Syntheses of l-glucosamine donors for 1,2-trans-glycosylation reactions

Article abstract of DOI:10.1016/j.tetasy.2006.12.011

Two new l-glucosamine donors, that is pent-4-enyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-β-l-glucopyranos ide 16 and ethyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-1-thio-β-l-gluco pyranoside 21 were prepared in 12 steps from l-arabinose. The reaction pathway uses 3,4,6-tri-O-acetyl-l-glucal 5, and then 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-α-l-mannopyranosyl azide 8 as intermediates. The latter, together with donors 16 and 21, were used for preparing l-glucosamine neoglycolipids.

Full text of DOI:10.1016/j.tetasy.2006.12.011

Tetrahedron: Asymmetry 17 (2006) 3368–3379
Syntheses of L-glucosamine donors for
1,2-trans-glycosylation reactions
Dominique Lafont and Paul Boullanger*
Universite´ de Lyon, France; Chimie Physique Electronique de Lyon, Laboratoire de Chimie Organique II-Glycochimie,
CNRS UMR 5181, Universite Lyon 1, 43 boulevard du 11 Novembre 1918,
F-69622 Villeurbanne Cedex, France
Received 3 November 2006; accepted 10 December 2006
Available online 16 January 2007
Abstract—Two new L-glucosamine donors, that is pent-4-enyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-b-L-glucopyranoside
16 and ethyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-1-thio-b-L-glucopyranoside 21 were prepared in 12 steps from L-arab-
inose. The reaction pathway uses 3,4,6-tri-O-acetyl-L-glucal 5, and then 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-a-L-mannopyranosyl azide 8 as
intermediates. The latter, together with donors 16 and 21, were used for preparing L-glucosamine neoglycolipids.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
bear one stereogenic center only. In the field of glycolipids,
in which the hydrophilic head contains several stereogenic
centers, mostly aldonamides were studied. Thus, it was
demonstrated that epimers could behave quite differently,
N-dodecyl gluconamide exhibiting an heterochiral prefer-
ence whereas N-dodecyl mannonamide exhibited an homo-
chiral preference.4
Chiral discrimination in self-organized supramolecular sys-
tems is of major importance in understanding the building
of biological assemblies, such as cell membranes. Amongst
such assemblies, monolayers constitute a very simple 2D
cell membrane model that was studied in detail.1 In these
simple systems, the chirality of the molecules can induce
the formation of chiral anisotropic domains that can be
displayed in the p-A isotherm or directly visualized in the
condensed phase by Brewster angle microscopy (BAM)2
or fluorescence microscopy,3 for example. The chiral dis-
crimination can manifest itself in two ways: either the chi-
ral molecules have a higher affinity for themselves than for
the enantiomer, thus forming aggregates in the condensed
phase (homochiral discrimination), or the chiral molecules
have a higher affinity for their enantiomers (heterochiral
discrimination). In the latter case, the racemic mixture dis-
plays lower surface areas than the pure enantiomers at any
surface pressures. Many amphiphilic molecules able to
form such assemblies have been studied, most of which
In the field of our research devoted to the use of N-acetyl-
D-glucosaminyl neoglycolipids I in the formation of stable
monolayers, able to strongly embed immunoglobulins in an
oriented position, we were surprised by such a stability.5
Amongst the hypotheses put forward to explain this phe-
nomenon, a carbohydrate–carbohydrate recognition be-
tween the glycolipid head and the glycan fraction of the
immunoglobulin could be responsible for the interaction.
The assembly was modeled and shown to be compatible
with the hypothesis.6 Consequently, we decided to build
monolayers with molecules of opposite chirality, that is
N-acetyl-L-glucosamine neoglycolipids II, in order to check
the stability of embeddement of immunuglobulins in the
OH
OCnH2n+1
HO
OCnH2n+1
OCnH2n+1
O
(OCH2CH2)3O
NHAc
HO
HO
O
(OCH2CH2)3O
OCnH2n+1
HO
NHAc
OH
I
II
*
Corresponding author. Tel.: +33 4 72 43 11 62; e-mail: paul.boullanger@univ-lyon1.fr
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.12.011

D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
3369
latter and also to study the chiral discrimination between
both enantiomers of the glycolipid. Herein, we report the
synthesis of such neoglycolipids.
4a/4b. Treatment of the mixture with hydrobromic acid,
followed by zinc reduction, afforded 3,4,6-tri-O-acetyl-L-
glucal 5 in 88% from 4a/4b (Scheme 1).
The iodoacetoxylation22 of 5 (I2, Cu(OAc)2, AcOH, 80 ꢁC)
afforded 1,3,4,6-tetra-O-acetyl-2-deoxy-2-iodo-b-L-gluco-
pyranose 6 and 1,3,4,6-tetra-O-acetyl-2-deoxy-2-iodo-a-L-
mannopyranose 7 in 11% and 79% yields, after purifica-
tion. Iodoacetate 7 was then converted to the 2-iodoglyco-
syl azide 8 (TMSN3, TMSOTf, CH2Cl2) in 94% yield, by
the methodology that we have already reported in the D-
series.23 The latter was used as glycosylation donor, using
the procedure described previously (PPh3, CH2Cl2),24 with
cholesterol or 10-undecyloxymethyl-3,6,9,12-tetraoxatri-
cosanol 1025 as acceptors to afford 2-acetamido-2-deoxy
L-glycosides 9 and 11 in 62% and 51% yields, respectively.
Nevertheless, this procedure is only efficient with reactive
acceptors, as mentioned previously in the D-series. There-
fore, we were searching for more efficient glycosylation
donors of L-glucosamine from intermediate 8.
2. Results and discussion
Due to the low occurrence of the L-enantiomer (only found
as N-methyl derivatives in streptomycines7) compared with
the D-enantiomer found in many natural compounds and
biopolymers such as glycoproteins or chitins,8 very few syn-
theses of L-glucosamine derivatives have been reported in
the literature. Formerly, L-arabinose and hydrogen cyanide
were used to prepare a 2-alkylamino-2-deoxy-L-glucono-
nitrile, which was further transformed into N-alkyl-L-gluco-
samine by controlled hydrogenation.9–12 In 1989, Leblanc
et al.13 reported the [4+2] cycloaddition of dibenzyl azodi-
carboxylate and glycals. Thus methyl 2-acetamido-2-
deoxy-3,4,6-tri-O-acetyl-b-L-glucopyranoside was prepared
from a furanic L-glycal, thus avoiding the use of hydrogen
cyanide. Azidonitration of tri-O-acetyl-L-glucal was
reported to afford a mixture of separable 2-azido-2-deoxy-
L-manno and -L-gluco epimers, each obtained in 38%
yield;14 the latter could be subsequently transformed into
N-acetyl derivatives. In 2000, Sasaki et al.15 reported an
eight step synthesis of a 3-O-tert-butylsilyl derivative of
L-glucosamine from 2,3-O-isopropylidene-L-glyceraldehyde
and (R)-2-tert-butyloxycarbonylamino-3-phenylsulfonyl-
1-propanol. More recently, using the ‘mirror-image carbo-
hydrate’ concept,16 Boulineau and Wei17,18 reported the
synthesis of non-natural enantiomers of lactosamine and a
trisaccharide blood group. The key step was the iodosulfon-
amidation of L-glucal, followed by glycosylation using
Danishefsky’s procedure.19,20
Several D-glucosamine donors for 1,2-trans-glycosylation
have been reviewed in the literature,26–28 which could be
extended to L-glucosamine donors. We experienced 2-
alkoxycarbonylamino derivatives, previously used in our
laboratory, since they allow the use of a large variety of
anomeric leaving groups and constitute as versatile deriva-
tives for further transformations on the amino function. A
pentenyl glycoside donor29,30 was prepared by the reaction
of 8 with pent-4-en-1-ol in the presence of PPh3, as
reported previously, to afford 12 in 71% yield (Scheme 2).
The unreactive acetamido function of 12 was then activated
via a 2-amino-2-deoxy intermediate 15 by the following
pathway: treatment with tert-butyl pyrocarbonate in the
presence of DMAP in THF31 afforded the N-acetyl, N-
tert-butoxycarbonyl compound 13 (93%) as a mixture of
two rotamers.32 Then de-O,N-acetylation and re-O-acetyl-
ation afforded the NHBoc derivative 14 (92%), which
was deprotected quantitatively to give the free amino deriv-
ative 15 using trifluoroacetic acid. The latter can then be
activated in several manners; we chose the reaction of allyl-
chloroformate under biphasic conditions (CHCl3/H2O), in
We decided to explore a new strategy to prepare L-glucos-
amine glycosylation donors by simple methods that could
be scaled up. Thus, the condensation of L-arabinose 1 with
nitromethane, in the presence of sodium methylate21 affor-
ded a mixture of 1-deoxy-1-nitro-L-glucitol 2a and 1-
deoxy-1-nitro-L-mannitol 2b. The acidic treatment (Nef
reaction) of the mixture 2a/2b gave rise to a mixture of
L-glucose and L-mannose 3a/3b, which was acetylated to
NO2
R2
R1
RO
OR
CHO
OH
O
R1
OH
RO
a
b
RO
R2
HO
HO
HO
HO
3a. R=H, R1=OH, R2=H
CH2OH
3b. R=H, R1=H, R2=OH
CH2OH
c
4a. R=Ac, R1=OAc, R2=H
2a. R1=OH, R2=H
2b. R1=H, R2=OH
c
1
4b. R=Ac, R1=H, R2=OAc
Br
AcO
O
AcO
AcO
d
e
O
AcO
R1
4a + 4b
AcO
AcO
R2
5
Scheme 1. Reagents and conditions: (a) MeNO2, MeONa, MeOH, 50%; (b) H2SO4, then Dowex [H]+, 78%; (c) Ac2O, pyridine, 74%; (d) 33% HBr in
AcOH, Ac2O, 100%; (e) Zn powder, CuSO4, AcONa, 60% aq AcOH, 88%.

3370
D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
OAc
AcO
AcO
AcO
AcO
AcO
AcO
OAc
I
O
O
O
a
+
AcO
AcO
I
AcO
5
7
6
N3
AcO
AcO
AcO
XR
NR1R2
O
b
c
O
7
AcO
AcO
AcO
I
8
9 R1, R2= H, Ac, X = O, ROH = Cholesterol
11 R1, R2= H, Ac, X = O, ROH = 10
12 R1, R2= H, Ac, X = O, R = pent-4-enyl
17 R1, R2= H, Ac, X = S, R = Et
OCnH2n+1
OCnH2n+1
H(OCH2CH2)3O
d
e
10. n = 11
22. n = 14
13 R1, R2=Ac, Boc, X = O, R = pent-4-enyl
18 R1, R2=Ac, Boc, X = S, R = Et
14 R1, R2=H, Boc, X = O, R = pent-4-enyl
19 R1, R2=H, Boc, X = S, R = Et
d
OC11H23
OC11H23
HO
e
24
f
15 R1, R2=H, X = O, R = pent-4-enyl
20 R1, R2=H, X = S, R = Et
f
g
16 R1, R2=H, Aloc, X = O, R = pent-4-enyl
21 R1, R2=H, Aloc, X = S, R = Et
g
h, 22
23 R1, R2=H, Aloc, X = O, ROH = 22
25 R1, R2=H, Aloc, X = O, ROH = 24
h, 24
AcO
HO
OR
OR
NHAc
O
O
NHR1
AcO
HO
AcO
HO
j
j
9
R1= Ac, ROH = Cholesterol
28 ROH = Cholesterol
29 ROH = 10
11 R1= Ac, ROH = 10
23 R1= Aloc, ROH = 22
26 R1= Ac, ROH = 22
25 R1= Aloc, ROH = 24
27 R1= Ac, ROH = 24
i
i
j
30 ROH = 22
31 ROH = 24
j
Scheme 2. Reagents and conditions: (a) I2, Cu(OAc)2, AcOH, 80 ꢁC (11% 6, 79% 7); (b) TMSN3, TMSOTf, CH2Cl2, 94%; (c) (I) ROH or EtSH, PPh3,
CH2Cl2, (II) Dowex 2X8 [OHÀ], EtOH, (III) MeONa (cat.), MeOH, (IV) Ac2O, pyridine (62% 9, 51% 11, 71% 12, 43% 17); (d) Boc2O, DMAP (cat.),
THF, 80 ꢁC (93% 13, 90% 18); (e) (I) MeONa (cat.), MeOH, (II) Ac2O, pyridine (92% 14, 90% 19); (f) TFA, CH2Cl2 (100% 15 and 20); (g) AllOCOCl,
NaHCO3, CHCl3, H2O (90% 16, 95% 21); (h) ROH, NIS, TMSOTf, CH2Cl2, À20 ꢁC; (i) (I) Pd(PPh3)4, CH2(COOEt)2, THF; (II) Ac2O, pyridine (77% 26,
81% 27); (j) MeONa (cat.), MeOH, 93–95%.
the presence of NaHCO3, which afforded donor 16 in 90%
yield, that is 72% overall yield from compound 12. The
same reaction pathway was applied to prepare a thioalkyl
glycosyl donor.33 The Staudinger reaction of 8 and ethane-
thiol affording 17 was accompanied by several by-products
(43% yield only). Further transformations of N-acetyl
derivative 17 to N-Boc derivative 19, then to the free amino
compound 20, and finally to ethyl 3,4,6-tri-O-acetyl-2-allyl-
oxycarbonylamino-2-deoxy-1-thio-b-L-glucopyranoside 21
were realized, as previously, in 73% overall yield.
pounds 12 and 17 to (thio)alkyl 2-amino-2-deoxy-L-gluco-
sides, followed by N-carbamoylation, then O-acetylation.
Despite its simplicity, this reaction pathway afforded sev-
eral by-products, which were difficult to separate from
the expected intermediates. Therefore, the four step reac-
tions from 12 and 17 to 16 and 21, respectively, were pre-
ferred to the latter.
Glycosylation reactions from L-donors 16 and 21, as
well as their D-enantiomers, and two acceptor alcohols
(10-tetradecyloxymethyl-3,6,9,12-tetraoxahexacosanol34 22
and 1,3-bis(undecyloxy)propan-2-ol25 24) were then real-
ized under the usual conditions, in order to demonstrate
It should be noted that a shorter route to compounds 16
and 21 was also explored, that is saponification of com-

D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
3371
the feasibility of this method. Thus, glycoside 23 (81%
yield) was obtained via reaction of 16 with 22 in the pres-
ence of stoichiometric amounts of N-iodosuccinimide and
trimethylsilyl triflate, whereas glycoside 25 (76% yield)
was obtained by reaction of 21 with 24 under the same con-
ditions. The enantiomeric glycoside of 25 (25-D) was also
prepared in 74% yield, by reaction of the enantiomeric
donor of 16 (16-D) and acceptor alcohol 24, under the
same conditions.
(20 mL). After dissolving the solid in H2O (75 mL), the
solution was eluted with water through a column of Dow-
ex 50WX4 [H+] resin. After concentration, the residue was
co-evaporated twice from EtOH (2 · 100 mL), and crystal-
lized on standing overnight at À15 ꢁC in absolute EtOH
(75 mL). Filtration afforded a mixture of 1-deoxy-1-
nitro-L-glucitol 2a and 1-deoxy-1-nitro-L-mannitol 2b
(14.0 g, 50%). Compound 2a: 13C NMR (D2O): d 78.8
(C-1), 71.5 (C-5), 71.1 (C-4), 70.7 (C-2), 70.4 (C-3),
63.2 (C-6). Compound 2b: 13C NMR (D2O): d 79.7 (C-
1), 70.7 (C-5), 70.5 (C-3), 69.4 (C-4), 69.0 (C-2), 63.7
(C-6).
Glycosides 9, 11, 23, 25, and 25-D were fully deprotected
affording products 28–31 and 31-D in good yields.
A solution of nitrosugars 2a/2b (14.0 g, 66.3 mmol) in 2 M
NaOH (42.1 mL, 84.2 mmol) was added dropwise to a stir-
red solution of 7.3 M H2SO4 (46.6 mL, 0.68 mol). After
30 min, the solution was diluted with water (400 mL), then
neutralized with warm aq Ba(OH)2. After centrifugation
and addition of a slight excess of aq Ba(OAc)2 to the super-
natant, the solution was filtered through Celite, concen-
trated to 200 mL, and deionized on a column of Dowex
50WX4 [H+]. The L-glucose/L-mannose mixture 3a/3b
was obtained as a white powder after evaporation and
co-evaporation from absolute EtOH (2 · 100 mL) and
was pure enough for the next step (9.3 g, 78%). Compound
3aa: 13C NMR (D2O): d 92.5 (C-1), 73.2 (C-3), 71.9, 71.8
(C-2, C-5), 70.1 (C-4), 61.1 (C-6). Compound 3ab: 13C
NMR (D2O): d 96.3 (C-1), 76.3, 76.2 (C-3, C-5), 74.6 (C-
2), 70.0 (C-4), 61.2 (C-6). Compound 3ba: 13C NMR
(D2O): d 94.5 (C-1), 72.8 (C-5), 71.1 (C-2), 70.7 (C-3),
67.3 (C-4), 61.4 (C-6). Compound 3bb: 13C NMR (D2O):
d 94.1 (C-1), 76.6 (C-5), 73.5 (C-3), 71.6 (C-2), 67.1 (C-4),
61.4 (C-6).
3. Conclusion
The reaction pathway depicted herein allowed us to pre-
pare the expected 2-acetamido-2-deoxy-b-L-glucopyranosyl
neoglycolipids in reasonable yields, without using toxic
derivatives, such as hydrogen cyanide. The glycosylations
with donors 16 and 21 were shown to be of great synthetic
interest, as previously demonstrated for their D-counter-
parts. They can be used for the preparation of other unnat-
ural derivatives of L-glucosamine. The study of chiral
discrimination in the monolayers of I and II is now
under investigation and the results will be reported in due
course.
4. Experimental
4.1. General methods
Pyridine was dried by boiling with CaH2 prior to distilla-
tion. Dichloromethane was washed twice with water, dried
with CaCl2, and distilled from CaH2. Methanol was dis-
tilled from magnesium. Tetrahydrofuran was distilled from
sodium-benzophenone. Pyridine, THF, and CH2Cl2 were
stored over 4 A molecular sieves and MeOH over 3 A
molecular sieves. Melting points were determined on a
Buchi apparatus and are uncorrected. Thin layer chromato-
¨
graphy was performed on aluminum sheets coated with
Silica gel 60 F254 (E. Merck). Compounds were visualized
by spraying the TLC plates with dilute 15% aq H2SO4, fol-
lowed by charring at 150 ꢁC for a few minutes. Column
chromatography was performed on Silica-gel Geduran Si
60 (Merck). Optical rotations were recorded on a Perkin
Elmer 241 polarimeter in a 1 dm cell at 21 ꢁC. 1H and
13C NMR spectra were recorded with a Bruker AC-200
spectrometer working at 200 and 50 MHz, respectively,
with Me4Si as internal standard. Elemental analyses were
performed by the ‘Laboratoire Central d’Analyses du
CNRS’ (Vernaison, France).
4.3. Mixture of 1,2,3,4,6-penta-O-acetyl-L-glucopyranose 4a
and L-mannopyranose 4b
˚
˚
The mixture 3a/3b (6.0 g, 33.3 mmol) was added at 0 ꢁC to
a stirred solution of pyridine (60 mL) and acetic anhydride
(50 mL). The solution was allowed to reach room temper-
ature and stirring was maintained for 16 h. After concen-
tration, the residue was dissolved in CH2Cl2 (150 mL)
and the organic solution was washed with 10% aq HCl
(25 mL), then with satd aq NaHCO3 (250 mL) and finally
with water. After drying and evaporation, the product
was purified by column chromatography (4:5 EtOAc–
petroleum ether) to afford the expected mixture 4a/4b as
an oily material (9.6 g, 74%). Rf = 0.72 (EtOAc–petroleum
ether 1:1); 1H NMR (CDCl3): d 6.31 (d, 0.32 H, J = 3.6 Hz,
H-1a-glc), 6.08 (d, 0.25H, J = 1.6 Hz, H-1a-man), 5.86 (br s,
0.15H, H-1b-man), 5.71 (d, 0.27H, J = 7.8 Hz, H-1b-glc),
5.50–5.05 (m, 3H, H-2, H-3, H-4), 4.35–4.01 (m, 2H, H-
6a, H-6b), 3.87–3.72 (m, 1H, H-5), 2.17–2.00 (m, 15H,
5CH3COO). Compound 4aa: 13C NMR (CDCl3): d 88.9
(C-1), 69.7 (C-3, C-5), 69.1 (C-2), 67.8 (C-4), 61.4 (C-6).
Compound 4ab: 13C NMR (CDCl3): d 91.6 (C-1), 72.6,
72.5 (C-3, C-5), 69.7 (C-2), 67.7 (C-4), 61.4 (C-6). Com-
pound 4ba: 13C NMR (CDCl3): d 90.5 (C-1), 70.3 (C-5),
68.7 (C-2), 68.2 (C-3), 65.4 (C-4), 62.0 (C-6). Compound
4bb: 13C NMR (CDCl3): d 90.3 (C-1), 73.0 (C-5), 69.7
(C-4), 68.1 (C-2), 65.4 (C-3), 62.0 (C-6).
4.2. Mixture of L-glucose 3a and L-mannose 3b
To a suspension of L-arabinose 1 (20.0 g, 133 mmol) in a
mixture of anhydrous MeOH (40 mL) and nitromethane
(72 mL) was added a solution of MeONa (10.0 g,
185 mmol) in dry MeOH (120 mL). The suspension was
stirred for 48 h, then filtered, and the filter cake washed
exhaustively with cold MeOH (200 mL), and then Et2O

3372
D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
4.4. 3,4,6-Tri-O-acetyl-1,5-anhydro-2-deoxy-L-arabino-hex-
1-enitol 5
H-6b), 4.12 (ddd, 1H, J = 9.8, 4.4, 2.4 Hz, H-5), 2.17,
2.12, 2.11, 2.07 (4s, 12H, CH3COO); 13C NMR (CDCl3):
d 170.5, 169.8, 169.3, 168.1 (CH3COO), 94.6 (C-1), 71.4
(C-5), 68.6 (C-3), 67.0 (C-4), 61.8 (C-6), 27.3 (C-2), 20.8,
20.8, 20.7, 20.6 (CH3COO). Anal. Calcd for C14H19IO9
(458.192): C, 36.69; H, 4.18. Found: C, 37.01; H, 4.21.
A mixture of 4a/4b (9.2 g, 23.5 mmol) was dissolved in
AcOH (15 mL) and Ac2O (3 mL), then 33% HBr in acetic
acid (25 mL) was added at room temperature. After 16 h,
the solution was cooled to 0 ꢁC, neutralized with anhy-
drous AcONa (10.0 g, 121.9 mmol) and then added to a
mixture of CuSO4Æ5H2O (1.55 g, 6.2 mmol), zinc powder
4.6. 3,4,6-Tri-O-acetyl-2-deoxy-2-iodo-a-L-mannopyranosyl
azide 8
(37.8 g,
578 mmol),
and
AcONaÆ3H2O
(47.3 g,
347.5 mmol) in water (50 mL) and AcOH (75 mL). After
vigourous stirring for 1.5 h at room temperature, the mix-
ture was filtered and the filter cake was washed with EtOAc
(150 mL), and then H2O (150 mL). The aq filtrate was ex-
tracted with EtOAc (2 · 75 mL) and the combined organic
phases were washed with satd aq NaHCO3 until neutral.
After drying over Na2SO4 and concentration, the residue
was purified by flash column chromatography (1:4
EtOAc–petroleum ether, 0.5% NEt3) to afford the expected
compound 5 as a colorless oil (5.6 g, 88%). [a]D = +22.0 (c
1.2, CHCl3) [D-enantiomer: lit.35 [a]D = À22 (c 2.1,
CHCl3)]; 1H NMR (CDCl3) d 6.47 (dd, 1H, J = 6.1,
1.0 Hz, H-1), 5.30 (m, 1H, H-3), 5.22 (dd, 1H, J = 5.8,
7.2 Hz, H-4), 4.85 (dd, 1H, J = 6.1, 3.2 Hz, H-2), 4.42
(dd, 1H, J = 5.3, 11.8 Hz, H-6a), 4.26 (ddd, 1H, J = 7.2,
5.4, 2.7 Hz, H-5), 4.20 (dd, 1H, J = 2.7, 11.8 Hz, H-6b),
2.10, 2.08, 2.05 (3s, 9H, 3CH3COO).
Trimethylsilyl
trifluoromethanesulfonate
(0.360 mL,
1.86 mmol) was added under argon to a solution of com-
pound 7 (5.50 g, 12.00 mmol) and Me3SiN3 (3.0 mL,
22.40 mmol) in dry CH2Cl2 (25 mL). The mixture was stir-
red for 24 h, diluted with CH2Cl2 (100 mL), and neutral-
ized by the addition of an excess of satd aq NaHCO3
and stirring for 2 h. The aqueous solution was extracted
with CH2Cl2 (2 · 60 mL) and the combined organic phases
were dried over Na2SO4, concentrated under reduced pres-
sure, and purified by column chromatography (1:1 EtOAc–
petroleum ether).
Compound 8 was obtained as a syrup (4.98 g, 94%);
[a]D = À81.8 (c 1.0, CHCl3); 1H NMR (CDCl3): d 5.71
(d, 1H, J = 1.2 Hz, H-1), 5.36 (dd, 1H, J = 8.6, 9.5 Hz,
H-4), 4.52 (dd, 1H, J = 4.3, 8.6 Hz, H-3), 4.48 (dd, 1H,
J = 1.2, 4.3 Hz, H-2), 4.26 (dd, 1H, J = 4.9, 12.4 Hz, H-
6a), 4.22–4.18 (m, 2H, H-5, H-6b), 2.13, 2.10, 2.07 (3s,
9H, 3CH3COO); 13C NMR (CDCl3): d 170.5, 169.6,
169.3 (CH3COO), 91.0 (C-1), 71.4 (C-5), 68.6 (C-3), 67.1
(C-4), 61.8 (C-6), 28.0 (C-2), 20.9, 20.7, 20.6 (CH3COO).
Anal. Calcd for C12H16IN3O7 (441.169): C, 32.67; H,
3.66; N, 9.52. Found: C, 32.73; H, 3.66; N, 9.18.
4.5. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-b-L-glucopyra-
nose 6 and 1,3,4,6-tetra-O-acetyl-2-deoxy-2-iodo-a-L-
mannopyranose 7
A mixture of 5 (5.45 g, 20.00 mmol), Cu(OAc)2ÆH2O
(4.39 g, 22.00 mmol), and iodine (6.09 g, 24.00 mmol) in
AcOH (120 mL) was stirred for 4 h at 80 ꢁC. The mixture
was cooled to room temperature and concentrated under
reduced pressure. The residue was diluted with EtOAc
(250 mL) and the solution neutralized with satd aq Na-
HCO3, then treated with satd aq Na2S2O3 (50 mL) and
finally with water (50 mL). The organic solution was dried
(Na2SO4), concentrated, and purified by flash column
chromatography (1:2 EtOAc–petroleum ether) affording
compounds 6 (1.01 g, 11%) and 7 (7.24 g, 79%).
4.7. Cholesteryl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-L-
glucopyranoside 9
A solution of L-glycosyl donor 8 (0.180 g, 0.41 mmol) and
cholesterol (0.174 g, 0.45 mmol) in CH2Cl2 (3 mL) was
cooled to 10 ꢁC before the addition of PPh3 (0.118 g,
0.45 mmol). The mixture was allowed to reach room tem-
perature and stirring was maintained overnight. After con-
centration, the residue was dissolved in the minimum
amount of EtOH and was then applied at the top of a col-
umn of Dowex 2X8 [OHÀ]. After elution with EtOH and
concentration, the residue was treated overnight by a cata-
lytic amount of MeONa in MeOH (5 mL). The alcoholic
solution was concentrated under diminished pressure and
the residue acetylated overnight in a 2:1 pyridine–Ac2O
mixture (5 mL). The solution was then concentrated and
purified by column chromatography (EtOAc). Compound
9 was recrystallized from absolute EtOH and obtained as
a white crystalline material (0.180 g, 62%). Mp 227 ꢁC; Rf
0.62 (EtOAc); [a]D = À14.1 (c 1.0, CHCl3); 1H NMR
(CDCl3): d 5.56 (d, 1H, J = 8.5 Hz, NH), 5.43 (dd, 1H,
J = 10.1, 9.4 Hz, H-3), 5.37 (m, 1H, H-6Chol), 5.05 (dd,
1H, J = 9.4, 9.9 Hz, H-4), 4.90 (d, 1H, J = 8.2 Hz, H-1),
4.28 (dd, 1H, J = 4.7, 12.1 Hz, H-6a), 4.12 (dd, 1H,
J = 1.9, 12.1 Hz, H-6b), 3.73 (ddd, 1H, J = 9.9, 4.7,
1.9 Hz, H-5), 3.64 (ddd, 1H, J = 8.2, 10.1, 8.5 Hz, H-2),
3.50–3.48 (m, 1H, H-3Chol), 2.09, 2.06, 2.03, 1.96 (4s,
12H, 4CH3CO), 3.38–0.68 (m, 43H, H cholesterol); 13C
Compound 6: white solid; mp 108 ꢁC; [a]D = À64.5 (c 1.0,
1
CHCl3); H NMR (CDCl3): d 5.87 (d, 1H, J = 9.6 Hz, H-
1), 5.35 (dd, 1H, J = 11.1, 9.0 Hz, H-3), 5.01 (dd, 1H,
J = 9.0, 10.1 Hz, H-4), 4.33 (dd, 1H, J = 4.4, 12.5 Hz, H-
6a), 4.08 (dd, 1H, J = 2.2, 12.5 Hz, H-6b), 3.98 (dd, 1H,
J = 9.6, 11.1 Hz, H-2), 3.89 (ddd, 1H, J = 10.1, 4.4,
2.2 Hz, H-5), 2.17, 2.09, 2.05, 2.02 (4s, 12H, 4CH3COO);
13C NMR (CDCl3):
d 170.4, 169.4, 169.4, 168.4
(CH3COO), 93.8 (C-1), 75.1 (C-5), 72.9 (C-3), 68.5 (C-4),
61.5 (C-6), 25.9 (C-2), 20.7, 20.7, 20.7, 20.5 (CH3COO).
Anal. Calcd for C14H19IO9 (458.192): C, 36.69; H, 4.18.
Found: C, 36.89; H, 4.28.
Compound 7: syrup; [a]D = À15.0 (c 1.0, CHCl3); 1H
NMR (CDCl3): d 6.40 (d, 1H, J = 1.4 Hz, H-1), 5.46 (dd,
1H, J = 9.1, 9.8 Hz, H-4), 4.59 (dd, 1H, J = 4.4, 9.1 Hz,
H-3), 4.53 (dd, 1H, J = 1.4, 4.4 Hz, H-2), 4.24 (dd, 1H,
J = 4.6, 12.4 Hz, H-6a), 4.15 (dd, 1H, J = 2.4, 12.4 Hz,

D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
3373
NMR (CDCl3): d 170.7, 170.7, 170.4, 169.5 (CH3CO),
140.5 (C-5chol), 122.1 (C-6chol), 99.3 (C-1), 79.9 (C-3chol),
72.3 (C-3), 71.5 (C-5), 69.1 (C-4), 62.5 (C-6), 56.8 (C-
14chol), 56.2 (C-17chol), 55.4 (C-2), 50.2 (C-9chol), 42.3 (C-
13chol), 40.1 (C-12chol), 39.8 (C-24chol), 39.5 (C-4chol), 37.1
(C-1chol), 36.6 (C-10chol), 36.2 (C-22chol), 35.8 (C-20chol),
31.9 (C-7chol), 31.8 (C-8chol), 28.2 (C-2chol), 28.0 (C-16chol),
28.0 (C-25chol), 24.3 (C-15chol), 23.8 (C-23chol), 22.3 (C-
27chol), 22.8 (C-26chol), 22.6 (CH3CON), 21.1 (C-11chol),
20.8, 20.8, 20.7 (CH3COO), 19.4 (C-19chol), 18.8 (C-21chol),
11.9 (C-18chol). Anal. Calcd for C41H65NO9 (715.937): C,
68.78; H, 9.15; N, 1.96. Found: C, 68.72; H, 9.15; N, 1.93.
C10H21)2(OCH2CH2)3), 68.7 (C-4), 62.2 (C-6), 53.8
(C-2), 31.8, 29.5, 29.4, 29.3, 26.1, 22.3 (CH2 alkyl chains),
22.9 (CH3CON), 20.6, 20.5, 20.5 (CH3COO), 14.0 (CH3
alkyl chains). Anal. Calcd for C45H83NO14 (862.121): C,
62.69; H, 9.70; N, 1.62. Found: C, 62.41; H, 9.61; N,
1.40.
4.9. Pent-4-enyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
L-glucopyranoside 12
A solution of donor 8 (4.10 g, 9.30 mmol) and pent-4-en-1-
ol (1.45 mL, 14.04 mmol, 1.51 equiv) in CH2Cl2 (10 mL)
was cooled to 10 ꢁC before the dropwise addition of a solu-
tion of PPh3 (3.15 g, 12.00 mmol) in CH2Cl2 (8 mL). The
mixture was stirred overnight at room temperature, con-
centrated under diminished pressure, and then purified on
a short column of silica-gel, using first EtOAc, then 4:1
EtOAc–EtOH as the eluents. The salt was a yellow amor-
4.8. 10-Undecyloxymethyl-3,6,9,12-tetraoxatricosyl 2-acet-
amido-3,4,6-tri-O-acetyl-2-deoxy-b-L-glucopyranoside 11
A solution of donor 8 (0.267 g, 0.605 mmol) and 10-unde-
cyloxymethyl-3,6,9,12-tetraoxatricosanol 1025 (0.311 g,
0.584 mmol) in CH2Cl2 (10 mL) was cooled to 10 ꢁC before
the addition of PPh3 (0.174 g, 0.665 mmol). The mixture
was stirred for 16 h at room temperature before further
addition of donor 8 (0.040 g, 0.091 mmol) and PPh3
(0.025 g, 0.095 mmol) at 10 ꢁC and subsequent stirring at
room temperature for 16 h. After concentration, the resi-
due was purified by column chromatography using first
EtOAc, then 2:1 EtOAc–EtOH as the eluents to isolate
the aminophosphonium salt as a yellow amorphous solid.
1H NMR (CDCl3): d 7.87–7.41 (m, 15H, 3C6H5), 5.86
(dd, 1H, J = 9.5, 9.3 Hz, H-3), 5.70 (d, 1H, J = 8.1 Hz,
H-1), 4.79 (dd, 1H, J = 9.3, 9.7 Hz, H-4), 4.23 (dd, 1H,
J = 4.9, 12.5 Hz, H-6a), 4.00 (dd, 1H, J = 1.8, 12.5 Hz,
H-6b), 3.95 (ddd, J = 9.7, 4.9, 1.8 Hz, 1H, H-5), 3.70–
1
phous solid. Rf 0.50–0.65 (4:1 EtOAc–EtOH); H NMR
(CDCl3): d 7.98–7.47 (m, 15H, 3C6H5), 5.88 (dd, 1H,
J = 9.6, 9.2 Hz, H-3), 5.69 (m, CH@), 5.68 (d, 1H,
J = 8.0 Hz, H-1), 4.98–4.89 (m, 2H, CH2@), 4.81 (dd,
1H, J = 9.2, 9.9 Hz, H-4), 4.27 (dd, 1H, J = 5.2, 12.2 Hz,
H-6a), 4.00 (dd, 1H, J = 1.8, 12.2 Hz, H-6b), 3.95 (ddd,
1H, J = 9.9, 5.2, 1.8 Hz, H-5), 3.76 (m, 1H, 1/2OCH2),
3.51 (m, 1H, 1/2OCH2), 3.02 (ddd, 1H, J = 8.0, 9.6, 21.3,
H-2), 2.01, 1.98 (2s, 6H, 2CH3COO), 2.05–1.80 (m, 2H,
CH2CH@CH2), 1.58 (s, 3H, CH3COO), 1.40–1.05 (m,
2H, OCH2CH2).
The latter was dissolved in the minimum amount of EtOH
and then applied at the top of a column of Dowex 2X8
[OHÀ]. After elution with EtOH and concentration, the
residue was treated overnight by a catalytic amount of
MeONa in MeOH (25 mL). After evaporation, water
(50 mL) was added to the mixture, which was acidified to
pH 4 with 3 M HCl and extracted with CH2Cl2
(5 · 10 mL). The aqueous layer was neutralized with solid
NaHCO3 and concentrated. The residue was co-evaporated
twice from EtOH and acetylated overnight in a 3:2 pyri-
dine–Ac2O mixture (50 mL). The solution was concen-
trated and the residue was purified by column
chromatography (EtOAc, then 6:1 EtOAc–EtOH). Glyco-
side 12 was obtained as a white solid (2.75 g, 71%). Mp
120–122 ꢁC (EtOH); [a]D = +15.3 (c 1.0, CHCl3); 1H
NMR (CDCl3): d 5.80 (m, 1H, CH@), 5.71 (d, 1H,
J = 8.7 Hz, NH), 5.31 (dd, 1H, J = 10.4, 9.4 Hz, H-3),
5.06 (dd, 1H, J = 9.4, 9.8 Hz, H-4), 5.04–4.94 (m, 2H,
@CH2), 4.66 (d, 1H, J = 8.3 Hz, H-1), 4.26 (dd, 1H,
J = 4.7, 12.2 Hz, H-6a), 4.12 (dd, 1H, J = 2.4, 12.2, H-
6b), 3.86 (ddd, 1H, J = 6.7, 6.7, 9.6 Hz, 1/2OCH2), 3.83
(ddd, 1H, J = 8.3, 10.4, 8.7 Hz, H-2), 3.71 (ddd, 1H,
J = 9.8, 4.7, 2.4 Hz, H-5), 3.49 (ddd, 1H, J = 6.7, 6.7,
9.6 Hz, 1/2OCH2), 2.15–2.08 (m, 2H, CH2–CH@CH2),
2.07, 2.02, 2.01, 1.94 (4s, 12H, 4CH3CO), 1.70–1.62 (m,
2H, OCH2CH2); 13C NMR (CDCl3): d 170.7, 170.7,
170.4, 169.4 (CH3CO), 137.9 (CH@), 115.0 (@CH2),
100.7 (C-1), 72.5 (C-3), 71.6 (C-5), 69.1 (OCH2), 69.0 (C-
4), 62.3 (C-6), 54.6 (C-2), 28.9, 28.6 (OCH2CH2CH2),
23.2 (CH3CON), 20.7, 20.7, 20.6 (CH3COO). Anal. Calcd
for C19H29NO9 (415.429): C, 54.94; H, 7.04; N, 3.37.
Found: C, 55.30; H, 7.05; N, 3.32.
3.00
(m,
22H,
H-2,
OCH(CH2OCH2C10H21)2-
(OCH2CH2)3), 2.00, 1.96 (2s, 6H, 2CH3COO), 1.60–1.40
(m, 7H, CH3COO, 2OCH2CH2C9H19), 1.35–1.20 (m,
32H, 16CH2 alkyl chains), 0.86 (t, 6H, J = 6.4 Hz, 2CH3
alkyl chains).
The latter was dissolved in the minimum amount of EtOH
and was applied at the top of a column of Dowex 2X8
[OHÀ]. After elution with EtOH and concentration, the
residue was treated overnight by a catalytic amount of
MeONa in MeOH (5 mL), then concentrated and acetyl-
ated overnight in a 2:1 pyridine–Ac2O mixture (15 mL).
After evaporation under diminished pressure, the mixture
was purified by column chromatography (EtOAc, then
4:1 EtOAc–EtOH); a second purification was necessary
for the elimination of remaining traces of PPh3O (7:4
Me2CO–petroleum ether). Pure product 11 was obtained
as a waxy material (0.255 g, 51%). Rf 0.58 (3:2 Me2CO–
1
petroleum ether); [a]D = +14.5 (c 1.0, CHCl3); H NMR
(CDCl3): d 6.75 (d, 1H, J = 9.3 Hz, NH), 5.15–5.05 (m,
2H, H-3, H-4), 4.80 (d, 1H, J = 8.6 Hz, H-1), 4.26 (dd,
1H, J = 4.4, 12.2 Hz, H-6a), 4.16 (dd, 1H, J = 1.9,
12.1 Hz, H-6b), 4.16–4.08 (m, 1H, H-5), 3.94–3.42 (m,
22H, H-2, OCH(CH2OCH2C10H21)2(OCH2CH2)3), 2.08,
2.01, 2.00, 1.96 (4s, 12H, 4CH3CO), 1.60–1.40 (m, 4H,
2OCH2CH2C9H19), 1.35–1.20 (m, 32H, 16CH2 alkyl
chains), 0.86 (t, 6H, J = 6.5 Hz, 2CH3 alkyl chains). 13C
NMR (CDCl3): d 170.7, 170.7, 170.4, 169.5 (CH3CO),
101.7 (C-1), 78.3 (HC(CH2OC11H23)2), 73.3 (C-3), 71.6
(C-5), 71.5, 71.4, 70.6, 69.7, 68.6 (C(CH2OCH2-

3374
D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
4.9.1. Pent-4-enyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-
D-glucopyranoside 12-D. Obtained in 71% yield as de-
scribed above from 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-a-D-
mannopyranosyl azide (8-D). Product 12-D was a white
solid; mp 121–123 ꢁC (EtOH) [lit.36 mp 122–124 ꢁC
(EtOH)]; [a]D = À15.0 (c 1.0, CHCl3) {lit.37 [a]D = À15.0
(c 1.1, CHCl3)}.
sodium. After concentration, the product was acetylated
overnight in a 2:3 Ac2O–pyridine mixture (30 mL). The
solution was concentrated under diminished pressure and
the residue was co-evaporated from toluene (2 · 15 mL).
The product was purified by column chromatography
(1:1 EtOAc–petroleum ether) and recrystallized from abso-
lute EtOH (2.41 g, 92%). Mp 150 ꢁC (EtOH); [a]D = +1.9
1
(c 1.6, CHCl3); Rf 0.70 (EtOAc–petroleum ether 1:1); H
4.10. Pent-4-enyl N-acetyl-3,4,6-tri-O-acetyl-N-tert-but-
oxycarbonylamino-2-deoxy-b-L-glucopyranoside 13
NMR (CDCl3): d 5.76 (m, 1H, CH@), 5.25 (dd, 1H,
J = 11.1, 8.0 Hz, H-3), 5.04–4.91 (m, 2H, CH2@), 4.90
(dd, 1H, J = 8.0, 9.9 Hz, H-4), 4.73–4.56 (m, 2H, H-1,
NH), 4.24 (dd, 1H, J = 4.9, 12.2 Hz, H-6a), 4.08 (dd, 1H,
J = 2.3, 12.2 Hz, H-6b), 3.86 (ddd, 1H, J = 9.6, 6.3,
6.3 Hz, 1/2OCH2), 3.65 (ddd, 1H, J = 9.9, 4.9, 2.3 Hz, H-
5), 3.48 (ddd, 1H, J = 6.6, 11.1, 8.6 Hz, H-2), 3.47 (ddd,
1H, J = 9.6, 6.3, 6.3 Hz, 1/2OCH2), 2.15–2.05 (m, 2H,
CH2CH@CH2), 2.04, 2.00, 1.98 (3s, 9H, 3CH3COO),
1.73–1.60 (m, 2H, OCH2CH2), 1.39 (s, 9H, (CH3)3C); 13C
NMR (CDCl3): d 170.7, 170.5, 169.5 (CH3COO), 155.1
(NHCOO), 137.9 (CH@), 115.0 (CH2@), 101.2 (C-1),
79.9 (C(CH3)3), 72.4 (C-3), 71.7 (C-5), 69.3 (OCH2), 69.0
(C-4), 62.3 (C-6), 55.9 (C-2), 29.9, 28.7 (OCH2CH2CH2),
28.3 (C(CH3)3), 20.7, 20.7, 20.6 (CH3COO). Anal. Calcd
for C22H35NO10 (473.507): C, 55.80; H, 7.45; N, 2.96.
Found: C, 56.08; H, 7.31; N, 2.70.
A mixture of glycoside 12 (2.54 g, 6.11 mmol), Boc2O
(4.00 g, 18.33 mmol), and DMAP (0.225 g, 1.84 mmol) in
dry THF (20 mL) was refluxed for 5 h under argon. After
concentration, the residue was purified by column chroma-
tography using first 1:2 EtOAc–petroleum ether, then 1:1
EtOAc–petroleum ether as the eluents. Pure compound
13 was obtained as an oily material (2.93 g, 93%).
[a]D = +20.3 (c 1.0, CHCl3); Rf 0.83 (1:1 EtOAc–petroleum
ether). 1H and 13C NMR spectra showed two rotamers
1
around the amide bond leading to a broad H NMR spec-
trum. 1H NMR (CDCl3): d 5.82–5.66 (m, 2H, H-3, CH@),
5.32 (d, 0.4H, J = 8.0 Hz, H-1min), 5.13–4.93 (m, 3.6H,
H-1maj, H-4, CH2@), 4.87 (dd, 0.6H, J = 8.0, 10.4 Hz,
H-2maj), 4.35–4.07 (m, 2.4H, H-2min, H-6a, H-6b), 3.85
(ddd, 1H, J = 10.4, 6.3, 6.3 Hz, 1/2OCH2), 3.72–3.62 (m,
1H, H-5), 3.45 (ddd, 1H, J = 10.4, 6.3, 6.3 Hz, 1/
2OCH2), 2.41 (s, 1.2H, CH3CON), 2.34 (s, 1.8H,
CH3CON), 2.25–2.05 (m, 2H, CH2–CH@CH2), 2.08 (s,
3H, CH3COO), 2.04 (s, 1.2H, CH3COO minor rotamer),
2.01 (s, 3H, CH3COO), 1.98 (s, 1.8H, CH3COO major rot-
amer), 1.75–1.60 (m, 2H, OCH2CH2), 1.58 (s, 3.6H,
(CH3)3C minor rotamer), 1.51 (s, 5.4H, (CH3)3C major rot-
amer); 13C NMR, minor rotamer (CDCl3): d 172.9
(CH3CON), 170.7, 170.6, 169.6 (CH3COO), 152.0
(NCOO), 137.8 (CH@), 115.0 (CH2@), 100.2 (C-1), 84.5
(C(CH3)3), 71.6, 71.2 (C-3, C-5), 69.6 (C-4), 69.1 (OCH2),
62.2 (C-6), 56.7 (C-2), 29.8, 28.6 (OCH2CH2CH2), 28.0
(C(CH3)3), 26.8 (CH3CON), 20.8, 20.7, 20.6 (CH3COO).
13C NMR, major rotamer (CDCl3): d 174.0 (CH3CON),
170.7, 170.6, 169.6 (CH3COO), 153.4 (NCOO), 137.8
(CH@), 115.0 (CH2@), 99.5 (C-1), 83.9 (C(CH3)3), 71.4,
70.6 (C-3, C-5), 69.6 (C-4), 69.2 (OCH2), 62.2 (C-6), 61.6
(C-2), 29.8, 28.6 (OCH2CH2CH2), 27.9 (C(CH3)3), 27.2
(CH3CON), 20.8, 20.7, 20.6 (CH3COO). Anal. Calcd for
C24H37NO11 (515.543): C, 55.91; H, 7.43; N, 2.72. Found:
C, 55.64; H, 7.43; N, 2.54.
4.11.1. Pent-4-enyl 3,4,6-tri-O-acetyl-2-butoxycarbonyl-
amino-2-deoxy-b-D-glucopyranoside 14-D. Obtained in
88% as described above from 13-D. Mp 150 ꢁC (EtOH);
[a]D = À2.5 (c 1.5, CHCl3); Rf 0.70 (1:1 EtOAc–petroleum
1
ether); H and 13C NMR spectra were identical with those
of compound 14. Anal. Calcd for C22H35NO10 (473.507):
C, 55.80; H, 7.45; N, 2.96. Found: C, 55.32; H, 7.50; N,
2.79.
4.12. Pent-4-enyl 3,4,6-tri-O-acetyl-2-amino-2-deoxy-b-L-
glucopyranoside 15
A solution of glycoside 14 (2.36 g, 4.98 mmol) and trifluo-
roacetic acid (2 mL) in CH2Cl2 (5 mL) was stirred over-
night at room temperature. After concentration and co-
evaporation from toluene (2 · 10 mL), the residue was dis-
solved in CH2Cl2 (50 mL). Then, the organic solution was
washed with satd aq NaHCO3 (10 mL) and dried over
Na2SO4 before evaporation to afford compound 15 in pure
form as an amorphous solid (1.86 g, 100%). [a]D = À5.1 (c
1.0, CHCl3); 1H NMR (CDCl3): d 5.82 (dddd, 1H, J = 6.6,
6.6, 10.3, 16.9 Hz, CH@), 5.08–4.93 (m, 4H, H-3, H-4,
CH2@), 4.30 (dd, 1H, J = 4.8, 12.2 Hz, H-6a), 4.24 (d,
1H, J = 8.0 Hz, H-1), 4.11 (dd, 1H, J = 2.3, 12.2 Hz, H-
6b), 3.94 (ddd, 1H, J = 6.3, 6.3, 9.6 Hz, 1/2OCH2), 3.68
(ddd, 1H, J = 9.2, 4.8, 2.3 Hz, H-5), 3.54 (ddd, 1H,
J = 6.3, 6.3, 9.6 Hz, 1/2OCH2), 2.94 (dd, 1H, J = 8.0,
9.9 Hz, H-2), 2.20–2.09 (m, 2H, CH2CH@CH2), 2.09,
2.08, 2.03 (3s, 9H, 3CH3COO), 1.81–1.67 (m, 2H,
OCH2CH2), 1.50–1.37 (m, 2H, NH2); 13C NMR (CDCl3):
d 170.7, 170.6, 169.7 (CH3COO), 137.8 (CH@), 115.1
(CH2@), 104.1 (C-1), 75.4 (C-3), 71.8 (C-5), 69.6 (OCH2),
69.0 (C-4), 62.3 (C-6), 55.9 (C-2), 30.1, 28.7
(OCH2CH2CH2), 20.8, 20.7, 20.7 (CH3COO). Anal. Calcd
for C17H27NO8 (373.393): C, 54.68; H, 7.29; N, 3.75.
Found: C, 54.93; H, 7.38; N, 3.69.
4.10.1.
Pent-4-enyl
N-acetyl-3,4,6-tri-O-acetyl-N-tert-
13-
butoxycarbonylamino-2-deoxy-b-D-glucopyranoside
D. Obtained in 95% as described above from the acetam-
ido derivative 12-D. [a]D = À20.2 (c 1.0, CHCl3); Rf 0.83
1
(1:1 EtOAc–petroleum ether); H and 13C NMR spectra
were identical with those of compound 13. Anal. Calcd
for C24H37NO11 (515.543): C, 55.91; H, 7.43; N, 2.72.
Found: C, 55.83; H, 7.24; N, 2.71.
4.11. Pent-4-enyl 3,4,6-tri-O-acetyl-2-tert-butoxycarbonyl-
amino-2-deoxy-b-L-glucopyranoside 14
Compound 12 (2.85 g, 5.53 mmol) in MeOH (50 mL) was
stirred for 6 h in the presence of a catalytic amount of

D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
3375
4.12.1. Pent-4-enyl 3,4,6-tri-O-acetyl-2-amino-2-deoxy-b-D-
glucopyranoside 15-D. Obtained in 95% as described
above from 14-D. [a]D = +4.8 (c 1.0, CHCl3); Rf 0.30–0.35
(CH2Cl2–MeOH, 1:1), {lit.38 [a]D = +5.4 (c 1.1, CHCl3)}.
2.04, 1.96 (4s, 12H, 4CH3CO), 1.25 (t, 3H, J = 7.4 Hz,
SCH2CH3); 13C NMR (CDCl3): d 170.9, 170.8, 170.4,
169.4 (CH3CO), 84.3 (C-1), 75.7 (C-3), 73.9 (C-5), 68.7
(C-4), 62.5 (C-6), 53.2 (C-2), 24.2 (SCH2CH3), 23.2
(CH3CON), 20.8, 20.7, 20.6 (CH3COO), 14.9 (SCH2CH3).
Anal. Calcd for C16H25NO8S (391.431): C, 49.09; H, 6.44;
N, 3.58. Found: C, 48.78; H, 6.42; N, 3.50.
4.13. Pent-4-enyl 3,4,6-tri-O-acetyl-2-allyloxycarbonyl-
amino-2-deoxy-b-L-glucopyranoside 16
Pentenyl glycoside 15 (1.86 g, 4.98 mmol) was dissolved in
CHCl3 (40 mL) before subsequent additions of a solution
of NaHCO3 (0.836 g, 9.96 mmol) in H2O (20 mL) and allyl
chloroformate (0.637 mL, 7.20 mmol). The mixture was
stirred for 6 h; the aqueous phase was extracted with
CHCl3 (2 · 20 mL) and the combined organic extracts
washed once with water, dried, and concentrated under
diminished pressure. The residue was purified by column
chromatography (1:1 EtOAc–petroleum ether). Product
16 was obtained as a solid and recrystallized from absolute
EtOH (2.05 g, 90%). Mp 94–95 ꢁC (EtOH); [a]D = À1.0 (c
5.0, CHCl3); Rf 0.60 (EtOAc–petroleum ether 1:1); 1H
NMR (CDCl3): d 6.00–5.69 (m, 2H, 2CH@), 5.33–4.94
(m, 6H, 2CH2@, H-3, H-4), 4.86 (d, 1H, J = 6.5 Hz,
NH), 4.64–4.52 (m, 3H, H-1, allyl CH2), 4.24 (dd, 1H,
J = 4.7, 12.2 Hz, H-6a), 4.12 (dd, 1H, J = 2.1, 12.2 Hz,
H-6b), 3.90 (ddd, 1H, J = 6.2, 6.2, 9.4 Hz, pent. 1/
2OCH2), 3.69 (ddd, 1H, J = 9.3, 4.7, 2.1 Hz, H-5), 3.65–
3.44 (m, 2H, H-4, pent. 1/2OCH2), 2.15–2.05 (m, 2H, pent.
CH2CH@CH2), 2.09, 2.04, 2.03 (3s, 9H, 3CH3COO), 1.75–
1.60 (m, 2H, OCH2CH2); 13C NMR (CDCl3): d 170.7,
170.7, 169.5 (CH3COO), 155.7 (NHCOO), 137.9 (pent.
CH@), 132.7 (allyl CH@), 117.7 (allyl CH2@), 115.0 (pent.
CH2@), 101.2 (C-1), 72.3 (C-3), 71.7 (C-5), 69.4 (pent.
OCH2), 68.9 (C-4), 65.7 (allyl OCH2), 62.3 (C-6), 56.1
(C-2), 29.9, 28.6 (OCH2CH2CH2), 20.8, 20.7, 20.7
(CH3COO). Anal. Calcd for C21H31NO10 (457.465): C,
55.13; H, 6.83; N, 3.06. Found: C, 54.89; H, 6.82; N, 2.78.
4.15. Ethyl N-acetyl-3,4,6-tri-O-acetyl-2-tert-butoxycar-
bonylamino-2-deoxy-1-thio-b-L-glucopyranoside 18
A mixture of thioglycoside 17 (1.076 g, 2.75 mmol), Boc2O
(1.44 g, 6.87 mmol), and DMAP (0.030 g) in dry THF
(6 mL) was refluxed for 3 h under argon. Concentration
of the solution gave a residue, which was purified by column
chromatography (1:1 EtOAc–petroleum ether) to afford
pure derivative 18 as an oil (1.22 g, 90%). [a]D = +5.7 (c
1.0, CHCl3); Rf 0.80 (EtOAc–petroleum ether 1:1). 1H
and 13C NMR spectra showed two rotamers around the
1
amide bond. Major rotamer, H NMR (CDCl3): d 5.82
(dd, 1H, J = 9.9, 9.0 Hz, H-3), 5.53 (d, 1H, J = 10.1 Hz,
H-1), 5.07 (dd, 1H, J = 9.0, 9.9 Hz, H-4), 4.27 (dd, 1H,
J = 10.1, 9.9 Hz, H-2), 4.29–4.05 (m, 2H, H-6a, H-6b),
3.78 (ddd, 1H, J = 9.9, 5.1, 2.2 Hz, H-5), 2.71–2.57 (m,
2H, SCH2), 2.36 (s, 3H, CH3CON), 2.09–1.96 (m, 9H,
3CH3COO), 1.54 (s, 9H, (CH3)3C), 1.26 (t, 3H,
J = 7.4 Hz, SCH2CH3); 13C NMR (CDCl3): d 173.0
(CH3CON), 170.4, 170.0, 169.2 (CH3COO), 151.6 (NCOO),
84.6 (C(CH3)3), 83.2 (C-1), 75.8 (C-3), 71.8 (C-5), 69.5 (C-
4), 62.3 (C-6), 55.6 (C-2), 28.0 (C(CH3)3), 26.7 (CH3CON),
24.1 (SCH2CH3), 20.6, 20.5, 20.4 (CH3COO), 15.0
(SCH2CH3). Minor rotamer, 1H NMR (CDCl3): d 5.72
(dd, 1H, J = 10.2, 9.0 Hz, H-3), 5.27 (d, 1H, J = 10.2 Hz,
H-1), 5.11 (dd, 1H, J = 9.0, 9.9 Hz, H-4), 4.94 (dd, 1H,
J = 10.2, 10.2 Hz, H-2), 4.29–4.05 (m, 2H, H-6a, H-6b),
3.71 (ddd, 1H, J = 9.9, 5.1, 2.1 Hz, H-5), 2.71–2.62 (m,
2H, SCH2CH3), 2.44 (s, 3H, CH3CON), 2.09–1.96 (m,
9H, 3CH3COO), 1.59 (s, 9H, (CH3)3C), 1.26 (t, 3H,
J = 7.4 Hz, SCH2CH3). 13C NMR (CDCl3): d 173.6
(CH3CON), 170.0, 169.8, 169.5 (CH3COO), 153.0 (NCOO),
84.2 (C(CH3)3), 82.6 (C-1), 75.5 (C-3), 71.3 (C-5), 69.5 (C-
4), 62.4 (C-6), 60.4 (C-2), 27.8 (C(CH3)3), 26.7 (CH3CON),
24.9 (SCH2CH3), 20.6, 20.5, 20.4 (CH3COO), 15.1
(SCH2CH3). Anal. Calcd for C21H33NO10S (491.545): C,
51.31; H, 6.77; N, 2.85. Found: C, 51.39; H, 6.80; N, 2.84.
4.13.1. Pent-4-enyl 3,4,6-tri-O-acetyl-2-allyloxycarbonyl-
amino-2-deoxy-b-D-glucopyranoside 16-D. Obtained in
95% as described above from 15-D. Mp 95–96 ꢁC (EtOH);
[a]D = +1.2 (c 1.0, CHCl3) {lit.39 [a]D = +0.4 (c 1.1,
CHCl3)}; Rf 0.60 (1:1 EtOAc–petroleum ether).
4.14. Ethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-
L-glucopyranoside 17
Ethanethiol (3.15 mL, 42.5 mmol) was added at 0 ꢁC to a
solution of donor 8 (3.70 g, 8.40 mmol) in CH2Cl2
(25 mL). A solution of PPh3 (2.42 g, 1.1 equiv) in CH2Cl2
(10 mL) was then added dropwise and the mixture stirred
overnight at room temperature, before evaporation. The
aminophosphonium salt was transformed as described
above for compound 12 and crude product 17 was purified
by column chromatography (EtOAc). Glycoside 17 was
obtained as a white solid (1.41 g, 43%). Mp 190–192 ꢁC
4.15.1. Ethyl N-acetyl-3,4,6-tri-O-acetyl-2-tert-butoxy-
18-
carbonylamino-2-deoxy-1-thio-b-D-glucopyranoside
D. Obtained in 95% yield as described for 17 from ethyl
2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-b-D-gluco-
pyranoside 17-D.40 Compound 18-D was obtained as an
oil. [a]D = À6.2 (c 1.0, CHCl3); Rf 0.80 (EtOAc–petroleum
1
ether 1:1); H and 13C NMR spectra were identical with
those of compound 18. Anal. Calcd for C21H33NO10S
(491.545): C, 51.31; H, 6.77; N, 2.85. Found: C, 51.27; H,
6.63; N, 2.97.
1
(EtOH); [a]D = +42.8 (c 1.0, CHCl3); H NMR (CDCl3):
d 5.58 (d, 1H, J = 9.5 Hz, NH), 5.19 (dd, 1H, J = 9.9,
8.9 Hz, H-3), 5.10 (dd, 1H, J = 8.9, 9.9 Hz, H-4), 4.60 (d,
1H, J = 10.3 Hz, H-1), 4.25 (dd, 1H, J = 4.9, 12.4 Hz, H-
6a), 4.13 (dd, 1H, J = 2.4, 12.4 Hz, H-6b), 4.10 (ddd, 1H,
J = 10.3, 9.9, 9.5 Hz, H-2), 3.71 (ddd, 1H, J = 9.9, 4.9,
2.4 Hz, H-5), 2.79–2.67 (m, 2H, SCH2CH3), 2.08, 2.04,
4.16. Ethyl 3,4,6-tri-O-acetyl-2-tert-butoxycarbonylamino-
2-deoxy-1-thio-b-L-glucopyranoside 19
Compound 18 (1.20 g, 2.44 mmol) in MeOH (15 mL) was
stirred for 6 h in the presence of a catalytic amount of

3376
D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
sodium. After concentration, the product was acetylated
overnight in a 3:4 Ac2O–pyridine mixture (30 mL). The
solution was concentrated under diminished pressure and
the residue co-evaporated from toluene (2 · 15 mL). The
product was purified by column chromatography (2:1
EtOAc–petroleum ether), recrystallized from absolute
EtOH, and obtained as a white solid (0.980 g, 90%). Mp
149–150 ꢁC (EtOH); [a]D = +22.9 (c 1.6, CHCl3); Rf 0.80
purification in the next step. Rf 0.30 (CH2Cl2–MeOH
20:1); [a]D = À21.7 (c 1.0, CHCl3).
4.18. Ethyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-
deoxy-1-thio-b-L-glucopyranoside 21
Compound 20 (0.600 g, 1.72 mmol) was dissolved in CHCl3
(15 mL) before subsequent additions of a solution of NaH-
CO3 (0.288 g, 3.44 mmol) in H2O (15 mL) and allyl chloro-
fomate (0.218 mL, 2.04 mmol). The mixture was stirred for
4 h; the aqueous phase was extracted with CHCl3
(2 · 15 mL) and the combined organic extracts dried and
concentrated under reduced pressure. The residue was puri-
fied by column chromatography (1:1 EtOAc–petroleum
ether). Product 21 was obtained as a white solid (0.706 g,
95%). Mp 129–131 ꢁC (EtOH); [a]D = +18.5 (c 1.0, CHCl3);
Rf 0.66 (1:1 EtOAc–petroleum ether); 1H NMR (CDCl3): d
5.90 (m, 1H, CH@), 5.34–5.19 (m, 3H, CH2@, H-3), 5.07
(dd, 1H, J = 9.5, 9.6 Hz, H-4), 4.88 (d, 1H, J = 8.2 Hz,
NH), 4.65–4.56 (m, 3H, H-1, allyl CH2), 4.26 (dd, 1H,
J = 5.0, 12.3 Hz, H-6a), 4.13 (dd, 1H, J = 2.4, 12.3 Hz, H-
6b), 3.76 (ddd, 1H, J = 10.4, 10.0, 8.2 Hz, H-2), 3.70
(ddd, 1H, J = 9.6, 5.0, 2.4 Hz, H-5), 2.74 (q, 2H,
1
(EtOAc–petroleum ether 2:1); H NMR (CD3COCD3): d
6.15 (d, 1H, J = 9.5 Hz, NH), 5.21 (dd, 1H, J = 10.0,
9.4 Hz, H-3), 4.98 (dd, 1H, J = 9.4, 10.0 Hz, H-4), 4.84
(dd, 1H, J = 10.4 Hz, H-1), 4.24 (d, 1H, J = 5.3, 12.2 Hz,
H-6a), 4.09 (dd, 1H, J = 2.4, 12.2 Hz, H-6b), 3.81 (ddd,
1H, J = 10.0, 5.3, 2.4 Hz, H-5), 3.76 (ddd, 1H, J = 10.4,
10.0, 9.5 Hz, H-2), 2.77–2.67 (m, 2H, SCH2CH3), 2.02,
1.99, 1.95 (3s, 9H, 3CH3COO), 1.40 (s, 9H, (CH3)3C),
1.25 (t, 3H, J = 7.4 Hz, SCH2CH3); 13C NMR (CDCl3):
d 170.7, 170.6, 169.4 (CH3COO), 155.0 (NHCOO), 84.6
(C-1), 80.0 (C(CH3)3), 75.8 (C-3), 73.8 (C-5), 68.8 (C-4),
62.5 (C-6), 54.6 (C-2), 28.3 (C(CH3)3), 24.2 (SCH2CH3),
20.7, 20.7, 20.6 (CH3COO), 14.9 (SCH2CH3). Anal. Calcd
for C19H31NO9S (449.509): C, 50.76; H, 6.95; N, 3.12.
Found: C, 50.36; H, 6.89; N, 3.00.
J = 7.5 Hz, SCH2CH3), 2.08, 2.04, 2.03 (3s,
9 H,
3CH3COO), 1.28 (t, 3H, J = 7.5 Hz, CH3CH2S); 13C
NMR (CDCl3): d 170.7, 170.7, 169.5 (CH3COO), 155.7
(NHCOO), 132.7 (CH@), 117.5 (CH2@), 84.5 (C-1), 75.7
(C-3), 73.7 (C-5), 68.8 (C-4), 65.8 (allyl CH2), 62.5 (C-6),
55.0 (C-2), 24.3 (SCH2CH3), 20.7, 20.7, 20.6 (CH3COO),
14.9 (SCH2CH3). Anal. Calcd for C18H27NO9S (433.467):
C, 49.87; H, 6.28; N, 3.23. Found: C, 49.88; H, 6.03; N, 3.21.
4.16.1. Ethyl 3,4,6-tri-O-acetyl-2-tert-butoxycarbonylamino-
2-deoxy-1-thio-b-D-glucopyranoside 19-D. Obtained in
93% yield from 18-D as described for 19. Compound
19-D was a crystalline solid. Mp 151–152 ꢁC (EtOH);
[a]D = À23.0 (c 1.0, CHCl3); Rf 0.80 (EtOAc–petroleum
1
ether 1:1); H and 13C NMR spectra were identical with
those of compound 19. Anal. Calcd for C19H31NO9S
(449.509): C, 50.76; H, 6.95; N, 3.12. Found: C, 50.36; H,
6.99; N, 3.14.
4.18.1. Ethyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-
deoxy-1-thio-b-D-glucopyranoside 21-D. Obtained in 90%
yield from 20-D as described for 21. Compound 21-D
was recrystallized from absolute EtOH. Product 21 was
obtained in 93% yield. Rf 0.66 (1:1 EtOAc–petroleum
ether); mp 133–134 ꢁC (EtOH); [a]D = À18.0 (c 1.0,
CHCl3). These data are in agreement with our preceding
results.41
4.17. Ethyl 3,4,6-tri-O-acetyl-2-amino-2-deoxy-1-thio-b-L-
glucopyranoside 20
A mixture of glycoside 19 (0.820 g, 1.82 mmol) and trifluo-
roacetic acid (2 mL) in CH2Cl2 (4 mL) was stirred over-
night at room temperature, then concentrated under
diminished pressure, and co-evaporated from toluene
(2 · 15 mL). The residue was diluted in CH2Cl2 (40 mL)
and the organic solution was washed with satd aq NaHCO3
(15 mL), then with water (10 mL) and dried over Na2SO4.
Concentration afforded the amino derivative 20, which was
used without purification in the next step (0.604 g, 95%). Rf
0.30 (CH2Cl2–MeOH, 20:1); [a]D = +22.0 (c 1.0, CHCl3);
1H NMR (CD3Cl3): d 5.08–4.95 (m, 2H, H-3, H-4), 4.37
(d, 1H, J = 10.0 Hz, H-1), 4.27 (d, 1H, J = 5.0, 12.3 Hz,
H-6a), 4.11 (dd, 1H, J = 1.8, 12.3 Hz, H-6b), 3.77–3.64
(m, 1H, H-5), 3.02–2.93 (m, 1H, H-2), 2.75 (q, 2H,
J = 7.4 Hz, SCH2CH3), 2.09, 2.08, 2.03 (3s, 9H,
3CH3COO), 1.33 (t, 3H, J = 7.4 Hz, SCH2CH3); 13C
NMR (CDCl3): d 170.6, 170.6, 169.7 (CH3COO), 87.6
(C-1), 76.6 (C-3), 75.7 (C-5), 68.8 (C-4), 62.5 (C-6), 55.3
(C-2), 24.6 (SCH2CH3), 20.8, 20.7, 20.6 (CH3COO), 15.2
(SCH2CH3).
4.19. 10-Tetradecyloxymethyl-3,6,9,12-tetraoxahexacosyl
3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-b-L-
glucopyranoside 23
Trimethylsilyl trifluoromethanesulfonate (0.092 mL, 0.476
mmol), was added at À20 ꢁC under argon to a mixture of
pentenyl glycoside 16 (0.210 g, 0.459 mmol), 10-tetradecyl-
oxymethyl-3,6,9,12-tetraoxahexacosanol34 22 (0.297 g,
0.482 mmol), N-iodosuccinimide (0.115 g, 0.545 mmol),
˚
and crushed activated 4 A molecular sieves (0.500 g) in
dry alcohol-free CH2Cl2 (5 mL). The mixture was stirred
for 16 h at À20 ꢁC, and then neutralized with Et3N
(0.150 mL), filtered through Celite, and diluted with
CH2Cl2 (50 mL). The organic solution was washed succes-
sively with aq Na2S2O3, aq NaHCO3 (15 mL), then with
water (15 mL). After drying and evaporation under dimin-
ished pressure, the crude product was purified by column
chromatography (3:2 EtOAc–petroleum ether) to afford
compound 23 as an amorphous solid (0.373 g, 82%). Rf
0.60 (3:2 EtOAc–petroleum ether); [a]D = +5.6 (c 1.0,
4.17.1. Ethyl 3,4,6-tri-O-acetyl-2-amino-deoxy-1-thio-b-D-
glucopyranoside 20-D. Obtained in 95% yield from 19-D
as described for 20. Compound 20-D was used without
1
CHCl3). H NMR (CDCl3): d 6.00–5.77 (m, 2H, CH@,

D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
3377
NH), 5.33–5.16 (m, 2H, CH2@), 5.12–5.06 (m, 1H, H-3),
5.05 (dd, 1H, J = 9.2, 9.5 Hz, H-4), 4.79 (d, 1H,
J = 8.3 Hz, H-1), 4.60–4.54 (m, 2H, allyl CH2), 4.28 (dd,
1H, J = 4.6, 12.2 Hz, H-6a), 4.16 (dd, 1H, J = 2.2,
12.2 Hz, H-6b), 3.95–3.40 (m, 23H, H-2, H-5,
CH(CH2OCH2C13H27)2(OCH2CH2)3), 2.09, 2.02, 2.01 (3s,
9H, 3CH3COO), 166–1.50 (m, 4H, 2OCH2CH2C12H25),
1.40–1.20 (m, 44H, 22CH2 alkyl chains), 0.88 (t, 6H,
J = 6.3 Hz, 2CH3 alkyl chains); 13C NMR (CDCl3): d
170.6, 170.5, 170.3 (CH3COO), 156.2 (NHCOO), 133.0
(CH@), 117.1 (CH2@), 101.8 (C-1), 76.6 (CH(CH2-
OC14H29)2), 73.0 (C-3), 71.7 (C-5), 71.6, 71.3, 70.6, 69.9,
68.9 (C(CH2OCH2C13H27)2(OCH2CH2)3), 68.6 (C-4), 65.4
(allyl CH2), 62.2 (C-6), 55.9 (C-2), 31.9, 29.6, 29.5, 29.3,
26.1, 22.6 (CH2 alkyl chains), 20.7, 20.6, 20.5 (CH3COO),
14.1 (CH3 alkyl chains). Anal. Calcd for C53H97NO15
(988.34): C, 64.41; H, 9.89; N, 1.42. Found: C, 64.35; H,
9.78; N, 1.43.
in 74% yield. Mp 60–61 ꢁC; [a]D = +6.5 (c 1.0, CHCl3);
1H and 13C NMR spectra were identical with those of com-
pound 25. Anal. Calcd for C41H73NO12 (772.00): C, 63.78;
H, 9.53; N, 1.82. Found: C, 63.55; H, 9.52; N, 1.79.
4.21. General procedure for the cleavage of the N-allyloxy-
carbonyl group of compounds 23, 25, and 25-D
Tris(dibenzylideneacetone)dipalladium (0.012 g, 0.0126
mmol) and PPh3 (0.032 g, 0.122 mmol) were reacted for
10 min in dry oxygen-free THF (2 mL) under argon. The
solution was added to a solution of N-allyloxycarbonyl
derivative (0.35 mmol) and diethyl malonate (0.60 mL,
3.95 mmol) in dry THF and the mixture was stirred for
16 h under argon. After concentration, the residue was
eluted on a short column of silica-gel to separate the free
amino derivative, which was acetylated in a 2:1 pyridine–
Ac2O mixture (3 mL). The pure peracetylated derivatives
were obtained after concentration and purification of the
residue by column chromatography.
4.20. 1,3-Bis(undecyloxy)prop-2-yl 3,4,6-tri-O-acetyl-2-
allyloxycarbonylamino-2-deoxy-b-L-glucopyranoside 25
4.21.1. 10-Tetradecyloxymethyl-3,6,9,12-tetraoxahexacosyl
2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-b-L-glucopyranoside
26. Compound 26 was prepared from 23 as described
above. The 2-amino intermediate was purified by column
chromatography (1:2 acetone–petroleum ether, Rf 0.54);
then, compound 26 was purified by column chromatogra-
phy (1:10 EtOH–EtOAc) and obtained as an amorphous
solid (77%). Rf 0.63 (1:10 EtOH–EtOAc); [a]D = +13.5 (c
Trimethylsilyl trifluoromethanesulfonate (0.092 mL, 0.502
mmol), was added at À20 ꢁC under argon to a mixture of
thioethyl glycoside 21 (0.217 g, 0.50 mmol), 1,3-bis(unde-
cyloxy)-propan-2-ol25 24 (0.200 g, 0.50 mmol), N-iodosuc-
˚
cinimide (0.124 g, 0.588 mmol), and crushed activated 4 A
molecular sieves (0.500 g) in dry alcohol-free CH2Cl2
(5 mL). The mixture was stirred for 16 h at À20 ꢁC, then
neutralized with Et3N (0.150 mL), filtered through Celite,
and diluted with CH2Cl2 (50 mL). The organic solution
was washed successively with aq Na2S2O3, aq NaHCO3
(15 mL), then with water (15 mL). After drying and evapo-
ration under diminished pressure, the crude product was
purified by column chromatography (2:3 EtOAc–petro-
leum ether) to afford compound 25 as a solid (0.293 g,
76%). Mp 60–61 ꢁC; Rf 0.75 (2:3 EtOAc–petroleum ether);
1.0, CHCl3); 1H NMR (CDCl3):
d 6.72 (d, 1H,
J = 9.4 Hz, NH), 5.14–5.04 (m, 2H, H-3, H-4), 4.81 (dd,
1H, J = 8.5 Hz, H-1), 4.27 (dd, 1H, J = 4.5, 12.2 Hz, H-
6a), 4.16 (m, 1H, OCH(CH2OC14H29)2), 4.13 (dd, 1H,
J = 2.0, 12.2 Hz, H-6b), 3.88–3.40 (m, 22H, H-2, H-5,
OCH(CH2OCH2C13H27)2(OCH2CH2)3), 2.09, 2.01, 2.01
(3s, 9H, 3CH3COO), 1.97 (s, 3H, CH3CON), 1.63–1.48
(m, 4H, 2OCH2CH2C12H25), 1.39–1.20 (m, 44H, 22CH2
alkyl chains), 0.89 (t, 6H, J = 6.3 Hz, 2CH3 alkyl chains);
13C NMR (CDCl3): d 170.6, 170.6, 170.5, 169.2 (CH3CO),
101.8 (C-1), 78.3 (CH(CH2OC14H29)2), 73.4 (C-3), 71.7
(C-5), 71.6, 70.6, 68.6 (CH(CH2OCH2C13H27)2(OCH2
CH2)3), 68.7 (C-4), 62.2 (C-6), 53.8 (C-2), 31.9, 29.6, 29.5,
29.3, 29.1, 22.6 (CH2 alkyl chains), 23.0 (CH3CON), 20.7,
20.6, 20.5 (CH3COO), 14.0 (CH3 alkyl chains). Anal. Calcd
for C51H95NO14 (946.30): C, 64.73; H, 10.12; N, 1.48.
Found: C, 64.49; H, 10.16; N, 1.38.
1
[a]D = À6.1 (c 1.0, CHCl3); H NMR (CDCl3): d 5.86 (m,
1H, CH@), 5.32–5.10 (m, 4H, CH2@, H-3, NH), 5.05
(dd, 1H, J = 9.3, 9.6 Hz, H-4), 4.78 (d, 1H, J = 8.3 Hz,
H-1), 4.56–4.53 (m, 2H, allyl CH2), 4.27 (dd, 1H, J = 4.8,
12.2 Hz, H-6a), 4.11 (dd, 1H, J = 2.2, 12.2 Hz, H-6b),
4.02–3.92 (m, 1H, CH(CH2OCH2C11H23)2), 3.70–3.40 (m,
10H, H-2, H-5, CH(CH2OCH2C10H21)2), 2.08, 2.03, 2.02
(3s, 9H, 3CH3COO), 1.66–1.50 (m, 4H, 2OCH2-
CH2C9H19), 1.40–1.20 (m, 32H, 16CH2 alkyl chains),
0.88 (t, 6H, J = 6.5 Hz, 2CH3 alkyl chains); 13C NMR
(CDCl3):
d
170.5, 170.5, 169.4 (CH3COO), 155.9
4.21.2. 1,3-Bis(undecyloxy)prop-2-yl 2-acetamido-3,4,6-tri-
O-acetyl-2-deoxy-b-L-glucopyranoside 27. Compound 27
was prepared from 25 as described above. The 2-amino
intermediate was purified by column chromatography
(2:3 to 2:1 EtOAc–petroleum ether, Rf 0.80, 2:1 EtOAc–
petroleum ether); then, compound 27 was purified by col-
umn chromatography (3:2 EtOAc–petroleum ether) and
obtained as a solid (85%). Mp 93 ꢁC (EtOH); Rf 0.50 (1:1
(NHCOO), 132.8 (CH@), 117.3 (CH2@), 101.4 (C-1),
78.4 (CH(CH2OC11H23)2), 73.0 (C-3), 71.9, 71.8, 71.7,
71.6 (CH(CH2OCH2C10H21)2) 70.4 (C-5), 68.8 (C-4), 65.5
(allyl CH2), 62.3 (C-6), 56.2 (C-2), 31.9, 29.6, 29.5, 29.3,
26.1, 26.1, 22.6 (CH2 alkyl chains), 20.6, 20.6, 20.5
(CH3COO), 14.1 (CH3 alkyl chains). Anal. Calcd for
C41H73NO12 (772.00): C, 63.78; H, 9.53; N, 1.82. Found:
C, 64.01; H, 9.76; N, 1.72.
1
EtOAc–petroleum ether); [a]D = À1.0 (c 2.0, CHCl3); H
NMR (CDCl3): d 5.77 (d, 1H, J = 8.3 Hz, NH), 5.25 (dd,
1H, J = 10.3, 9.5 Hz, H-3), 5.12 (dd, 1H, J = 9.5, 9.5 Hz,
H-4), 4.89 (d, 1H, J = 8.5 Hz, H-1), 4.26 (dd, 1H,
J = 5.8, 12.2 Hz, H-6a), 4.12 (dd, 1H, J = 1.7, 12.2 Hz,
H-6b), 3.96–3.85 (m, 2H, OCH(CH2OC11H23)2, H-2),
3.70–3.34 (m, 9H, H-5, OCH(CH2OCH2C10H21)2), 2.08,
4.20.1. 1,3-Bis(undecyloxy)prop-2-yl 3,4,6-tri-O-acetyl-2-
allyloxycarbonylamino-2-deoxy-b-D-glucopyranoside 25-D.
Prepared as described above, from pentenyl glycoside 17
(0.229 g, 0.50 mmol) and 1,3-bis(undecyloxy)propan-2-
ol25 24 (0.200 g, 0.50 mmol). Product 25-D was obtained

3378
D. Lafont, P. Boullanger / Tetrahedron: Asymmetry 17 (2006) 3368–3379
2.02, 2.02 (3s, 9 H, 3CH3COO), 1.93 (s, 3H, CH3CON),
1.62–1.48 (m, 4H, 2OCH2CH2C9H19), 1.30–1.18 (m, 32H,
16CH2 alkyl chains), 0.88 (t, 6H, J = 6.4 Hz, 2CH3 alkyl
chains); 13C NMR (CDCl3): d 170.7, 170.6, 170.8, 169.3
(CH3CO) 101.1 (C-1), 78.2 (CH(CH2OC11H23)2), 73.0
(C-3), 71.8 (C-5), 71.9, 71.7, 71.6, 70.3 (CH(CH2O-
CH2C10H21)2), 68.7 (C-4), 62.3 (C-6), 54.8 (C-2), 31.9,
29.7, 29.6, 29.5, 29.3, 26.2, 26.1, 22.6 (CH2 alkyl chains),
23.2 (CH3CON), 20.7, 20.7, 20.6 (CH3COO), 14.1 (CH3
alkyl chains). Anal. Calcd for C39H71NO11 (729.97): C,
64.17; H, 9.80; N, 1.92. Found: C, 64.34; H, 9.99; N, 1.82.
4.22.3. 10-Tetradecyloxymethyl-3,6,9,12-tetraoxahexacosyl
2-acetamido-2-deoxy-b-L-glucopyranoside 30. Compound
30 was obtained as an amorphous solid in 94% yield from
26 as described above. [a]D = +26.0 (c 1.0, CHCl3); 1H
NMR (CDCl3): d 4.62 (d, 1H, J = 8.1 Hz, H-1), 3.95–
3.40 (m, 27H, OCH(CH2OCH2C13H27)2(OCH2CH2)3, H-
2, H-3, H-4, H-5, H-6a, H-6b), 2.07 (s, 3H, CH3CON),
1.65–1.48 (m, 4H, 2OCH2CH2C12H25), 1.39–1.20 (m,
44H, 22CH2 alkyl chains), 0.89 (t, 6H, J = 6.3 Hz, 2CH3
alkyl chains); 13C NMR (CDCl3): d 172.7 (CH3CO),
101.3 (C-1), 78.3 (CH(CH2OC14H29)2), 75.9, 75.2 (C-3,
C-5), 71.6, 71.3, 70.9, 69.4, 68.5 (CH(CH2OCH2-
C13H27)2(OCH2 CH2)3), 68.5 (C-4), 61.6 (C-6), 56.2 (C-2),
31.8, 29.6, 29.6, 29.5, 29.4, 29.3, 26.0, 22.6 (CH2 alkyl
chains), 22.8 (CH3CON), 14.0 (CH3 alkyl chains). Anal.
Calcd for C45H89NO11, H2O (838.21): C, 64.48; H, 10.94;
N, 1.67. Found: C, 64.25; H, 10.96; N, 1.58.
4.21.3. 1,3-Bis(undecyloxy)prop-2-yl 2-acetamido-3,4,6-tri-
O-acetyl-2-deoxy-b-D-glucopyranoside 27-D. Compound
27-D was synthesized from 25-D as described for 27. Prod-
uct 27-D was obtained in 81% yield. Mp 93–94 ꢁC;
[a]D = +0.8 (c 5.0, CHCl3); 1H and 13C NMR spectra were
identical to those of compound 27. Anal. Calcd for
C39H71NO11 (729.97): C, 64.17; H, 9.80; N, 1.92. Found:
C, 63.91; H, 9.64; N, 1.85.
4.22.4. 1,3-Bis(undecyloxy)prop-2-yl 2-acetamido-2-deoxy-
b-L-glucopyranoside 31. Compound 31 was obtained in
95% yield from 27 as described above. Mp 136–138 ꢁC;
[a]D = +16.0 (c 1.0, CHCl3); 1H NMR (2:1 CDCl3-
CD3OD): d 4.52 (d, 1H, J = 7.3 Hz, H-1), 3.88 (m, 1H,
OCH(CH2OC11H23)2), 3.79 (dd, 1H, J = 2.3, 12.2 Hz, H-
6a), 3.67 (dd, 1H, J = 4.8, 12.2 Hz, H-6b), 3.60–3.22 (m,
16H, NH, H-2, H-3, H-4, H-5, 3OH, OCH(CH2O-
CH2C10H21)2), 1.93 (s, 3H, CH3CON), 1.55–1.37 (m, 4H,
2OCH2CH2C9H19), 1.30–1.18 (m, 32H, 16CH2 alkyl
chains), 0.88 (t, 6H, J = 6.5 Hz, CH3 alkyl chains); 13C
NMR (2:1 CDCl3–CD3OD): d 172.8 (CH3CON) 100.9
(C-1), 77.8 (CH(CH2OC11H23)), 75.9, 75.4 (C-3, C-5),
71.7, 71.1, 70.6 (CH(CH2OCH2C10H21)), 70.7 (C-4), 61.6
(C-6), 57.2 (C-2), 31.8, 29.5, 29.3, 29.2, 29.3, 25.9, 26.1,
24.3, 22.5 (CH2 alkyl chains), 22.7 (CH3CON), 13.9 (CH3
alkyl chains). Anal. Calcd for C33H65NO8, H2O (621.89):
C, 63.73; H, 10.86; N, 2.25. Found: C, 63.70; H, 11.10;
N, 2.26.
4.22. General procedure for de-O-acetylation of compounds
9, 11, 26, 27, and 27-D
Compounds 9, 11, 26, 27, and 27-D (0.25–0.35 mmol) were
treated overnight in a CH2Cl2–MeOH mixture (1:1, 25 mL,
compound 9) or in pure MeOH (25 mL, compounds 11, 26,
27, and 27-D) containing a chip of sodium. Insoluble com-
pound 28 was isolated by filtration and washing with cold
MeOH. Pure products 29, 30, 31, and 31-D were obtained
after neutralization of the solution with amberlyst IR 120
[H+], filtration, and concentration.
4.22.1. Cholesteryl 2-acetamido-2-deoxy-b-L-glucopyrano-
side 28. Obtained in 93% yield from 9. Mp 235 ꢁC (EtOH)
(decomp); [a]D = À4.3 (c 0.6, 4:1 CHCl3–MeOH); 1H
NMR (2:1 CDCl3-CD3OD): d 5.28 (m, 1H, H-6Chol), 4.58
(d, 1H, J = 8.2 Hz, H-1), 3.81 (dd, 1H, J = 2.7, 12.3 Hz,
H-6a), 3.71 (dd, 1H, J = 4.1, 12.3 Hz, H-6b), 3.60–3.22
(m, 5H, H-2, H-3, H-4, H-5, H-3Chol), 2.07 (s, 3H,
CH3CON), 2.28–0.68 (m, 43H, H cholesterol). Anal. Calcd
for C35H59NO6Æ2.5H2O (634.89): C, 66.20; H, 10.16; N,
2.21. Found: C, 66.06; H, 9.86; N, 2.07.
4.22.5. 1,3-Bis(undecyloxy)prop-2-yl 2-acetamido-2-deoxy-
b-D-glucopyranoside 31-D. Compound 31-D was obtained
in 95% yield from 27-D as described above. Mp 134–
1
136 ꢁC; [a]D = À15.9 (c 1.0, CHCl3); H and 13C NMR
spectra were identical with those of compound 31. Anal.
Calcd for C33H65NO8, H2O (621.89): C, 63.73; H, 10.86;
N, 2.25. Found: C, 63.63; H, 10.94; N, 2.15.
4.22.2. 10-Undecyloxymethyl-3,6,9,12-tetraoxatricosyl 2-
acetamido-2-deoxy-b-L-glucopyranoside (29). Compound
29 was obtained in 95% yield from 10 as an amorphous
1
solid. [a]D = +29.2 (c 1.0, CHCl3); H NMR (CD3OD): d
References
4.48 (d, 1H, J = 8.3 Hz, H-1), 3.37–3.93 (m, 1H, OCH-
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