Syntheses of neoglycolipids with hexitol spacers between the saccharidic and the lipidic parts

Article abstract of DOI:10.1016/S0008-6215(01)00019-2

Four neoglycolipids having 2-amino-2-deoxy-D-glucose or D-galactose moieties linked to the lipidic part by a glucitol or a mannitol spacer-arm have been synthesized. The key step of the synthetic strategy was the regiospecific or regioselective β-glycosyl

Full text of DOI:10.1016/S0008-6215(01)00019-2

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Carbohydrate Research 331 (2001) 107–117
Syntheses of neoglycolipids with hexitol spacers between
the saccharidic and the lipidic parts
Dominique Lafont,* Barbara Gross,1 Rene Kleinegesse,1 Fabienne Dumoulin,
Paul Boullanger
Laboratoire de Chimie Organique II, Unite´ Mixte de Recherche CNRS 5622, Uni6ersite´ Lyon 1,
Chimie Physique Electronique de Lyon, 43 Boule6ard du 11 No6embre 1918, F-69622 Villeurbanne, France
Received 23 November 2000; accepted 18 January 2001
Abstract
Four neoglycolipids having 2-amino-2-deoxy-D-glucose or D-galactose moieties linked to the lipidic part by a
glucitol or a mannitol spacer-arm have been synthesized. The key step of the synthetic strategy was the regiospecific
or regioselective b-glycosylation of partially protected glucitol or mannitol acceptors by either 3,4,6-tri-O-acetyl-2-de-
oxy-2-iodo-a-
D
-mannopyranosyl azide or 2,3,4,6-tetra-O-benzoyl-a-D-galactopyranosyl trichloroacetimidate donors.
© 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Neoglycolipids; Glycosylation; Staudinger reaction; Imidate; Mannitol; Glucitol
1. Introduction
2. Results and discussion
To our knowledge, chemical glycosylation
In a series of studies directed towards the
understanding
of
self-organization
of
of a -hexitol on one of its primary hydroxyl
D
(neo)glycolipids with regard to their struc-
tures, we have recently synthesized several
compounds with a carbohydrate hydrophilic
head and two hydrophobic chains sometimes
separated by an oligoethyleneglycol spacer.
These compounds displayed thermotropic, as
well as lyotropic properties, and the carbohy-
drate moiety could be used as a recognition
signal towards lectins in supramolecular as-
semblies such as monolayers1,2 or liposomes.3
This paper deals with a synthesis of new class
of neoglycolipids in which the carbohydrate
head is separated from its hydrophobic alkyl
chains by an hexitol spacer.
groups had never been reported in the litera-
ture; however, 1-O-glycosylated hexitols could
be obtained by reduction of the reducing end
of disaccharides or oligosaccharides.4–6 In the
present case, O-5 and O-6 hydroxyl groups are
etherified with fatty alkyl chains prior to gly-
cosylation, which constrained us to realize the
glycosylation on the linear
D
-hexitol.
The first part of our syntheses was the
preparation of the acceptors which is depicted
in Scheme 1. Thus, in order to obtain a gluci-
tol derivative having two fatty alkyl chains at
O-5 and O-6, we started from the known
3-O-benzyl-1,2-O-isopropylidene-a- -gluco-
D
furanose (1) prepared according to Fleet et
al.7 Two tetradecyl residues were incorporated
on the free hydroxyl groups by reacting 1
which tetradecyl bromide at 80 °C under
* Corresponding author.
E-mail address: lafont@univ-lyon1.fr (D. Lafont).
1 On leave from the University of Stuttgart.
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00019-2

108
D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
dene-5,6-di-O-tetradecyl-
83% yield.
Glycosylation reaction was first attempted
using 3-O-benzyl-5,6-di-O-tetradecyl- -gluci-
tol (4) as the acceptor, 1,3,4,6-tetra-O-acetyl-
-gluco-
D-mannitol (10) in
D
2-allyloxycarbonylamino-2-deoxy-b-
D
pyranose11 as the donor and trimethylsilyl
trifluoromethanesulfonate as the promotor.
Previous work in the laboratory has shown
the high reactivity of this donor.11–13 How-
ever, in the present case, this high reactivity
was a disadvantage, and a complex mixture
was obtained — probably mono- and di-gly-
cosylated products — even at −30 °C. We
decided to use 3,4,6-tri-O-acetyl-2-deoxy-2-
Scheme 1.
iodo-a-
-mannopyranosyl azide (11)14 as the
D
glucosamine donor: this compound reacts in
the presence of triphenylphosphine with reac-
tive alcohol, through the formation of a 1,2-
aziridine intermediate, leading to b-derivatives
phase transfer conditions, in the presence of
50% aqueous sodium hydroxide and tetra-
butylammonium bromide. Treatment of the
di-O-tetradecyl ether (2) (obtained in 63%
yield) with dilute sulfuric acid in refluxing
dioxane afforded an a/b mixture of 3-O-ben-
in the 2-amino-2-deoxy- -glucose series, after
D
double inversion of configuration at C-1 and
C-2. Furthermore, it can be prepared in high
yield from 1,3,4,6-tetra-O-acetyl-2-deoxy-2-
zyl-5,6-di-O-tetradecyl-
yield. Then, the 3-O-benzyl-5,6-di-O-tetra-
decyl- -glucitol (4) was synthesized from
D
-glucose (3) in 93%
iodo-a-
-mannopyranose15 and trimethylsilyl
D
azide in the presence of trimethylsilyl tri-
fuoromethanesulfonate. Thus, the glycosyla-
tion of the alcohol 4 by the glycosyl azide 11,
in the presence of a slight excess of
triphenylphosphine afforded the iodot-
riphenylphosphonioamino salt 12 in 76% yield
(Scheme 2). The structure of this salt was
D
derivative 3 by reduction with sodium borohy-
dride in a 1:1 chloroform–ethanol mixture
(77% yield).
Analogs in the
D-mannitol series were syn-
thesized by two different routes. Thus, starting
1
13
from the known 1,2:3,4-di-O-cyclohexylidene-
ascertained by H and C NMR spectroscopy
and comparison with literature data.14–16 Con-
version of the salt 12 to the acetamido deriva-
tive 13 was achieved by standard procedure
and the overall glycosylation yield was 58%.
O-Debenzylation (H2, Pd/C, EtOAc) followed
by reacetylation gave the peracetylated disac-
charide 14 in 91% yield. The analogue in the
mannitol series 16 was directly obtained by
glycosylation of the tetraol 9 with the same
donor 11 in a lower yield (53%); that could be
due to the low solubility of the acceptor in
methylene chloride. However, as in the gluci-
tol series, the formation of bis(glycosylated)
derivatives was not observed.
D
-mannitol (5),8 we could obtain, as described
for the preparation of 2 from 1, the 5,6-di-O-
tetradecyl derivative 7 in 50% yield. Cleavage
of the cyclohexylidene groups was realized
under harsh conditions, by treatment with 2 N
hydrochloric acid in refluxing dioxane. The
expected 5,6-di-O-tetradecyl- -mannitol (9)
D
was recovered in 40% yield. We also prepared
a second acceptor, with only two free hy-
droxyl groups. Thus, 1,2:3,4-di-O-(isopropyli-
dene)-5,6-di-O-tetradecyl-
synthesized in 56% yield from the known
1,2:3,4-di-O-isopropylidene-
-mannitol (6)9 as
D
-mannitol (8) was
D
described above for 2 and 7; selective depro-
tection of the terminal isopropylidene group
of 8 occurred with a high regioselectivity using
an excess of zinc nitrate hexahydrate in aceto-
nitrile at 50 °C,10 affording 3,4-O-isopropyli-
The structure of the disaccharides 14 and 16
was fully assigned on the basis of COSY
1
1H–1H and H–13C 2D experiments in chloro-
1
form-d at 500 MHz. H NMR chemical shift

D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
109
AcOH, 90 °C, 14 h) affording 22, which was
debenzoylated before reacetylation. As for the
glucosamine derivatives, the structure of
derivatives 18, 20, 22 and 23 was ascertained
from 500 MHz NMR spectra.
O-Deacetylation of the peracetylated disac-
charides 14, 16, 20 and 23 by the Zemple´n
procedure gave the fully deprotected deriva-
tives 24–27 in high yields.
3. Experimental
General methods.—Pyridine was dried by
boiling with CaH2 prior to distillation.
Dichloromethane was washed twice with wa-
ter, dried with CaCl2 and distilled from CaH2.
,
Pyridine and CH2Cl2 were stored over 4 A
molecular sieves. Melting points were deter-
mined on a Bu¨chi apparatus and were uncor-
rected. Thin layer chromatography was
performed on aluminum sheets coated with
Silica gel 60 F254 (E. Merck). Compounds
Scheme 2.
for H-2, H-3 and H-4 of the hexitol residues
(l 5.50–5.00 ppm) as well as 13C chemical
shift for C-1 (l 67.00–67.50 ppm) confirmed
the presence of acetyl protecting groups at
C-2, C-3 and C-4 and the glycosylation at C-1.
Galactosylated derivatives were also synthe-
sized by reacting the acceptors 4 and 10 with
the known 2,3,4,6-tetra-O-benzoyl-a- -galac-
D
topyranosyl trichloroacetimidate 1717 in meth-
ylene chloride at 0 °C, using trimethylsilyl
trifluoromethanesulfonate as the promotor
(Scheme 3). Glycosides 18 and 21 were, re-
spectively, obtained in 57 and 80% yield; the
lower yield observed from 18 was due to the
formation of bis(glycosylation) products
which were not identified. Compound 18 was
successively transformed into 19 by hy-
drogenolysis [Pd(OH)2/C, cyclohexene, etha-
nol] followed by O-debenzoylation and
O-reacetylation by standard procedures, to af-
ford the peracetylated product 20 in good
yield. Disaccharide 23 was also prepared in
high yield from 21 by cleavage of the iso-
propylidene group in acidic medium (80% aq
Scheme 3.

110
D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
H2SO4 were refluxed for 3.5 h, until TLC
showed complete disappearance of the starting
material. After neutralization with satd
NaHCO3 solution, the volatiles were evapo-
rated and the residue was diluted with water
(50 mL). The aqueous phase was extracted
with CH2Cl2 (3×50 mL) and the combined
organic phases were dried (Na2SO4) and con-
centrated. The resulting syrup was purified by
flash chromatography (2:1 petroleum ether–
EtOAc) to provide 3 (3:2 a/b mixture) as an
oil (3.08 g, 93%). [h]D −6.2° (c 1.0, CHCl3);
1H NMR (CDCl3): l 7.33–7.26 (m, 5 H,
C6H5), 5.49 (dd, 0.6 H, J1,2 4.1, J1,OH 6.5 Hz,
H-1a), 5.11 (d, 0.4 H, J1,OH 12.1 Hz, H-1b);
13C NMR (CDCl3): l 103.45 (C-1b), 96.81
(C-1a). Anal. Calcd for C41H74O6 (663.00): C,
74.27; H, 11.25. Found; C, 73.74; H, 11.18.
were visualized by spraying the TLC plates
with dilute 15% aq H2SO4, followed by char-
ring at 150 °C for a few minutes. Column
chromatography was performed on Silica-gel
Geduran Si 60 (E. Merck). Optical rotations
were recorded on a Perkin–Elmer 241 polar-
1
imeter in a 1 dm cell at 21 °C. H and 13C
NMR spectra were recorded with Bruker AC-
200 or DRX-500 spectrometers working at
200 or 500 MHz and 50 or 125 MHz, respec-
tively, with Me4Si as the internal standard.
The assignments of 13C NMR spectra for
compounds 14, 16, 18, 20, 22 and 23 were
based on 1H–13C HMQC experiments in
CDCl3 at 500 MHz. For compounds 4, 7–9,
10, 12, 13, 15, 19 and 21, 13C assignments were
tentatives. Elemental analyses were performed
by the Laboratoire Central d’Analyses du
CNRS (Vernaison, France).
3-O-Benzyl-5,6-di-O-tetradecyl- -glucitol
D
3-O-Benzyl-1,2-O-isopropylidene-5,6-di-O-
(4).—A solution of NaBH4 (1.00 g, 26.43
tetradecyl-h-
D
-glucofuranose (2).—A suspen-
mmol) in water (25 mL) was added to a
sion of 3-O-benzyl-1,2-O-isopropylidene-
solution of 3-O-benzyl-5,6-di-O-tetradecyl- -
D
a-D
-glucofuranose (1)7 (5.00 g, 16.11 mmol) in
glucofuranose (3) (3.00 g, 4.52 mmol) in 1:2
CHCl3–EtOH (75 mL) and the mixture was
stirred at rt for 15 h. After neutralization with
an Amberlyst IR 120 (H+) resin, the solution
was diluted with a 1:1 CHCl3–EtOH mixture
(200 mL); filtration and concentration of the
solution provided a residue which was purified
by column chromatography (1:1 petroleum
ether–EtOAc) affording the pure product 4 as
a solid (2.30 g, 77%). Mp 49 °C (EtOH); [h]D
−14.4° (c 1.0, CHCl3); Rf 0.52 (1:1 petroleum
50% NaOH solution (22.0 mL) was stirred for
1 h at 80 °C, until complete homogenization;
tetradecyl bromide (20 mL, 67.2 mmol) and
Bu4NBr (2.00 g, 6.20 mmol) were then added
and heating was maintained for 6 h. After
cooling and addition of water, the reaction
mixture was extracted three times with CHCl3
(3×40 mL) and the combined organic phases
were washed with water (30 mL), dried
(Na2SO4) and concentrated. The residue was
purified by silica-gel column chromatography
(35:1 petroleum ether–EtOAc) affording 2
(7.14 g, 63%) as an oil. [h]D −18.8° (c 1.0,
1
ether–EtOAc); H NMR (CDCl3): l 7.36–
7.25 (m, 5 H, C6H5), 4.70 (s, 2 H, CH2Ph),
3.86–3.23 (m, 13 H, H-1a, H-1b, H-2, H-3,
H-4, H-5, H-6a, H-6b, OH, 2 OCH2), 2.9–
32.90 (m, 2 H, 2 OH), 1.52 (m, 4 H, 2
OCH2CH2), 1.29 (m, 44 H, 22 CH2 alkyl
1
CHCl3); H NMR (CDCl3): l 7.33 (m, 5 H,
C6H5), 5.90 (d, 1 H, J1,2 3.7 Hz, H-1), 4.96 and
4.68 (2 d, 2 H, J 11.6 Hz, CH2Ph), 4.59 (d, 1
H, H-2), 4.21 (dd, 1 H, J3,4 2.9, J4,5 9.1 Hz,
H-4), 4.08 (d, 1 H, H-3), 3.83–3.22 (m, 7 H,
H-5, H-6a, H-6b, 2 OCH2), 1.60, 1.53 (m, 4 H,
2 OCH2CH2), 1.48 (2 s, 6 H, C(CH3)2), 1.34
(m, 44 H, 22 CH2 alkyl chains), 0.88 (t, 6 H,
2 CH3 alkyl chains). Anal. Calcd for C44H78O6
(703.06): C, 75.16; H, 11.18. Found; C, 75.12;
H, 11.04.
13
chains), 0.88 (t, 6 H, 2 CH3 alkyl chains); C
NMR (CDCl3): l 138.11, 128.55–128.05 (6 C,
C6H5), 77.99, 77.55 (C-3, C-5), 74.25
(CH2C6H5), 71.95 (OCH2), 71.69, 71.17 (C-
2,4), 70.49 (C-6), 70.28 (OCH2), 62.48 (C-1),
31.97, 30.22, 29.74, 29.56, 29.53, 29.41, 26.27,
26.16, 22.74 (CH2 alkyl chains), 14.15 (2 C, 2
CH3 alkyl chains). Anal. Calcd for C41H76O6
(665.02): C, 74.04; H, 11.52. Found; C, 73.79;
H, 11.58.
3-O-Benzyl-5,6-di-O-tetradecyl-
nose (3).—3-O-Benzyl-1,2-O-isopropylidene-
5,6-di-O-tetradecyl-a- -glucofuranose (2)
(3.52 g, 5.00 mmol), dioxane (60 mL) and 1 N
D-glucofura-
D
1,2:3,4-Di-O-cyclohexylidene-5,6-di-O-tetra-
decyl- -mannitol (7).—A suspension of
D

D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
111
1,2:3,4-di-O-cyclohexylidene-
-mannitol (5)8
D
C40H78O6 (655.02): C, 73.34; H, 12.00. Found;
C, 73.53; H, 12.20.
(2.50 g, 7.30 mmol) in 50% NaOH solution
(8.5 mL) was stirred for 1 h at 80 °C, until
complete homogenization. Tetradecyl bromide
(8.8 mL, 29.6 mmol) and Bu4NBr (0.94, 2.91
mmol) were then added and heating was
maintained for 8 h at 80 °C. After cooling and
addition of water, the reaction mixture was
extracted three times with CHCl3 (3×50 mL)
and the combined organic phases were washed
with water (30 mL), dried (Na2SO4) and con-
centrated. The residue was purified by silica-
gel column chromatography (20:1 petroleum
ether–EtOAc) affording 7 (2.68 g, 50%) as an
oil. [h]D +10.3° (c 1.0, CHCl3); Rf 0.26 (40:1
5,6-Di-O-tetradecyl-D-mannitol
(9).—A
mixture of 7 (2.35 g, 3.20 mmol), dioxane (15
mL) and 2 N HCl (5.5 mL) was stirred for 8
h at 90 °C. After cooling to rt, the solution
was neutralized with satd NaHCO3 solution,
and concentrated. The residue was extracted
with EtOAc (3×30 mL) and the combined
organic phases were dried (Na2SO4) and con-
centrated again. The crude product was
purified by column chromatography (EtOAc)
affording a white solid which was recrystal-
lized from EtOH: 0.74 g, 40% yield. Mp 85 °C
(EtOH), [h]D −5.5° (c 1.0, CHCl3), Rf 0.55
1
1
petroleum ether–EtOAc); H NMR (CDCl3):
(EtOAc); H NMR (CDCl3): l 3.93–3.43 (m,
l 4.26–3.40 (m, 12 H, H-1a, H-1b, H-2, H-3,
H-4, H-5, H-6a, H-6b, 2 OCH2), 1.58 (m, 24
H, 2 OCH2CH2, 10 CH2 cyclohexyl), 1.26 (m,
44 H, 22 CH2 alkyl chains), 0.88 (t, 6 H, 2
CH3 alkyl chains); 13C NMR (CDCl3): l
110.18, 110.09 (2 C, 2 C(CH2)2), 79.49, 79.35,
78.32, 76.98 (C-2, C-3, C-4, C-5), 71.55, 70.38
(2 OCH2), 70.81 (C-6), 66.59 (C-1), 37.01,
36.95, 36.21, 35.07, 31.97 (4 C, 2 C(CH2)2),
30.11–29.41, 26.21, 26.18, 25.24, 24.05, 24.00,
23.92, 22.74 (CH2 alkyl chains and cyclo-
hexyl), 14.14 (2 C, 2 CH3 alkyl chains). Anal
Calcd for C46H86O6 (735.148): C, 75.15; H,
11.79. Found; C, 75.00; H, 11.61.
13 H, H-1a, H-1b, H-2, H-3, H-4, H-5, H-6a,
H-6b, OH, 2 OCH2 alkyl chains), 3.32, 2.97,
2.52 (3 m, 3 H, 3 OH), 1.56 (m, 4 H, 2
OCH2CH2), 1.26 (m, 44 H, 22 CH2 alkyl
13
chains), 0.88 (t, 6 H, 2 CH3 alkyl chains); C
NMR (CDCl3): l 78.92 (C-5), 71.70, 70.23,
69.29 (3 C, C-2, C-3, C-4), 71.61, 70.36 (2
OCH2), 70.96 (C-6), 63.63 (C-1), 31.65,
20.79–29.08, 25.81, 22.38 (CH2 alkyl chains),
14.14 (2 C, 2 CH3 alkyl chains). Anal. Calcd
for C34H70O6 (574.90): C, 71.03; H, 12.27.
Found; C, 70.92; H, 12.44.
3,4-O-Isopropylidene-5,6-di-O-tetradecyl-
mannitol (10).—To a solution of 1,2:3,4-di-O-
isopropylidene-5,6-di-O-tetradecyl- -mannitol
D-
1,2:3,4-Di-O-isopropylidene-5,6-di-O-tetra-
D
decyl-
D
-mannitol (8).—Prepared from 1,2:3,4-
(8) (0.655 g, 1.00 mmol) in MeCN (5 mL) was
added Zn(NO3)2·6 H2O (1.49 g, 5.00 mmol)
and the mixture was stirred at 50 °C for 8 h.
After cooling, the solution was concentrated
and the oily residue, diluted with CH2Cl2 (15
mL), washed with water and dried (Na2SO4).
Evaporation of the volatiles and purification
of the crude product by column chromatogra-
phy (3:1 petroleum ether–EtOAc) afforded 10
(0.510 g, 83%) as a solid. An analytical sample
was recrystallized from EtOH. Mp 55 °C; [h]D
di-O-isopropylidene-
D
-mannitol (6)9 (3.00 g,
11.44 mmol) as described for 7. The crude
product was purified by silica-gel column
chromatography (10:1 petroleum ether–
EtOAc) affording 8 (4.75 g, 56%) as an oil.
1
[h]D +7.0° (c 1.0, CHCl3); Rf 0.50; H NMR
(CDCl3): l 4.20–3.40 (m, 12 H, H-1a, H-1b,
H-2, H-3, H-4, H-5, H-6, H-6b, 2 OCH2 alkyl
chains), 1.60 (m, 4 H, 2 OCH2CH2), 1.43,
1.40, 1.38, 1.35 (4 s, 12 H, 2 C(CH3)2), 1.26
(m, 44 H, 22 CH2 alkyl chains), 0.88 (t, 6 H,
2 CH3 alkyl chains); 13C NMR (CDCl3): l
109.67, 109.46 (2 C, 2 C(CH3)2), 79.55, 79.18,
78.46, 77.03 (4 C, C-2, C-3, C-4, C-5), 71.56,
71.32 (2 C, 2 OCH2CH2), 70.34 (C-6), 66.58
(C-1), 31.90, 30.10–29.40 (CH2 alkyl chains),
27.31, 27.28, 26.55, 25.42 (4 C, 2 C(CH3)2),
26.20, 26.16, 22.71 (CH2 alkyl chains), 14.12
(2 C, 2 CH3 alkyl chains). Anal. Calcd for
1
−3.0° (c 1.0, CHCl3); Rf 0.55; H NMR
(CDCl3): l 4.15 (d, 1 H, OH), 3.74–3.38 (m,
12 H, H-1a, H-1b, H-2, H-3, H-4, H-5, H-6a,
H-6b, 2 OCH2), 2.35 (dd, 1 H, CH2OH), 1.58
(m, 4 H, 2 OCH2CH2), 1.39, 1.38 (2 s, 6 H,
C(CH3)2), 1.26 (m, 44 H, 22 CH2 alkyl
13
chains), 0.88 (t, 6 H, 2 CH3 alkyl chains); C
NMR (CDCl3): l 109.28 (C(CH3)2), 80.39,

112
D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
H-5, H-6a, H-6b, H-2%, H-5%, H-6%a, H-6%b, 2
OCH2), 2.05, 1.90, 1.70 (3 s, 9 H, 3 CH3COO),
1.28 (m, 48 H, 24 CH2 alkyl chains), 0.88 (t, 6
80.18, 78.50 (3 C, C-3, C-4, C-5), 73.07 (C-2),
71.62, 71.08 (2 C, 2 OCH2), 70.87 (C-6), 63.91
(C-1), 31.92, 29.70–29.36 (CH2 alkyl chains),
26.78 (2 C, C(CH3)2), 26.14, 25.93, 22.66 (CH2
alkyl chains), 14.06 (2 C, 2 CH3 alkyl chains).
Anal Calcd for C37H74O6 (614.96): C, 72.26;
H, 12.13. Found; C, 72.51; H, 12.34.
13
H, 2 CH3 alkyl chains); C NMR (CDCl3): l
170.57, 170.10, 169.10 (3 C, 3 CH3COO),
138.21, 135.00, 134.23, 134.00, 132.07–127.85
(21 C, 3 PC6H5 and CH2C6H5), 121.42 (d, 3 C,
JC,P 103.5 Hz, 3 C-ipso PC6H5), 100.21 (C-1%),
78.13 (C-5), 77.39 (C-3), 74.73 (C-3%), 74.24
(CH2C6H5), 72.19 (C-1), 71.86 (OCH2), 71.69,
71.29 (3 C, C-2, C-4, C-5%), 70.53 (C-6), 70.28
(OCH2), 69.32 (C-4%), 62.03 (C-6%), 57.98 (C-
2%), 31.93, 30.31, 29.72, 29.56, 29.37, 26.26,
26.18, 22.70 (CH2 alkyl chains), 20.70, 20.67,
20.46 (3 C, 3 CH3COO), 14.14 (2 C, 2 CH3
alkyl chains).
3,4,6-Tri-O-acetyl-2-deoxy-2-iodo-h- -
D
mannopyranosyl azide (11).—Trimethysilyl
azide (1.00 mL, 7.60 mmol) and Me3SiOTf
(250 mL, 0.98 mmol) were successively added
to a solution of 1,3,4,6-tetra-O-acetyl-2-de-
oxy-iodo-a-
-mannopyranose15 (2.05 g, 4.47
D
mmol) in CH2Cl2 (10 mL); the mixture was
stirred for 15 h, and then poured into a satd
NaHCO3 solution (15 mL). The product was
extracted with CH2Cl2 (3×25 mL), and the
combined organic phases were washed with
water (20 mL), dried (Na2SO4) and concen-
trated. The residue was purified on a short
column of silica-gel (1:1 petroleum ether–
AcOEt) to afford the pure product 11 as an
oil (1.88 g, 95%); [h]2D0 +81.2° (c 2, CHCl3);
lit.14 [h]2D0 +80.4° (c 3, CHCl3).
Compound 12 was dissolved in a minimum
amount of EtOH, and the solution was ap-
plied on the top of a column packed with
Dowex 2X8 [OH−] resin and eluted with
EtOH. After concentration of the eluate, the
residue was treated overnight with a catalytic
amount of MeONa in MeOH (15 mL). Con-
centration followed by acetylation of the
residue with a 2:1 pyridine–Ac2O mixture (10
mL) afforded a crude compound which was
purified by column chromatography (1:5
petroleum ether–AcOEt) to provide the pure
product 13 as an oil (0.625 g, 58%). [h]D
1-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-de-
oxy-i-
D
-glucopyranosyl)-2,4-di-O-acetyl-3-O-
-glucitol (13).—
benzyl-5,6-di-O-tetradecyl-
D
Triphenylphosphine (0.288 g, 1.10 mmol) was
added quickly to a cooled solution (0 °C) of
1
3,4,6-tri-O-acetyl-2-iodo-2-deoxy-a-
pyranosyl azide (11) (0.441 g, 1.00 mmol) and
3-O-benzyl-5,6-di-O-tetradecyl- -glucitol (4)
D
-manno-
−18.9° (c 1.0, CHCl3); Rf 0.77; H NMR
(CDCl3): l 7.33 (m, 5 H, CH2C6H5), 5.24–
5.10 (m, 3 H, H-3%, H-2, H-4), 5.08 (dd, 1 H,
J3%,4%% 9.5, J4%,5%% 9.5 Hz, H-4%), 4.69 (s, 2 H,
CH2C6H5), 4.50 (d, 1 H, J1%,2% 8.4 Hz, H-1%),
4.29 (dd, 1 H, J5%,6%a 4.4, J6%a,6%b 12.4 Hz, H-6%a),
4.15–3.30 (m, 13 H, H-1a, H-1b, H-3, H-5,
H-6a, H-6b, H-2%, H-5%, H-6%b, 2 OCH2 alkyl
chains), 2.11, 2.08, 2.05, 2.02, 2.00, 1.92 (6 s,
18 H, 5 CH3COO, 1 CH3CON), 1.52 (m, 4 H,
2 OCH2CH2), 1.28 (m, 44 H, 22 CH2 alkyl
D
(0.652 g, 0.98 mmol) in CH2Cl2 (5 mL); the
mixture was allowed to reach rt and stirring
was maintained for 15 h. After concentration,
the residue was applied to the top of a short
column of silica-gel and eluted first with 1:1
petroleum ether–EtOAc, then with pure
EtOAc and finally with 4:1 EtOAc–EtOH
affording 1-O-(3,4,6-tri-O-acetyl-2-deoxy-2-
13
iodotriphenylphosphonioamino-b-
D
-glucopy-
chains), 0.88 (t, 6 H, 2 CH3 alkyl chains); C
ranosyl)-3-O-benzyl-5,6-di-O-tetradecyl-
D-
NMR (CDCl3): l 170.88, 170.79, 170.72,
170.38, 170.18, 169.32 (6 C, 6 CH3CO),
138.23, 128.46–127.59 (6 C, CH2C6H5), 99.07
(C-1%), 76.48 (C-5), 75.78 (C-3), 74.72
(CH2C6H5), 73.10 (C-3%), 71.92 (C-5%), 71.74
(OCH2), 71.31, 71.00 (C-2, C-4), 70.23 (C-6),
69.50 (OCH2), 68.47 (C-4%), 66.98 (C-1), 61.89
(C-6%), 54.10 (C-2%), 31.92, 30.08-29.35, 26.16,
26.08 (CH2 alkyl chains), 23.17 (CH3CON),
21.14, 21.06, 20.90, 20.72, 20.60 (5 C, 5
glucitol (12) (0.990 g, 76%) containing traces
of triphenylphospine oxide. Yellow amor-
1
phous solid; Rf 0.76 (4:1 EtOAc–EtOH); H
NMR (CDCl3): l 7.87–7.42 (m, 20 H,
CH2C6H5 and 3 PC6H5), 5.84 (dd, 1 H, J2%,3%
9.5, J3%,4% 9.5 Hz, H-3%), 5.71 (d, 1 H, J1%,2% 8.4
Hz, H-1%), 4.79 (dd, 1 H, J4%,5% 9.5 Hz, H-4%),
4.65 (dd, 2 H, J 11.7 Hz, CH2C6H5), 4.26–
3.03 (m, 16 H, H-1a, H-1b, H-2, H-3, H-4,

D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
113
5,6-di-O-tetradecyl-
D
-mannitol (16).—A solu-
CH3COO), 14.14 (2 C, 2 CH3 alkyl chains).
Anal. Calcd for C59H99NO16 (1078.39): C,
65.71; H, 9.25; N 1.30. Found; C, 65.44; H,
9.02; N, 1.37.
tion of 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-a- -
D
mannopyranosyl azide (11) (0.441 g, 1.00
mmol) in dry CH2Cl2 (5 mL) was added drop-
wise to a suspension of 5,6-di-O-tetradecyl- -
D
1-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-de-
mannitol (9) (0.470 g, 0.82 mmol) and PPh3
(0.288 g, 1.10 mmol) in CH2Cl2 (20 mL) and
the mixture was stirred overnight. After con-
centration, the residue was applied to the top
of a short column of silica-gel and eluted first
with pure EtOAc, then with 4:1 EtOAc–
EtOH affording 1-O-(3,4,6-tri-O-acetyl-2-de-
oxy-i-
D
-glucopyranosyl)-2,3,4-tri-O-acetyl-
-glucitol (14).—Com-
5,6-di-O-tetradecyl-
D
pound 13 (0.600 g, 0.56 mmol) in EtOAc (15
mL) was hydrogenated at rt under atmo-
spheric hydrogen pressure in the presence of
10% Pd/C (60 mg). The suspension was stirred
overnight. After filtration and concentration,
the crude residue was acetylated for 18 h in a
1:2 Ac2O–pyridine mixture (15 mL). The pure
compound 14 was obtained by concentration
of the solution, coevaporation from toluene
and column chromatography (1:5 petroleum
ether–EtOAc): 0.513 g, 91% yield. An analyti-
cal sample was recrystallized from EtOH; mp
73–74 °C; [h]D −15.4° (c 1.0, CHCl3); Rf
oxy - 2 - iodotriphenylphosphonioamino - b -
glucopyranosyl) - 5,6 - di - O - tetradecyl -
D
-
-
D
mannitol (15) containing approximately 10%
of starting alcohol 9 and traces of triphenyl-
phospine oxide. Yellow amorphous solid; Rf
1
0.70 (4:1 EtOAc–EtOH); H NMR (CDCl3):
l 5.83 (dd, 1 H, J2%,3% 9.8, J3%,4% 9.3 Hz, H-3%),
5.78 (d, 1 H, J1%,2% 8.0 Hz, H-1%), 4.79 (dd, 1 H,
J4%,5% 9.2 Hz, H-4%), 4.25–2.95 (m, 19 H, H-1a,
H-1b, H-2, H-3, H-4, H-5, H-6a, H-6b, H-2%,
H-5%, H-6%a, H-6%b, 3 OH, 2 OCH2 alkyl
chains), 2.03, 1.99, 1.68 (3 s, 9 H, 3
CH3COO), 1.28 (m, 48 H, 24 CH2 alkyl
chains, 0.88 (t, 6 H, 2 CH3 alkyl chains); 13C
NMR (CDCl3): l 170.62, 169.88, 169.28 (3 C,
3 CH3COO), 135.02, 134.18, 133.96, 132.01-
128.58 (15 C, 3 PC6H5), 120.95 (d, 3 C, JC,P
104.1 Hz, 3 C-ipso PC6H5), 100.82 (C-1%),
79.09 (C-5), 74.52 (C-3%), 71.80, 71.18 (2 C,
C-6, OCH2), 71.11 (C-5%), 71.05, 70.13, 69.78,
69.35 (4 C, C-2, C-3, C-4, C-4%), 68.21
(OCH2), 66.51 (C-1), 61.83 (C-6%), 57.87 (C-
2%), 31.83, 30.09, 29.62–29.27, 26.02, 22.59
(CH2 alkyl chains), 20.68, 20.61, 20.37 (3 C, 3
CH3COO), 14.14 (2 C, 2 CH3 alkyl chains).
The salt 15 was treated as described for 12,
and the crude compound was purified by
column chromatography (1:5 petroleum
ether–AcOEt) to provide the pure product 16
as a solid (0.446 g, 53%). Mp 101–102 °C
(EtOH); [h]D −4.7° (c 1.0, CHCl3); Rf 0.65;
1H NMR (CDCl3): l 6.13 (d, 1 H, J2,NH 8.3
Hz, NH), 5.47 (dd, 1 H, J2,3 9.1, J3,4 2.0 Hz,
H-3), 5.22 (dd, 1 H, J4,5 1.5 Hz, H-4), 5.20
(dd, 1 H, J2%,3% 10.1, J3%,4% 9.6 Hz, H-3%), 5.08
(dd, 1 H, J4%,5% 9.8 Hz, H-4%), 4.98 (ddd, 1 H,
J1a,2 2.7, J1b,2 3.2 Hz, H-2), 4.42 (d, 1 H, J1%,2%
8.4 Hz, H-1%), 4.27 (dd, 1 H, J5%,6%a 4.9, J6%a,6%b
12.3 Hz, H-6%a), 4.08 (m, 2 H, H-1a, H-6%b),
3.98 (ddd, 1 H, H-2%), 3.57 (ddd, 1 H, J5%,6%b 2.3
1
0.65; H NMR (CDCl3): l 5.90 (d, 1 H, J2%,NH
8.5 Hz, NH), 5.47 (dd, 1 H, J2,3 5.6, J3,4 5.5
Hz, H-3), 5.25 (dd, 1 H, J2%,3% 10.0, J3%,4% 9.7 Hz,
H-3%), 5.23 (ddd, 1 H, J1a,2 7.0, J1b,2 4.5 Hz,
H-2), 5.20 (dd, 1 H, J4,5 10.4 Hz, H-4), 5.11
(dd, 1 H, J4%,5% 9.4 Hz, H-4%), 4.58 (d, 1 H, J1%,2%
8.4 Hz, H-1%), 4.31 (dd, 1 H, J5%,6%a 4.5, J6%a,6%b
12.3 Hz, H-6%a), 4.12 (dd, 1 H, J5%,6%b 1.2 Hz,
H-6%b), 3.89 (ddd, 1 H, H-2%), 3.86 (ddd, 1 H,
J1a,1b 11.7 Hz, H-1a), 3.75 (dd, 1 H, H-1b),
3.71 (ddd, 1 H, H-5%), 3.55 (dd, 1 H, J5,6a 4.6,
J6a,6b 10.0 Hz, H-6a), 3.50–3.37 (m, 6 H, H-5,
H-6b, 2 OCH2), 2.10, 2.09, 2.09, 2.08, 2.02,
2.01, 1.96 (7 s, 21 H, 6 CH3COO, 1
CH3CON), 1.52 (m, 4 H, 2 OCH2CH2), 1.26
(m, 44 H, 22 CH2 alkyl chains), 0.88 (t, 6 H,
2 CH3 alkyl chains); 13C NMR (CDCl3): l
170.64, 170.61, 170.32, 170.32, 170.00, 169.90,
169.26 (7 C, 7 CH3CO), 99.85 (C-1%), 76.83
(C-5), 73.37 (C-3%), 72.23 (C-5%), 72.15
(OCH2), 71.44 (OCH2), 70.65 (C-4), 69.80 (C-
3), 69.69 (C-6), 69.54 (C-2), 68.80 (C-4%), 67.16
(C-1), 62.19 (C-6%), 54.59 (C-2%), 31.88, 29.82,
29.65-29.35, 26.00, 25.96 (CH2 alkyl chains),
23.40 (CH3CON), 21.12, 20.90, 20.90, 20.60,
20.60, 20.60 (6 C, 6 CH3COO), 14.06 (2 C, 2
CH3 alkyl chains). Anal. Calcd for
C54H95NO17 (1030.31): C, 62.95; H, 9.29; N
1.36. Found; C, 62.96; H, 9.40; N, 1.63.
1-O-(2-Acetamido-3,4,6-tri-O-acetyl-2-de-
oxy-i- -glucopyranosyl)-2,3,4-tri-O-acetyl-
D

114
D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
Hz, OH), 1.55 (m, 4 H, 2 OCH2CH2), 1.27 (m,
44 H, 22 CH2 alkyl chains), 0.90 (t, 6 H, 2
CH3 alkyl chains); 13C NMR (CDCl3): l
Hz, H-5%), 3.57 (dq, 1 H, 0.5 OCH2), 3.49–
3.33 (m, 6 H, H-5, H-6a, H-6b, 1.5 OCH2),
3.31 (dd, 1 H, J1a,1b 11.6 Hz, H-1b), 2.14, 2.08,
2.05, 2.05, 2.02, 2.01, 1.97 (7 s, 21 H, 6
CH3COO, 1 CH3CON), 1.52 (m, 4 H, 2
OCH2CH2), 1.26 (m, 44 H, 22 CH2 alkyl
166.12, 165.63, 165.6, 165.34 (4 C,
4
C6H5COO), 138.23, 133.67–133.27, 130.09-
127.84 (30 C, 5 C6H5), 102.26 (C-1%), 78.35
(C-5), 76.91 (C-3), 74.28 (CH2C6H5), 72.63
(C-1), 71.82 (OCH2), 71.79–71.72 (4 C, C-2,
C-4, C-3%, C-5%), 70.59 (C-6), 70.31 (OCH2),
69.92 (C-2%), 68.29 (C-4%), 62.35 (C-6%), 32.00,
30.24–29.45, 26.23, 22.77 (CH2 alkyl chains),
14.18 (2 C, 2 CH3 alkyl chains). Anal. Calcd
for C75H102NO15 (1243.57): C, 72.43; H, 8.27.
Found; C, 72.34; H, 8.46.
13
chains), 0.88 (t, 6 H, 2 CH3 alkyl chains); C
NMR (CDCl3): l 170.40, 170.30, 170.30,
170.06, 170.06, 169.82, 169.30 (7 C, 7
CH3CO), 101.15 (C-1%), 77.01 (C-5), 73.55 (C-
3%), 72.43 (C-5%), 72.18, 71.64 (2 C, 2 OCH2),
71.16 (C-6), 70.04 (C-4), 68.87 (C-2, C-4%),
68.67 (C-3), 67.58 (C-1), 62.47 (C-6%), 54.58
(C-2%), 32.36, 30.32–29.69, 26.44, 26.30 (CH2
alkyl chains), 23.45 (CH3CON), 21.32, 21.15,
21.03, 20.90, 20.60, 20.60 (6 C, 6 CH3COO),
14.44 (2 C, 2 CH3 alkyl chains). Anal. Calcd
for C54H95NO17 (1030.31): C, 62.95; H, 9.29;
N 1.36. Found; C, 62.78; H, 9.56; N, 1.51.
1-O-(2,3,4,6-Tetra-O-benzoyl-i-
topyranosyl) - 5,6 - di - O - tetradecyl -
D
-galac-
D
- glucitol
(19).—Palladium hydroxide (0.100 g) was
added to a solution of the galactoside 18
(0.635 g, 0.51 mmol) in EtOH (8 mL) and
freshly distilled cyclohexene (4 mL) and the
suspension was stirred for 8 h at 80 °C. After
filtration over celite, the solution was concen-
trated and the residue was purified on a short
column of silica-gel (2:1 petroleum ether–
EtOAc) to provide the pure galactoside 19
(0.524 g, 89%) as an oil. [h]D +55.6° (c 1.0,
CHCl3); Rf 0.50 (2:1 petroleum ether–EtOAc;
1H NMR (CDCl3): l 8.12–7.18 (m, 20 H, 4
C6H5), 6.01 (dd, 1 H, J3%,4% 3.4, J4%,5% 0.6 Hz,
H-4%), 5.82 (dd, 1 H, J1%,2% 7.8, J2%,3% 10.4 Hz,
H-2%), 5.62 (dd, 1 H, H-3%), 4.91 (d, 1 H, H-1%),
4.63 (dd, 1 H, J5%,6%a 7.3, J6%a,6%b 11.4 Hz, H-6%a),
4.61 (dd, 1 H, J5%,6%b 6.0 Hz, H-6%b), 4.39 (ddd,
1 H, H-5%), 3.99 (m, 2 H, H-1a, H-1b), 3.80–
3.41 (m, 12 H, H-2, H-3, H-4, H-5, H-6a,
H-6b, 2 OH, 2 OCH2), 2.98 (d, 1 H, J 6.7 Hz,
OH), 1.52 (m, 4 H, 2 OCH2CH2), 1.26 (m, 44
H, 22 CH2 alkyl chains), 0.88 (t, 6 H, 2 CH3
alkyl chains); 13C NMR (CDCl3): l 166.05,
165.58, 165.55, 165.46 (4 C, 4 C6H5COO),
133.65-133.34, 130.08–128.32 (24 C, 4 C6H5),
102.51 (C-1%), 78.58 (C-5), 73.56, 73.29 (C-2,
C-4), 73.19 (C-1), 71.90 (OCH2), 71.75 (C-3%,
C-5%), 71.27 (OCH2), 70.57 (C-6), 69.93 (C-2%),
68.84 (C-3), 68.24 (C-4%), 62.33 (C-6%), 30.09–
29.45, 26.15, 26.12, 22.75 (CH2 alkyl chains),
14.19 (2 C, 2 CH3 alkyl chains). Anal. Calcd
for C68H96NO15 (1153.43): C, 70.80; H, 8.39.
Found; C, 70.56; H, 8.47.
1-O-(2,3,4,6-Tetra-O-benzoyl-i-
pyranosyl)-3-O-benzyl-5,6-di-O-tetradecyl-
glucitol (18).—To a suspension of 2,3,4,6-
D
-galacto-
D-
tetra - O - benzoyl - a -
D
- galactopyranosyl tri-
chloroacetimidate (17)17 (0.700 g, 0.94 mmol),
alcohol 4 (0.780 g, 1.18 mmol) and crushed
,
activated 4 A molecular sieves in CH2Cl2 (10
mL) at 0 °C, was added in 1 h a solution of
Me3SiOTf (15 mL) in CH2Cl2 (0.5 mL). The
mixture was stirred overnight, then neutral-
ized with triethylamine (20 mL), diluted with
CH2Cl2 (50 mL) and filtrated over celite. After
concentration, the residue was purified by
column chromatography (5:3 petroleum
ether–EtOAc) to afford the pure galactoside
18 (0.660 g, 57%) as an oil. [h]D +51.6° (c
1.0, CHCl3); Rf 0.55 (2:1 petroleum ether–
1
EtOAc); H NMR (CDCl3): l 8.12–7.18 (m,
25 H, 5 C6H5), 6.02 (dd, 1 H, J3%,4% 3.4, J4%,5% 0.5
Hz, H-4%), 5.84 (dd, 1 H, J1%,2% 7.9, J2%,3% 10.4
Hz, H-2%), 5.63 (dd, 1 H, H-3%), 4.87 (d, 1 H,
H-1%), 4.62 (dd, 1 H, J5%,6%a 7.2, J6%a,6%b 11.4 Hz,
H-6%a), 4.60 and 4.54 (2 d, 2 H, J 11.0 Hz,
CH2C6H5), 4.53 (dd, 1 H, J5%,6%b 6.0 Hz, H-6%b),
4.37 (ddd, 1 H, H-5%), 4.14 (m, 1 H, H-2), 4.00
(bd, 1 H, J1a,2 7.0, J1a,1b 10.9 Hz, H-1a), 3.97
(dd, 1 H, J1b,2 5.0 Hz, H-1b), 3.85 (m, 1 H,
H-4), 3.83 (m, 1 H, H-3), 3.68 (dd, 1 H, J5,6a
4.0, J6a,6b 10.2 Hz, H-6a), 3.61 (dq, 1 H, 0.5
OCH2), 3.59 (dd, 1 H, J5,6b 4.7 Hz, H-6b),
3.49–3.40 (m, 4 H, H-5, OH, OCH2), 3.39
(dq, 1 H, 0.5 OCH2), 2.93 (d, 1 H, J4,OH 6.3
1-O-(2,3,4,6-Tetra-O-acetyl-i-
D
-galacto-
pyranosyl)-2,3,4-tri-O-acetyl-5,6-di-O-tetra-

D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
115
(0.955 g, 80%) as an oil. [h]D +54.3° (c 1.0,
decyl- -glucitol (20).—The glycoside 19
D
1
CHCl3); Rf 0.64; H NMR (CDCl3): l 8.12–
(0.440 g, 0.50 mmol) was treated overnight in
MeOH (30 mL) containing a catalytic amount
of MeONa. After concentration, the residue
was acetylated for 16 h at rt in a 2:1 pyridine–
Ac2O mixture (40 mL). After a new concen-
tration, the crude product was purified by
column chromatography (2:1 petroleum
ether–EtOAc) to afford the pure peracety-
lated glycoside 20 (0.360 g, 92%) as an oil.
7.21 (m, 20 H, 4 C6H5), 6.01 (dd, 1 H, J3%,4% 3.3,
J4%,5% 0.7 Hz, H-4%), 5.85 (dd, 1 H, J1%,2% 7.9, J2%,3%
10.3 Hz, H-2%), 5.62 (dd, 1 H, H-3%), 4.98 (d, 1
H, H-1%), 4.70 (dd, 1 H, J5%,6%a 5.9, J6%a,6%b 10.6
Hz, H-6%a), 4.44 (dd, 1 H, J5%,6%b 6.8 Hz, H-6%b),
4.35 (ddd, 1 H, H-5%), 4.24 (bd, 1 H, J1a,2 0.8,
J1a,1b 10.3 Hz, H-1a), 3.88–3.15 (m, 12 H,
H-1b, H-2, H-3, H-4, H-5, H-6a, H-6b, 1 OH,
2 OCH2), 1.54 (m, 4 H, 2 OCH2CH2), 1.26 (m,
50 H, C(CH3)2, 22 CH2 alkyl chains), 0.88 (t,
1
[h]D −6.8° (c 1.0, CHCl3); Rf 0.58; H NMR
(CDCl3): l 5.46 (dd, 1 H, J2,3 5.0, J3,4 5.7 Hz,
H-3), 5.40 (dd, 1 H, J3%,4% 3.4, J4%,5% 0.7 Hz,
H-4%), 5.23 (m, 1 H, H-4), 5.22 (ddd, 1 H, J1a,2
7.0, J1b,2 3.9 Hz, H-2), 5.17 (dd, 1 H, J1%,2% 7.9,
J2%,3% 10.4 Hz, H-2%), 5.02 (dd, 1 H, H-3%), 4.47
(d, 1 H, H-1%), 4.17 (d, 2 H, J 6.9 Hz, H-6%a,
H-6%b), 3.93 (dd, 1 H, J1a,1b 11.5 Hz, H-1a),
3.91 (ddd, 1 H, H-5%), 3.71 (dd, 1 H, H-1b),
3.58-3.38 (m, H-5, H-6a, H-6b, 2 OCH2), 2.17,
2.11, 2.11, 2.09, 2.07, 2.07, 1.99 (7s, 21 H, 7
CH3CO), 1.55 (m, 4 H, 2 OCH2CH2), 1.29 (m,
44 H, 22 CH2 alkyl chains), 0.89 (t, 6 H, 2
CH3 alkyl chains); 13C NMR (CDCl3): l
170.10, 170.04, 169.85, 169.61, 169.73, 169.45,
169.30 (7 C, 7 CH3COO), 100.92 (C-1%), 76.53
(C-5), 71.59 (OCH2), 70.79 (C-6), 70.64 (C-3%),
70.20 (C-5%), 70.16 (C-2, C-4), 69.66 (OCH2),
69.11 (C-3), 68.42 (C-2%), 67.15 (C-1), 66.96
(C-4%), 61.05 (C-6%), 31.85, 29.75, 29.60, 29.50,
29.41, 29.37, 29.27, 26.03, 25.91, 22.58 (CH2
alkyl chains), 20.67, 20.65, 20.60, 20.47, 20.47,
20.47, 20.37 (7 C, 7 CH3COO), 14.00 (2 C, 2
CH3 alkyl chains). Anal. Calcd for C54H94O18
(1031.29): C, 62.88; H, 9.19. Found; C, 62.93;
H, 9.37.
13
6 H, 2 CH3 alkyl chains); C NMR (CDCl3):
l 166.05, 165.61, 165.61, 165.19 (4 C, 4
C6H5COO), 133.56–133.26, 129.84–128.29
(24 C, 4 C6H5), 109.39 (C(CH3)2), 102.34 (C-
1%), 80.11 (C-5), 78.80 (2 C, C-3, C-4), 72.76
(C-2), 71.90 (C-3%), 71.76, 71.63 (2 C, C-1,
OCH2), 71.32 (C-5%), 71.23 (OCH2), 70.84 (C-
6), 70.06 (C-2%), 68.20 (C-4%), 62.02 (C-6%),
31.98, 29.77-29.42 (CH2 alkyl chains), 26.84 (2
C, C(CH3)2), 26.21-25.89, 22.74 (CH2 alkyl
chains), 14.18 (2 C, 2 CH3 alkyl chains). Anal.
Calcd for C71H100NO15 (1193.51): C, 71.44; H,
8.44. Found; C, 71.28; H, 8.47.
1-O-(2,3,4,6-Tetra-O-benzoyl-i-
pyranosyl) - 5,6 - di - O - tetradecyl -
D
-galacto-
D
- mannitol
(22).—A solution of the pure glycoside 21
(0.478 g, 0.40 mmol) in 80% aq AcOH was
heated for 14 h at 90 °C. After concentration
and coevaporation from toluene (2×10 mL),
the residue was purified on a short column of
silica-gel (5:4 petroleum ether–EtOAc) to af-
ford the pure glycoside 22 (0.410 g, 89%) as an
oil. [h]D +48.9° (c 1.0, CHCl3); Rf 0.35 (2:1
1
petroleum ether–EtOAc); H NMR (CDCl3):
1-O-(2,3,4,6-Tetra-O-benzoyl-i-
pyranosyl) - 3,4 - O - isopropylidene - 5,6 - di - O-
tetradecyl- -mannitol (21).—To a suspension
of
D
-galacto-
l 8.13–7.26 (m, 20 H, 4 C6H5), 6.02 (dd, 1 H,
J3%,4% 3.4, J4%,5% 0.6 Hz, H-4%), 5.82 (dd, 1 H, J1%,2%
7.8, J2%,3% 10.5 Hz, H-2%), 5.65 (dd, 1 H, H-3%),
4.94 (d, 1 H, H-1%), 4.67 (dd, 1 H, J5%,6%a 6.6,
J6%a,6%b 11.4 Hz, H-6%a), 4.48 (dd, 1 H, J5%,6%b 6.4
Hz, H-6%b), 4.38 (ddd, 1 H, H-5%), 4.22 (bd, 1
H, J1a,2 2.4, J1a,1b 10.0 Hz, H-1a), 3.94–3.89
(m, 2 H, H-2, H-4), 3.87 (dd, 1 H, J1b,2 6.6 Hz,
H-1b), 3.67 (ddd, 1 H, J2,3 6.3, J3,4 2.4, J3,OH
6.0 Hz, H-3), 3.59 (dq, 1 H, 0.5 OCH2),
3.55–3.50 (m, 3 H, H-5, H-6a, H-6b), 3.46
(dq, 1 H, 0.5 OCH2), 3.42 (dq, 2 H, 1 OCH2),
3.16 (d, 1 H, J 5.7 Hz, OH), 3.14 (d, 1 H, J
6.3 Hz, OH), 2.78 (d, 1 H, J 6.0 Hz, OH),
1.54 (m, 4 H, 2 OCH2CH2), 1.27 (m, 44 H, 22
D
2,3,4,6-tetra-O-benzoyl-a- -galactopyra-
D
nosyl trichloroacetimidate (17)17 (741 mg, 1.00
mmol), alcohol 10 (0.615 g, 1.00 mmol) and
,
crushed activated 4 A molecular sieves in
CH2Cl2 (5 mL) at 0 °C, was added in 1 h a
solution of Me3SiOTf (10 mL) in CH2Cl2 (0.5
mL). The mixture was stirred overnight, then
neutralized with triethylamine (20 mL), diluted
with CH2Cl2 (50 mL) and filtrated over celite.
After concentration, the residue was purified
by column chromatography (3:1 petroleum
ether–EtOAc) to afford the pure glycoside 21

116
D. Lafont et al. / Carbohydrate Research 331 (2001) 107–117
for C54H94O18 (1031.29): C, 62.88; H, 9.19.
Found; C, 62.58; H, 9.20.
CH2 alkyl chains), 0.90 (t, 6 H, 2 CH3 alkyl
chains); 13C NMR (CDCl3): l 166.02, 165.60,
165.53, 165.53 (4 C, 4 C6H5COO), 133.56–
133.25, 130.50–128.28 (24 C, 4 C6H5), 102.22
(C-1%), 79.96 (C-5), 72.46 (C-1), 71.84 (OCH2),
71.75 (C-3%), 71.56 (C-5%), 71.36 (OCH2), 70.82
(C-6), 70.77 (C-2), 70.50 (C-3), 70.13 (C-2%,
C-4), 68.34 (C-4%), 62.20 (C-6%), 31.97, 30.11–
29.41, 26.14, 22.73 (CH2 alkyl chains), 14.17
(2 C, 2 CH3 alkyl chains). Anal. Calcd for
C68H96NO15 (1153.44): C, 70.80; H, 8.39.
Found; C, 70.64; H, 8.45.
1-O-(2-Acetamido-2-deoxy-i-
nosyl)-5,6-di-O-tetradecyl- -glucitol (24).—
D
-glucopyra-
D
Compound 14 (0.402 g, 0.39 mmol) in MeOH
(15 mL) was stirred for 24 h in the presence of
a catalytic amount of MeONa. The solubiliza-
tion occurred after a few minutes, and the
deacetylated product started to crystallize
some minutes later. The product 24 (0.175 g,
90%) was obtained by filtration and washed
with MeOH (3×5 mL): solid, mp 193 °C
(MeOH). Anal. Calcd for C42H83NO11
(778.09): C, 64.83; H, 10.75; N 1.80. Found;
C, 64.76; H, 11.13; N, 1.92.
1-O-(2,3,4,6-Tetra-O-acetyl-i-
pyranosyl)-2,3,4-tri-O-acetyl-5,6-di-O-tetra-
decyl- -mannitol (23).—The glycoside 22
D
-galacto-
D
1-O-(2-Acetamido-2-deoxy-i-
osyl)-5,6-di-O-tetradecyl- -mannitol (25).—
D
-glucopyran-
(0.577 g, 0.50 mmol) was treated overnight in
MeOH (30 mL) containing a catalytic amount
of MeONa. After concentration, the residue
was acetylated for 16 h at rt in a 2:1 pyridine–
Ac2O mixture (40 mL). After a new concen-
tration, the residue was purified by column
chromatography (2:1 petroleum ether–
EtOAc) to afford the pure peracetylated gly-
coside 23 (0.480 g, 93%) as a solid. Mp 60 °C
(EtOH); [h]D +42.5° (c 1.0, CHCl3); Rf 0.58;
1H NMR (CDCl3): l 5.47 (dd, 1 H, J2,3 8.4,
J3,4 2.3 Hz, H-3), 5.39 (dd, 1 H, J3%,4% 3.4, J4%,5%
0.8 Hz, H-4%), 5.20 (dd, 1 H, J1%,2% 7.9, J2%,3% 10.4
Hz, H-2%), 5.18 (dd, 1 H, J4,5 7.8 Hz, H-4),
5.14 (ddd, 1 H, J1a,2 3.2, J1b,2 6.7 Hz, H-2),
5.00 (dd, 1 H, H-3%), 4.48 (d, 1 H, H-1%), 4.18
(dd, 1 H, J5%,6%a 6.6, J6%a,6%b 11.2 Hz, H-6%a), 4.13
(dd, 1 H, J5%,6%b 6.9 Hz, H-6%b), 3.99 (dd, 1 H,
J1a,1b 11.3 Hz, H-1a), 3.90 (ddd, 1 H, H-5%),
3.60 (dq, 1 H, 0.5 OCH2), 3.57 (dd, 1 H,
H-1b), 3.50 (dd, 1 H, J5,6a 3.5, J6a,6b 9.8 Hz,
H-6a), 3.44 (m, 1 H, H-5), 3.43–3.36 (m, 3 H,
H-6b, OCH2), 3.31 (dq, 1 H, 0.5 OCH2), 2.16,
2.14, 2.09, 2.08, 2.07, 2.05, 1.99 (7s, 21 H, 7
CH3COO), 1.53 (m, 4 H, 2 OCH2CH2), 1.27
(m, 44 H, 22 CH2 alkyl chains), 0.90 (t, 6 H,
2 CH3 alkyl chains); 13C NMR (CDCl3): l
170.10, 170.02, 169.85, 169.85, 169.68, 169.68,
169.68 (7 C, 7 CH3COO), 100.91 (C-1%), 76.35
(C-5), 71.58, 71.13 (2 C, 2 OCH2), 70.80 (C-
3%), 70.63 (C-5%), 70.46 (C-6), 69.46 (C-4),
69.14 (C-2), 68.98 (C-3), 68.40 (C-2%), 67.48
(C-1), 66.97 (C-4%), 62.10 (C-6%), 31.82, 29.83–
29.26, 26.01, 25.90, 22.57 (CH2 alkyl chains),
13.99 (2 C, 2 CH3 alkyl chains). Anal. Calcd
D
Compound 16 (0.360 g, 0.35 mmol) in MeOH
(15 mL) was treated as described for 14. The
product 25 was recovered as a solid (0.253 g,
93%); mp 191 °C (MeOH). Anal. Calcd for
C42H83NO11·H2O (796.11): C, 63.36; H, 10.76;
N 1.76. Found; C, 63.17; H, 10.61; N, 1.86.
1-O-i-
D
-Galactopyranosyl-5,6-di-O-tetra-
decyl- -glucitol (26).—The glycoside 20
D
(0.300 g, 0.29 mmol) was treated overnight in
MeOH (10 mL) containing a catalytic amount
of sodium methylate. After neutralization with
an Amberlyst IR 120 (H+) resin, the solution
was concentrated to afford a solid which was
just washed with deionized water, recovered
by filtration and crystallized from abs EtOH
(0.195 g, 89% yield). Mp 192 °C (EtOH).
Anal. Calcd. for C40H80O11·H2O (755.06): C,
63.62; H, 10.95. Found; C, 63.47; H, 10.85.
1-O-i-
D
-Galactopyranosyl-5,6-di-O-tetra-
decyl- -mannitol (27).—The glycoside 23
D
(0.343 g, 0.42 mmol) was treated as described
for 16 to afford 27 as a solid (0.291 g, 92%
yield). Mp 199 °C (MeOH). Anal. Calcd. for
C40H80O11·H2O (755.06): C, 63.62; H, 10.95.
Found; C, 63.47; H, 10.84.
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