar), 98.5
(C-6), 97.7 (C-1), 87.4 (C-10), 79.3, 79.2, 78.3, 76.5 (C-
20, C-30, C-40, C-50), 75.6, 75.0, 74.4, 73.2 (CH2 benzyl),
71.8, 70.9, 66.9 (C-2, C-3, C-7), 68.6 (C-60), 56.0
(CH3O), 46.2 (C-4), 20.9, 20.7, 20.6 (CH3 acetyl). Anal.
Calcd for C48H54O13: C, 68.72; H, 6.49; O, 24.79.
Found: C, 68.37; H, 6.55; O, 24.16.
0
0
1H, J2 ,1 4.0Hz, H-20), 4.43 (d, 1H, Jgem 11.5Hz,
0
0
CH2C6H5), 4.13 (dd, 1H, J3 ,4 3.5, J4 ,5 8.5Hz, H-40),
0
0
0
0
4.01 (dd, 1H, J5,4 2.5, J5,4 8.5Hz, H-5), 3.92 (d, 1H,
J4 ,3 3.5Hz, H-30), 3.08 (dd, 1H, J4,5 2.5, J4,3 6.0Hz,
H-4), 2.10, 2.09, 2.03, 2.02 (4s, 12H, CH3CO), 1.44 (s,
3H, CH3), 1.31 (s, 3H, CH3); 13C NMR (63MHz,
CDCl3): d 205.0 (CO ketone), 169.5, 168.8 (acetyl),
136.5, 128.4–128.7 (Ar), 112.2 ((CH3)2C), 105.2 (C-10),
92.7 (C-1), 81.8, 81.0, 79.0 (C-20, C-30, C-40), 73.0
(CH2C6H5), 71.7, 71.2, 69.0 (C-2, C-3, C-5), 51.8 (C-
4), 32.9 (CH3 ketone), 26.9, 26.4 (CH3), 20.9, 20.6
(acetyl).
0
0
1
Compound 20b: H NMR (250MHz, CDCl3): d 5.49
(dd, 1H, J2,3 10.0, J2,1 3.0Hz, H-2), 5.43 (dd, 1H, J3,2

E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
2745
10.0, J3,4 5.0Hz, H-3), 5.04 (d, 1H, J1,2 3.0Hz, H-1), 3.15
(t, 1H, J4,7 = J4,3 5.0Hz, H-4), 2.08 (s, 3H, CH3), 1.88 (s,
3H, CH3). ESIMS (positive ion mode): calcd for
30(a,b), C-40(a,b), C-50(a,b)), 75.43, 74.83, 74.41, 74.27,
73.24 (CH2Ph(a,b)), 74.22, 71.89, 71.08, 68.90, 68.77,
66.96, (C-2(a,b), C-3(a,b), C-5(a,b)), 68.60 (C-60(b)),
68.43 (C-60(a)), 49.17 (C-4(b)), 49.00 (C-4(a)), 34.08
(CH3CO(a)), 33.69 (CH3CO(b)), 20.74, 20.71, 20.66
(CH3COO(b)), 20.79, 20.63, 20.51 (CH3COO(a)). Anal.
Calcd for C47H52O13 (434.54): C, 68.43; H, 6.35; O,
25.21. Found: C, 68.58; H, 6.59; O, 25.21.
C46H52O12: (M+Na+), 819.3; found: m/z 819.4.
29
D
Compound 21b: ½aꢂ +63 (c 0.9, CH2Cl2); 1H
NMR (250MHz, CDCl3): d 7.45–7.15 (m, 20H, Ar),
5.78 (d, 1H, J 8.5Hz, H-7), 5.48 (dd, 1H, J3,4 6.0, J3,2
10.5Hz, H-3), 5.35 (dd, 1H, J2,1 3.5, J2,3 10.5Hz, H-2),
5.01 (d, 1H, J1,2 3.5Hz, H-1), 4.99–4.51 (m, 10H,
H-6a, H-6b, CH2 benzyl), 3.80–3.32 (m, 11H, CH3O,
H-10, H-20, H-30, H-40, H-50, H-6a0, H-6b0, H-4),
2.11, 2.08, 1.90 (3s, 9H, acetyl); 13C NMR (62.9MHz,
CDCl3): d 170.2–169.8 (acetyl), 151.4 (C-5), 138.4–
138.0, 128.5–127.5 (Ar), 102.3 (C-6), 98.0 (C-1), 87.7
(C-10), 79.5, 78.35, 78.1 (C-20, C-30, C-40, C-50), 75.6,
75.0, 74.9, 73.6 (CH2 benzyl), 69.0, 68.15 (C-2, C-3),
68.5 (C-60), 66.5 (C-7), 55.5 (CH3O), 44.7 (C-4),
21.05, 20.75, 20.7 (CH3CO). ESIMS (positive ion
mode): calcd for C48H54O13: (M+Na+), 861.3; found:
m/z 861.0.
3.13. 1,2,3-Tri-O-acetyl-4-C-acetyl-(S)-5-C-[20,30,40,60-
tetra-O-benzyl-b-D-glucopyranosyl]-4-deoxy-a,b-L-arabi-
nopyranose (25a,b)
LiOH (11mg, 0.27mmol) was added to a soln of com-
pound 21b (37mg, 44lmol) in 2:1 MeOH–water
(1.5mL). After 30min at rt, aq HCl (0.5M) was added
until neutrality and the mixture extracted with CH2Cl2
then concentrated. Aq HCl (0.1M, 1mL) was added
and the mixture was stirred for 2h at rt. After neutrali-
zation with satd aq NaHCO3, the mixture was extracted
with CH2Cl2, dried (MgSO4), and concentrated. Pyr-
idine–Ac2O (2:1, 3mL) was then added and after 16h
at rt, the reaction mixture was concentrated. Flash chro-
matography of the residue (4:1–2:1 petroleum ether–
EtOAc) gave a 4:5 mixture of a and b anomers 25a,b
(24mg, 77%) as a colorless oil. Anal. Calcd for
C47H52O13: C, 68.43; H, 6.35; O, 25.21. Found: C,
68.46; H, 6.61; O, 24.89.
Compound 25a: 1H NMR (250MHz, CDCl3): d 7.42–
7.15 (m, 20H, Ar), 6.21 (d, 1H, J1,2 3.5Hz, H-1), 6.00 (t,
1H, J3,2 = J3,4 8.0Hz, H-3), 4.98 (dd, 1H, J2,1 3.5,
J2,3 = 8.0Hz, H-2), 4.94.52 (m, 9H, H-5, CH2Ph),
3.81–3.51, 3.31–3.21 (m, 7H, H-10, H-20, H-30, H-40,
H-50, H-6a0, H-6b0), 3.08 (dd, 1H, J4,5 6.5, J4,3 8.0Hz,
H-4), 2.16, 2.09, 2.05, 1.91 (4s, 12H, acetyl); 13C NMR
(62.9MHz, CDCl3): d 202.71 (CO ketone), 170.19,
169.74, 169.41 (CO acetyl), 138.79, 138.66, 138.26,
138.19, 128.35, 127.19 (Ar), 91.07 (C-1), 86.75 (C-10),
79.90, 79.25, 77.96, 77.19 (C-20, C-30, C-40, C-50),
75.40, 75.10, 74.97, 73.49 (CH2Ph), 72.18, 71.03, 69.29
(C-2, C-3, C-5), 68.78 (C-60), 55.10 (C-4), 29.71 (CH3
ketone), 20.84, 20.79, 20.30 (acetyl).
Compound 25b: 1H NMR (250MHz, CDCl3): d
7.40–7.12 (m, 20H, Ar), 6.32 (dd, 1H, J3,4 10.5, J3,2
9.5Hz, H-3), 4.95 (dd, 1H, J2,1 8.5, J2,3 9.5Hz, H-2),
4.91–4.58 (m, 9H, H-5, CH2Ph), 4.12 (t, 1H, J 9.5Hz),
3.92–3.77 (m, 3H), 3.63 (t, 1H, J 9.5Hz), 3.25 (dd, 1H,
J4,3 10.5, J4,5 7.5Hz H-4), 3.39–3.17 (m, 2H), 2.18,
2.12, 1.97, 1.69 (4s, 12H, acetyl); 13C NMR
(62.9MHz, CDCl3): d 203.98 (CO ketone), 168.86,
168.11, 167.64 (acetyl), 138.28, 138.11, 137.66, 137.50,
128.45–127.25 (Ar), 90.07 (C-1), 85.96 (C-10), 79.53,
79.34, 78.88, 78.44 (C-20, C-30, C-40, C-50), 74.96,
74.46, 74.04, 73.79 (CH2Ph), 72.15, 71.18, 69.38, (C-2,
C-3, C-5), 68.68 (C-60), 55.05 (C-4), 29.78 (CH3 ketone),
20.65, 20.59, 20.30 (acetyl).
3.12. 1,2,3-Tri-O-acetyl-4-C-acetyl-(S)-5-C-[20,30,40,60-
tetra-O-benzyl-b-D-glucopyranosyl]-4-deoxy-a,b-L-arabi-
nopyranose (23a,b)
LiOH (16mg, 0.4mmol) was added to a soln of com-
pound 20a (55mg, 65lmol) in 2:1 MeOH–water
(1.5mL). After 30min at rt, aq HCl (0.5M) was added
until neutrality and the mixture was extracted with
CH2Cl2 then concentrated. Aq HCl (0.1M, 1mL) was
added and the mixture was stirred for 2h at rt. After
neutralization with sat aq NaHCO3, the mixture was ex-
tracted with CH2Cl2, dried (MgSO4), and concentrated.
A mixture of pyridine–Ac2O (2:1, 3mL) was then added
and after 16h at rt, the reaction mixture was concen-
trated. Flash chromatography of the residue (4:1–2:1
petroleum ether–EtOAc) gave a 12:8 mixture of a and
b anomers 23a,b (44mg, 82%) as a colorless oil. 1H
NMR (250MHz, CDCl3): d 7.42–7.10 (m, 32.8H, Ar),
6.46 (d, 1H, J1,2 4.0Hz, H-1(a)), 5.76 (dd, 1H, J2,1 4.0,
J2,3 10.5Hz, H-2(a)), 5.62 (dd, 0.64H, J2,1 8.5, J2,3
10.0Hz, H-2(b)), 5.52 (d, 0.64H, J1,2 8.5Hz, H-1(b)),
5.22 (dd, 1H, J3,4 6.0, J3,2 10.5Hz, H-3(a)), 4.93–4.41
0
(m, 13.8H, H-3(b), CH2Ph), 4.39 (t, 1H, J5,4 = J5,1
0
2.5Hz, H-5(a)), 3.78 (t, 0.64H, J5,4 = J5,1 2.5Hz, H-
5(b)), 3.74–3.33 (m, 11.4H, H-10(a,b), H-20(a,b), H-
30(a,b), H-40(a,b), H-50(a,b), H-6a0(a,b), H-6b0(a,b)),
3.21 (dd, 1H, J4,5 2.5, J4,3 6.0Hz, H-4(a)), 2.91 (dd,
0.64H, J4,5 2.5, J4,3 6.0Hz, H-4(b)), 2.12, 2.11, 2.03,
2.00, 1.97, 1.96 (8s, 20H, CH3COO and CH3CO); 13C
NMR (62.9MHz, CDCl3): d 205.15 (CO ketone (a)),
204.73 (CO ketone (b)), 169.87, 169.54, 169.25 (CO ester
(b)), 169.69, 169.39, 168.77 (CO ester(a)), 138.16–
137.55, 128.70–127.62 (Ar), 92.64 (C-1(b)), 90.33 (C-
1(a)), 86,65 (C-10(b)), 86.43 (C-10(a)), 78.81, 78.45,
78.39, 78.41, 78.37, 77.68, 77.55, 77.46 (C-20(a,b), C-

2746
E. Levoirier et al. / Carbohydrate Research 339 (2004) 2737–2747
3.14. Methyl 2,3,6-tri-O-acetyl-4-C-[(S)-1-O-acetyl-1-
(20,30,40,60-tetra-O-benzyl-b-D-glucopyranosyl)-methyl]-
a-L-idopyranoside (27)
(62.9MHz, CDCl3): d 170.47, 170.35, 170.13, 169.87
(CO), 138.42, 138.35, 138.05, 137.96, 128.61–127.45
(Ar), 97.11 (C-1), 87.31 (C-10), 81.91, 79.08, 78.25 (C-
20, C-30, C-40, C-50), 75.66, 75.13, 75.00, 73.34 (CH2Ph,
C-5), 70.20, 69.46, 68.31, 65.88, 65.20 (C-2, C-3, C-6,
C-7, C-60), 54.82 (OCH3), 42.30 (C-4), 21.26, 20.92,
20.83, 20.47 (CH3 acetyl). Anal. Calcd for C50H58O15:
C, 66.80; H, 6.50; O, 26.70. Found: C, 66.81; H, 6.76;
O, 26.66.
A 1M soln of BH3–THF complex in THF (0.20mL,
0.2mmol) was added to a cooled (0°C) soln of 20a
(34mg, 40lmol) in THF (0.5mL). The temperature
was then raised to rt and after 1h, a mixture of H2O2
(37% v/v, 0.2mL) and phosphate buffer (0.5M, pH7,
1mL) was added and the resulting mixture stirred for
1h at rt. CH2Cl2 (10mL) was then added and the mix-
ture was washed with water, dried (MgSO4), and con-
centrated. Then, 1:2 Ac2O–pyridine (3mL) was added
and after stirring for 12h, the reaction mixture was con-
centrated. Flash chromatography of the residue (4:1
Acknowledgements
´
We thank the Universite Paris-Sud and the CNRS for
`
funding as well as the Ministere de lÕEducation Nation-
ale et de la Recherche for a Ph.D. grant (E.L.)
petroleum ether–EtOAc) gave 27 (33mg, 91%) as a col-
29
D
orless oil. ½aꢂ +36 (c 1.1, CH2Cl2); 1H NMR (250MHz,
0
CDCl3): d 7.41–7.08 (m, 20H, Ar), 5.54 (dd, 1H, J7,1 4.0,
References
J7,4 3.5Hz, H-7), 5.41 (dd, 1H, J3,2 10.5, J3,4 10.0Hz, H-
3), 5.03–4.36 (m, 13H, H-1, H-2, H-5, 2H-6, CH2Ph),
3.44 (s, 3H, OMe), 3.78–3.37 (m, 7H, H-10, H-20, H-30,
H-40, H-50, 2H-60), 2.53 (ddd, 1H, J4,3 10.0, J4,5 5.0,
J4,7 3.5Hz, H-4), 2.03, 1.98, 1.88, 1.87 (4s, 12H, acetyl),
13C NMR (62.9MHz, CDCl3): d 170.75, 170.38, 170.18,
169.92 (CO), 138.17–137.92, 128.44–127.44 (Ar), 98.90
(C-1), 87.06 (C-10), 79.05, 78.73, 78.36, 77.90 (C-20, C-
30, C-40, C-50), 75.42, 74.93, 74.17, 73.21, 72.69 (CH2Ph,
C-5), 68.77 (C-60), 67.27 (C-7), 65.85, 64.73, 63.73 (C-2,
C-3, C-6), 56.76 (OMe), 43.21 (C-4), 20.94, 20.73, 20.57
(CH3 acetyl). Anal. Calcd for C50H58O15: C, 66.80; H,
6.50; O, 26.70. Found: C, 66.82; H, 6.66; O, 26.61.
´
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(20,30,40,60-tetra-O-benzyl-b-D-glucopyranosyl)-methyl]-
a-D-galactopyranoside (28)
A 1M soln of BH3–THF complex in THF (0.1mL,
0.1mmol) was added to a cooled (0°C) soln of 21b
(18mg, 21lmol) in THF (0.5mL). The temperature
was then raised to rt and after 1h, a mixture of H2O2
(37% v/v, 0.1mL) and phosphate buffer (0.5M, pH7,
1mL) was added and the resulting mixture stirred for
1h at rt. CH2Cl2 (10mL) was then added and the mix-
ture was washed with water, dried (MgSO4), and con-
centrated. Then, Ac2O–pyridine (1:2, 3mL) was added
and after stirring for 12h, the reaction mixture was con-
centrated. Flash chromatography of the residue (4:1
petroleum ether–EtOAc) gave 28 (16mg, 83%) as a col-
28
1
orless oil. ½aꢂ +88 (c 1.0, CHCl3); H NMR (250MHz,
D
CDCl3): d 7.45–7.08 (m, 20H, Ar), 5.87 (d, 1H, J7,4
3.0Hz, H-7), 5.49 (dd, 1H, J1,2 4.0, J2,3 10.5Hz, H-2),
5.25 (dd, 1H, J3,2 10.5, J3,4 5.5Hz, H-3), 5.01–4.36 (m,
12H, H-1, H-5, 2H-6, CH2Ph), 3.34 (s, 3H, OCH3),
3.75–3.29 (m, 6H, H-20, H-30, H-40, H-50, 2H-60), 2.91
(d, 1H, J1 ,2 9.5Hz, H-10), 2.81 (m, 1H, H-4), 2.17,
0
0
2.10, 2.02, 1.74 (4s, 12H, acetyl); 13C NMR

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