Synthesis and interfacial properties of amphiphilic β-cyclodextrins and their substitution at the O-6 position with a mono bio-recognisable galactosyl antenna

Article abstract of DOI:10.1016/j.tet.2005.06.054

The synthesis of a mono-galactosylated amphiphilic β-cyclodextrin, in five steps from mono-6-azido-6-deoxy-β-cyclodextrin, via coupling to a N-β-d-galactopyranosylamino-antenna is described. Both characterization by electrospray mass spectrometry and NMR show the presence of only the mono-substituted product. The Langmuir isotherms of the final product and intermediates are described.

Full text of DOI:10.1016/j.tet.2005.06.054

Tetrahedron 61 (2005) 8740–8745
Synthesis and interfacial properties of amphiphilic
b-cyclodextrins and their substitution at the O-6 position with a
mono bio-recognisable galactosyl antenna
a
Alain Salameh, Adina N. Lazar, Anthony W. Coleman and Helene Parrot-Lopez
b
b
a,
*
´ `
a
´ ` ´ ´
Methodologie de Synthese et Molecules Bioactives, UMR-CNRS 5181, Universite Claude Bernard-Lyon 1,
ˆ
Domaine Scientifique de la Doua, Bat. J. Raulin, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne cedex, France
´
Institut de Biologie et Chimie des Proteines, CNRS-UMR 5086, 7 passage du Vercors, Lyon cedex 07, 69367, France
b
Received 8 April 2005; revised 9 June 2005; accepted 16 June 2005
Abstract—The synthesis of a mono-galactosylated amphiphilic b-cyclodextrin, in five steps from mono-6-azido-6-deoxy-b-cyclodextrin,
via coupling to a N-b-D-galactopyranosylamino-antenna is described. Both characterization by electrospray mass spectrometry and NMR
show the presence of only the mono-substituted product. The Langmuir isotherms of the final product and intermediates are described.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
Indeed to pass from a system of 1:1 complexation to
nanoparticles able to ensure a much higher degree of
encapsulation, the use of amphiphilic cyclodextrins has
been developed. In the previous studies, amphiphilic
cyclodextrins were obtained by the introduction of
lipophilic groups at the primary face and/or secondary
face.8 These amphiphilic cyclodextrins are capable of
forming liposomes,9 nanoparticles,10 vesicles,11 micellar
aggregates 12 and solid lipid nanoparticles.13
b-Cyclodextrins (b-CDs) or cyclomaltoheptaoses have long
been recognized to have significant potential as drug carriers
arising from their ability to form inclusion complexes.1
Inclusion of the bioactive molecules generates several
therapeutic advantages: solubilisation of poorly soluble or
insoluble molecules,2 protection from chemical and
enzymatic degradation,3 transport and time control of
release.4 Currently, in order to reduce the appearance of
resistance towards therapeutic agents and to decrease the
toxicity of the bioactive molecules, several studies have
been undertaken to target such carriers, reducing in this way
the quantity of drug used in therapies. Carbohydrates are
biocompatible molecules having low immunogenicity and
are responsible of recognition between the cells. We have
previously demonstrated the capacity of galactosyl-b-
cyclodextrin to be recognized by a galactosyl specific cell
wall lectin Kluyveromyces bulgaricus (KbCWL)5 and in the
literature there exist several reports of the synthesis of
cyclodextrin derivatives substituted with mono or poly-
saccharides and which have shown to be recognized by
lectins.6 Recently, chemo-enzymatic synthesis of amphi-
philic cyclodextrins fully substituted with N-acetyl-gluco-
The objective of the current work resides in the combination
of the recognition properties of the mono-galactosyl-b-
cyclodextrins and their amphiphilic properties to obtain new
carrier molecules containing a galactosyl antenna at the O-6
position and lipophilic ester groups at the O-2 and O-3
positions. The synthesis, characterization and the interfacial
properties of these molecules as Langmuir monolayers are
described.
2. Results and discussion
2.1. Synthesis and characterization
7
samine (Glc-NAc) has been described.
In previous studies we have demonstrated good recognition
capacity (1.75 mmol dmK3) towards a galactose specific
yeast lectin K. bulgaricus (Kb CWL) of a mono-galactosyl-
b-CD derived from mono-6-amino-6-deoxy-b-CD by
coupling a galactosyl head group via a spacer chain (9
carbon atoms). In contrast to expectations, a ‘clustering
Keywords: Amphiphilic cyclodextrin; Galactosyl antenna; Langmuir
isotherms.
Corresponding author. Tel.: C33 472431532; fax: C33 472448438;
e-mail: h.parrot@cdlyon.univ-lyon1.fr
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.06.054

A. Salameh et al. / Tetrahedron 61 (2005) 8740–8745
8741
effect’ by the heptakis-galactosyl-b-CD was not observed
The degree of substitution is easily verified by electrospray
mass-spectrometry (ES-MS, positive mode, m/z: 1621.4
with only a 1.5 fold increase in recognition.5
[MCHCNa]2C and the structure confirmed by 1H and 13
NMR spectroscopy.
C
In view of the above, the mono-galactosylated amphiphilic
b-cyclodextrin derivative 7 was synthesized from mono-6-
azido-6-deoxy-b-cyclodextrin 114 in five steps (Scheme 1).
The synthetic procedure for the synthesis of 7 is based on an
amide bond between the carbohydrate-antenna and the
amphiphilic-b-cyclodextrin moiety.
Selective removal of the tert-butyldimethylsilyl groups at
O-6 position of 3 by boron trifluoride etherate (BF3$Et2O) in
dry CHCl3 gave the new product 4 with one azido group on
the primary face and 14 hexanoyl chains on the secondary
hydroxyl groups in 97% yield.
O-acylation at the secondary hydroxyl groups of the b-CD
requires protection of the free primary hydroxyl groups at
O-6 position of mono-6-azido-6-deoxy-b-cyclodextrin 1
with tert-butyldimethylsilyl chloride in dry pyridine. The
new intermediate 2 is recrystallized from chloroform (yield
86%). The use of 56 equiv of hexanoic anhydride and
42 equiv of 4-dimethylaminopyridine (DMAP) leads to the
pure fully acylated product 3 with 14 hexanoyl chains at
secondary face of the b-cyclodextrin, according to the
conditions of Lesieur and Dubes.15 We have applied a new
method of purification consisting of simply precipitating 3
from a mixture of methanol/chloroform 95:5 in 66.7% yield.
The reduction of the azido group into the corresponding
amino group is carried out by catalytic hydrogenation. The
presence of the ester groups at the secondary face requires
neutral condition; here the use of Staudinger reduction is not
successful. The novel mono-6-amino-6-deoxy-amphiphilic
cyclodextrin 5 was synthesized from 4 in MeOH in presence
of the Pd/C (10%) under hydrogen pressure (2 bar) during
4 h in 95% yield. The absence of the azido band at
2100 cmK1 was confirmed by IR spectroscopy.
The covalent amido linkage between the glycoconjugate
Scheme 1. Synthesis of galactosylated amphiphilic cyclodextrin: (i) TBDMSCl, pyridine; (ii) hexanoic anhydride, DMAP, pyridine; (iii) BF3$Et2O CHCl3;
(iv) Pd/C, H2, MeOH; (v) 6, DCC, HOBT, DMF.

8742
A. Salameh et al. / Tetrahedron 61 (2005) 8740–8745
Scheme 2. Synthesis of the glycoconjugate 6. (i) KSCN, Bu4NCBrK, Acetonitrile; (ii) Et3N, toluene; (iii) NaOH (1 M), MeOH.
Figure 1. ES-mass spectrometry of the mono-galactosylated amphiphilic b-cyclodextrin 7.
1
1
1
Figure 2. (A) H–13C 2D HMBC NMR spectrum of 7; (B) H NMR spectrum of galactose from 2D TOCSY; (C) H NMR spectrum of glucopyranose A
substituted by galactosyl antenna from 2D TOCSY.

A. Salameh et al. / Tetrahedron 61 (2005) 8740–8745
8743
and b-CD requires the synthesis of amphiphilic synthons
presenting an amine function at the primary face and
terminal carboxylic acid function in the glycoconjugate. We
HMBC, TOCSY) at 500 MHz in pyridine-d5. The 13C–1H
HMBC NMR spectrum (Fig. 2A) clearly shows the
correlation between the amide proton of the galactosyl
residue at 9.55 ppm and the C]O carbon at 174.2 ppm; also
a correlation is observed between the amide proton of the
substituted glucopyranose A of b-cyclodextrin at 8.44 ppm
and the carbonyl carbon at 174.1 ppm. Covalent coupling is
confirmed by the presence of a correlation between the
amide C]O of the b-cyclodextrin and the CH2 (a to the
have described the synthesis of 9-(N-b-D-galactopyranosyl-
¨
16
amino)azelaıc acid 6 from tetra-O-acetyl-a-D-bromo-
galactose in three steps via galactosylisothiocyanate
(Scheme 2).
The method used to synthesize the final product 7, is that of
a peptide coupling under soft conditions, in the presence of
dicyclohexylcarbodiimide (DCC) and hydroxybenzotria-
zole (HOBT) in the anhydrous DMF. This method appeared
to us most judicious to graft via a covalent bond an
unprotected b-D-galactose onto the amphiphilic b-CD
derivative. This method avoids working at high temperature
in the presence of the galactosylated antenna. Mono-
galactosyl amphiphilic-b-cyclodextrin 7 was synthesized
by condensation of glycoconjugate 6 with mono-6-amino-6-
deoxy-amphiphilic-b-cyclodextrin 5 in dry DMF using
DCC/HOBT as the coupling reagents. The product was
isolated by chromatography on silica gel with EtOH/toluene
8:2 as eluent in 42% yield. Characterization by mass
spectrometry of 7 showed only species corresponding to
[7C2Na]2C: (m/z: 1442.5) and [7C Na]C: (m/z: 2861.3)
(Fig. 1). This substitution by one galactosyl antennae at the
O-6 position and 14 hexanoyl chains at O-2 and O-3
positions were confirmed by 2D 1H and 13C NMR (COSY,
1
C]O) of galactosyl antenna situated at 2.36 ppm. H–1H
TOCSY has allowed attribution of the protons arising from
the galactose (Fig. 2B) and those of glucopyranose A, which
are displaced by the substitution (Fig. 2C).The presence of a
series of doublets between 5.3 and 5.0 ppm characteristic of
the anomeric protons demonstrates the loss of symmetry of
the molecule and confirms the monosubstitution at the
primary face the b-cyclodextrin molecule.
No interaction is observed between the galactosyl antennae
and the H-3 and H-5 protons of b-cyclodextrin. The terminal
hydrophilic group of the antennae makes it possible to avoid
the well-known phenomenon in the literature of self-
inclusion of chains alkyls of the monosubstituted b-CD.17
2.2. Interfacial properties
Langmuir compression isotherms were obtained for
Figure 3. Langmuir isotherms of amphiphilic cyclodextrin derivatives: (a) 4; (b) 5; (c) 7 and (d) 8.

8744
A. Salameh et al. / Tetrahedron 61 (2005) 8740–8745
Table 1. Apparent molecular areas, collapse pressures and compressibility of amphiphilic cyclodextrins Langmuir films
2
2
2
˚
˚
˚
Amphiphilic cyclo-
dextrin
A0 hA i
A1 hA i
Ac hA i
Pc hmN/mi
Cs
Compound 4
Compound 5
Compound 7
Compound 8
373 (G3)
395 (G3)
410 (G3)
360 (G3)
366 (G3)
378 (G3)
390 (G3)
350 (G3)
214 (G2)
220 (G2)
250 (G2)
209 (G2)
36.6 (G0.2)
41.3 (G0.2)
42 (G0.2)
41 (G0.2)
55.8 (G1)
59 (G1)
62 (G1)
59 (G1)
A0, apparent molecular area at pZ0.1 mN/m; A1, apparent molecular area for pressureZ1 mN/m; Ac, apparent molecular area at collapse; Pc, pressure at
collapse; CsZcompressibility.
compounds 4, 5 and 7 and are given along with that of the
parent compound tetradecakis-O2, O3-hexanoyl-b-cyclo-
dextrin 8, Figure 3a–d, respectively. The relevant isotherm
data is summarized in Table 1.
allowed to equilibrate during 30 min to compression.
Compressions were performed continuously at a rate of
20 cm2 minK1 from 510 to 50 cm2. Each isotherm was run
at least three times to ensure areas of reproducibility of
results (deviation of area and pressure were less than 3%).
Molecules 4, 5 and 8 show collapse areas in the range 205–
2
˚
220 A , in close agreement with values previously observed
4.1.1. Mono-6-azido-6-deoxy-hexakis(6-O-tert-butyl-
dimethylsilyl)cyclomaltoheptaose 2. Mono-6-azido-6-
deoxy-b-cyclodextrin 1 (5.5 g, 4.74 mmol) in dry pyridine
(80 mL) is added a solution of tert-butyldimethylsilyl
chloride (TBDMSCl) (6.43 g, 42.6 mmol) in 70 mL of dry
pyridine at 0 8C. After agitation during 3 h at 0 8C and 20 h
at 20 8C, the reaction is stopped by addition of ice (500 g).
The crude product precipitated, filtered and recrystallised in
water; 86% yield; mp 225 8C; [a]DZC13.4 (c 1); 1H NMR
(CDCl3, 300 MHz): d (ppm): 6.55–6.82 (m, 7H, OH), 5.18–
5.3 (m, 7H, OH), 4.87 (d, 1H, JZ3.8 Hz, H-1), 4.96 (d, 6H,
JZ3.8 Hz, H-1), 4.05–3.6 (m, 42H, H-2, H-3, H-4, H-5,
H-6), 0.88 (s, 54H, CH3–C), 0.04 (s, 36H, CH3–Si); 13C
NMR (CDCl3, 75 MHz): d (ppm)K4.79 (C–Si), 18.68 (C–
(CH3)3), 26.28 (C–(CH3)3), 52.51 (C6–N3), 62.77 (C6–Si),
72.63 (C3), 72.94 (C2), 73.91 (C5), 82.16 (C4), 102.32 (C1);
ES-MS (C) m/z: 1867.7 [MCNa]C; C78H153N3O34Si6.
for similar compounds by Lesieur15a. This lack of
significant variance in the collapse area is in agreement
with the fact that the molecular size of cyclodextrins
acylated at the secondary face is determined by the area
contribution from the 14 acyl chains18, and not the
cyclodextrin core. However, in the case of 7, the presence
2
˚
of the galactosyl antenna leads to a collapse area of 250 A .
The collapse pressures show a variation 7O5R8O4, as
would be expected from differences in the head group
hydrophilicity, where introduction of a charged amino
group 5 and especially the carbohydrate antenna 7 increases
film stability, while introduction of an apolar, non-hydrogen
bonding, azido function in 4 markedly decreases film
stability.
3. Conclusion
4.1.2. Mono-6-azido-6-deoxy-hexakis(6-O-tert-butyl-
dimethylsilyl)-heptakis(2,3-di-O-hexanoyl)-cyclomalto-
heptaose 3. The use of 56 equiv of hexanoic anhydride
(71.7 mmol, 16.6 mL), 42 equiv of 4-dimethylamino-
pyridine (DMAP) (6.57 g, 53.7 mmol) in dry pyridine
(40 mL) and 2.36 g (1.28 mmol) of 2 leads to the fully
acylated product 3. The mixture was stirred under nitrogen
pressure at 70 8C for 48 h, then cooled at 25 8C and poured
thereafter in 250 mL of distilled water. The organic layer
was dried with Na2SO4 and concentrated to dryness to yield
oil. The MeOH/CH2Cl2 95:5 solution is added in oil and the
mixture is heated at 70 8C. The product 3 precipitate. 66.7%
yield (2.75 g); mp 205 8C; [a]D 15.3 (c 1); 1H NMR (CDCl3,
300 MHz): d (ppm): 5.5–5.3 (m, 7H, H-3), 5.2–5.05 (m, 7H,
H-1), 4.85–4.59 (m, 7H, H-2), 3.6–4.02 (m, 28H, H-4, H-5,
H-6), 2.55–2.1 (m, 28H, CH2–COO), 1.15 (s, 56H, –CH2–
CH2–CH2–COO), 1.8 (s, 28H, CH3–CH2–), 1.05–0.75 [m,
96H, CH3 and C–(CH3)3], 0.04 (s, 36H, CH3–Si); 13C NMR
(CDCl3, 75 MHz): d (ppm): K4.6 (C–Si), 14.3 (CH3), 18.6
(C–(CH3)3, 22.7 (–CH2–CH3), 24.8 (–CH2–CH2–CH3), 26.3
(C–(CH3)3), 31.9 (–CH2–CH2–COO), 34.5 (–CH2–COO),
52.1 (C6–N3), 62.1 (C6–Si), 70.0–72.2 (C2 and C3), 72.4
(C5), 77.7 (C4), 96.7 (C1), 172.1 (–CH2–COO), 174.2
We have synthesized a new generation of cyclodextrins
presenting a galactosylated antenna on the primary face of
b-cyclodextrin and O-acyls groups on the secondary face.
These cyclodextrins are characterised by NMR and mass
spectroscopy. The Langmuir isotherms show the amphi-
philic character of these new molecules, and work is
underway to study the self-assembly and transport proper-
ties of these molecules.
4. Experimental
4.1. General
All chemicals were purchased from Aldrich and were used
without further purification. b-cyclodextrin was generously
provided by Wacker (Lyon, France) and was dried under
vacuum (10K2 T) at 120 8C for 48 h before use. 1H and 13
C
NMR experiments were performed at 300 and 75 MHz,
respectively, using a Bruker DRX 300 spectrometer. 2D
Experiments (COSY, TOCSY, HMBC) were recorded with
a Bruker AM 500 spectrometer. Mass spectra were
measured using a Perkin-Elmer Sciex spectrometer. IR
spectra were recorded on a Perkin-Elmer instrument.
Isotherms were carried out on a Langmuir type balance
(Nima 610) using MilliQ water (resistivity O18 MU) as the
subphase. Solutions of the molecules in CHCl3 at suitable
concentrations were deposited on the aqueous surface and
(–CH2–COO); ES-MS (C) m/z: 1621.4 [3CHC Na]2C
1629.9 [3CHCK]2C; C164H293N3O48Si6.
,
4.1.3. Mono-6-azido-6-deoxy-heptakis(2,3-di-O-hexa-
noyl)-cyclomaltoheptaose 4. To a stirred solution of 3
(2.75 g, 0.85 mmol) in anhydrous chloroform stabilized on

A. Salameh et al. / Tetrahedron 61 (2005) 8740–8745
8745
amylene (63 mL) was added 1.7 mL of BF3$Et2O. The
JZ9 Hz, NH-gal); ES-MS (C) m/z: 1442.5 [7C2Na]2C
2861.3 [7CNa]C; C1143H236N2O55.
,
mixture was stirred under N2 at 25 8C for 23 h then poured
into cold water (160 mL). The organic layer was removed
and washed with water, NaHCO3 and water then dried with
Na2SO4. The organic layer was then concentrated to dryness
and the residue purified by flash chromatography (eluent:
cyclohexane/acetone 6:4). 97% Yield; mp 194 8C; [a]D 12.4
References and notes
1
(c 1); H NMR (CDCl3, 300 MHz): d (ppm): 0.9 (s, 42H,
CH3), 1.3 (s, 56H, –CH2–CH2–CH2–COO), 1.6 (s, 28H,
CH3–CH2–), 2.08–2.42 (m, 28H, CH2–COO), 3.55–4.15 (m,
28H, H-4, H-5, H-6), 4.25–4.55 (m, 6H, OH), 4.65–4.8 (m,
7H, H-2), 5.01 (d, 1H, JZ3.8 Hz, H-1), 5.12 (d, 5H, JZ
3.8 Hz, H-1), 5.18 (d, 1H, JZ3.8 Hz, H-1), 5.29–5.45 (m,
7H, H-3); 13C NMR (CDCl3, 75 MHz): d (ppm): 14.30
(CH3), 22.79 (–CH2–CH3), 24.75 (–CH2–CH2–CH3), 31.77
(–CH2–CH2–COO), 34.36 (–CH2–COO), 52.1 (C6–N3),
62.10 (C6), 70.74 (C2), 72.44 (C3), 75.20 (C5), 76.56 (C4),
96.70 (C1), 172.16 (–CH2–COO), 173.72 (–CH2–COO);
ES-MS (C) m/z: 2556.6 [4C Na]C; C128H209N3O48.
1. Uekama, K.; Hirayama, F.; Irie, T. Chem. Rev. 1998, 98,
2045–2076.
ˆ
2. Duchene, D. News Trends in Cyclodextrin and Derivatives;
´
Edition de Sante: Paris, 1991.
3. Szejtli, J. Med. Res. Rev. 1994, 14, 353–386.
4. Szejtli, J. Cyclodextrin Technology; Kluwer Academic:
Dordrecht, 1998.
5. Attioui, F.; Al-Omar, A.; Leray, E.; Parrot-Lopez, H.; Finance,
C.; Bonaly, R. Biol. Cell. 1994, 82, 161–167.
6. Ortiz-Mellet, C.; Defaye, J.; Garcia-Fernandez, J. M. Chem.
Eur. J. 2002, 8, 1982–1990. Furuike, T.; Aiba, S.; Nishimura,
S. I. Tetrahedron 2000, 56, 9909–9915.
4.1.4. Mono-6-amino-6-deoxy-heptakis(2,3-di-O-hexa-
noyl)-cyclomaltoheptaose 5. To a solution of 4 (5 g,
1.97 mmol) in MeOH (200 mL) was added 450 mg of the
Pd/C (10%) under hydrogen pressure (2 bar) at 20 8C for
4 h. The mixture was filtered and washed with MeOH. Yield
95%; mp 175 8C; [a]D 11.6 (c 1); IR (KBr): no band azido at
n 2100 cmK1; 1H NMR (CDCl3, 300 MHz): d (ppm): 0.9 (s,
42H, CH3), 1.3 (s, 56H, –CH2–CH2–CH2–COO), 1.56 (s,
28H, CH3–CH2–), 2.08–2.37 (m, 28H, CH2–COO), 3.4–4.2
(m, 34H, H-4, H-5, H-6, OH-6), 4.7–4.79 (m, 7H, H-2), 5.01
(d, 1H, JZ3.8 Hz, H-1), 5.12 (d, 5H, JZ3.8 Hz, H-1), 5.18
(d, 1H, JZ3.8 Hz, H-1), 5.29–5.45 (m, 7H, H-3); 13C NMR
(CDCl3, 75 MHz): d (ppm): 14.30 (CH3), 22.79 (–CH2–
CH3), 24.75 (–CH2–CH2–CH3), 31.77 (–CH2–CH2–COO),
34.36 (–CH2–COO), 62.10 (C6), 70.69 (C2), 72.42 (C3),
75.20 (C5), 76.56 (C4), 96.70 (C1), 172.16 (–CH2–COO),
173.72 (–CH2–COO); ES-MS (C) m/z: 2531 [5CNa]C;
C128H211NO48.
7. Sallas, F.; Niikura, K.; Nishimura, S. I. Chem. Commun. 2004,
596–597.
8. (a) Tanaka, M.; Azumi, R.; Tachibana, H.; Nakamura, T.;
Kawabata, Y.; Matsumoto, M.; Miyasaka, T.; Tagaki, W.;
Nakahara, H.; Fukuda, K. Thin Solid Films 1994, 244,
832–835. (b) Greenhall, M.; Lukes, P.; Kataky, R.; Agbor,
N. E.; Badyal, J. P.; Yarwood, J.; Parker, D.; Petty, M. C.
Langmuir 1995, 11, 3997–4000. (c) Zhang, P.; Ling, C. C.;
Coleman, A. W.; Parrot-Lopez, H.; Galons, H. Tetrahedron
Lett. 1991, 32, 2769–2770. (d) Mazzaglia, A.; Donohue, R.;
Ravoo, B. J.; Darcy, R. Eur. J. Org. Chem. 2001, 1715–1721.
´
(e) Granger, C.; Felix, C.; Parrot-Lopez, H.; Langlois, B.
Tetrahedron Lett. 2000, 41, 9257–9260. (f) Sukegawa, T.;
Furuike, T.; Niikura, K.; Yamagishi, A.; Monde, K.;
Nishimura, S. I. Chem. Commun. 2002, 430–431. (g) Peroche,
S.; Parrot-Lopez, H. Tetrahedron Lett. 2003, 44, 241–245.
´ ´ ´
9. Auzely-Velty, R.; Perly, B.; Tache, O.; Zemb, T.; Jehan, P.;
¨
Guenot, P.; Dalbiez, J. P.; Djedaıni-Pilard, F. Carbohydrate
Res. 1999, 318, 82–90.
10. Perrier, E.; Terry, N.; Rival, D.; Coleman, A. W. Jpn. Kokai
Tokkyo Koho 2001,323,002, 2001.
4.1.5. Mono-6-deoxy-6[9-(b-D-galactopyranosylamino)-
1,9-dioxononanoyl]amino-heptakis(2,3-di-O-hexanoyl)-
cyclomaltoheptaose 7. To a solution of 5 (0.9 g,
0.36 mmol) in dry DMF (18 mL) were added 616 (1 equiv
0.13 g), hydroxybenzotriazole (HOBT, 1.2 equiv 0.058 g)
and dicyclohexylcarbodiimide (DCC, 1.2 equiv 0.088 g).
The mixture is then left under agitation at 25 8C, until
appearance of a fine precipitate corresponding to the
formation of dicyclohexylurea. After filtration, the organic
solution was then concentrated to dryness and the residue
purified by flash chromatography (eluent: EtOH/toluene
8:2). Yield 42%; mp 192 8C; [a]D 16.2 (c 1); 1H NMR (2D-
COSY and TOCSY, pyridine-d5, 500 MHz): d (ppm): 0.99
(d, 42H, CH3), 1.20 (m, 6H, 3 CH2 antenna), 1.40 (m, 56H,
–CH2–CH2–CH2–COO), 1.57 (m, 4H, 2 CH2 antenna), 1.70
(s, 28H, CH3–CH2–), 2.36 (m, 4H, 2 CH2a–C]O antenna),
2.4–2.7 (m, 28H, CH2–COO), 4.0 (m, 1H, H-5A), 4.15 (t,
1H, H-6A), 4.2 (m, 1H, H-5 and H-6-gal), 4.35 (m, 1H,
11. Ravoo, B. J.; Darcy, R. Angew. Chem., Int. Ed. 2000, 39,
4324–4326.
12. Mazzaglia, A.; Ravoo, B. J.; Darcy, R.; Gambadauro, P.;
Mallamace, F. Langmuir 2002, 18, 1945–1948.
13. Dubes, A.; Parrot-Lopez, H.; Abdelwahed, W.; Degobert, G.;
Fessi, H.; Shahgaldian, P.; Coleman, A. W. Eur. J. Pharm.
Biopharm. 2003, 55, 279–282.
14. Tsujihara, K.; Kurita, H.; Kawazu, M. Bull. Chem. Soc. Jpn.
1977, 50, 1567.
15. (a) Lesieur, S.; Charon, D.; Lesieur, P.; Ringard-Lefebvre, C.;
ˆ
Muguet, V.; Duchene, D.; Wouessidjewe, D. Chem. Phys.
Lipids 2000, 106, 127–144. (b) Dubes, A.; Bouchu, D.;
Lamartine, R.; Parrot-Lopez, H. Tetrahedron Lett. 2001, 42,
9147–9151.
´
16. Kassab, R.; Felix, C.; Parrot-Lopez, H.; Bonaly, R.
Tetrahedron Lett. 1997, 38, 7555–7558.
A
H-4A0 ), 4.55 (dd, 1H, H-60 ), 4.3–4.5 (m, H-2, H-4, H-6,
17. Petter, R. C.; Salek, J. C.; Sikorski, C. T.; Kumaravel, G.; Lin,
F. T. J. Am. Chem. Soc. 1990, 112, 3860–3868.
H-6 , H-5), 4.6–4.72 (m, H-gal), 5.22 (d, 1H, JZ3.72 Hz,
H-1A), 5.0–5.3 (an series d, 6H, JZ3.72 Hz, H-1), 5.82 (t,
1H, H-3A), 5.90 (t, 1H, JZ7.83 Hz, H-1-gal), 5.96–6.3 (m,
6H, H-3), 8.44 (t, 1H, JZ5.8 Hz, NHb-CD), 9.55 (d, 1H,
18. Dubes, A.; Parrot-Lopez, H.; Shahgaldian, P.; Coleman, A. W.
J. Colloid Interface Sci. 2003, 259, 103–111.