Adamantoylated monosaccharides: New compounds for modification of the properties of cyclodextrin-containing materials

Article abstract of DOI:10.1016/j.carres.2005.03.017

Adamantoyl glycosides were obtained in good yields by coupling adamantanecarboxylic acid with monosaccharides. They form very stable inclusion complexes with β-cyclodextrin, as shown by ¹H NMR measurements.

Full text of DOI:10.1016/j.carres.2005.03.017

Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 1461–1468
Adamantoylated monosaccharides: new compounds for
modification of the properties of cyclodextrin-containing materials
*
C e´ cile Binkowski, Vincent Lequart, Fr e´ d e´ ric Hapiot, S e´ bastien Tilloy, Rom e´ o Cecchelli,
Eric Monflier and Patrick Martin
Laboratoire de la Barri e` re H e´ mato Enc e´ phalique, Universit e´ d’Artois, Facult e´ Jean Perrin, rue Jean Souvraz SP 18,
F-62307 Lens, France
Received 8 June 2004; accepted 10 March 2005
Abstract—Adamantoyl glycosides were obtained in good yields by coupling adamantanecarboxylic acid with monosaccharides.
1
They form very stable inclusion complexes with b-cyclodextrin, as shown by H NMR measurements.
ꢀ
2005 Elsevier Ltd. All rights reserved.
Keywords: Adamantoyl glycosides; b-Cyclodextrin; Inclusion complex
8
1. Introduction
covered by polymers of b-cyclodextrin. The cyclodex-
trin–adamantane interaction also constitutes the main
concept around which the elaboration of stabilized
nanoparticles has been developed. For example, multi-
ple host–guest interactions between an adamantyl poly-
mer and a bilayer vesicle made of amphiphilic
cyclodextrins substituted with S-dodecyl groups have
been described, leading to potential drug-delivery sys-
Modification of the properties of cyclodextrin-contain-
ing materials by the non-covalent anchoring of organic
molecules has been the subject of many investigations
during the past five years. Among the various possible
organic groups able to interact with cyclodextrins, ada-
mantyl derivatives constitute very good candidates,
since the adamantyl shape fits precisely into the b-cyclo-
dextrin cavity, leading to a high association constant
9
tems. The adamantyl moiety has also been attached
to a PEG polymer functionalized by a glycosylated
3
5
ꢀ1 1,2
10–12
13
or a transferrin ligand. In
(
K ) on the order of 10 –10 M
.
Thus, new associating polymer systems, characterized
(galactose or glucose)
A
the two last cases, the resulting vehicles were capable
of nonviral and tumor-targeted gene delivery. As a gen-
eral rule, saccharides and oligosaccharides are well
known as efficient ligands toward cellular receptors such
as lectins, promoting molecular transport through bio-
logical barriers. Recently, it has even been shown that
monosaccharides included in amphiphilic cyclodextrins
by viscosity enhancement and pH-dependent aggrega-
tion, have been elaborated starting from an adamantane
end-capped poly(ethylene oxide) or poly(b-malic acid-
co-b-ethyladamantyl malate) and a b-cyclodextrin poly-
3
–5
mer.
The same behavior has been observed upon
addition of polyethylene glycol (PEG) end-capped with
adamantyl moieties to cyclodextrin–chitosan solu-
1
4
are transferred through a bulk liquid membrane.
6
,7
tions. Optical biosensors have also been elaborated
with similar systems, in which antibodies were bound
to adamantyl dextrans immobilized onto gold surfaces
In order to elaborate glycosylated cyclodextrin materi-
als for biological applications, we have been interested in
the interaction of adamantoyl glycosides and b-cyclodex-
trin. In particular, we would like to know more about the
association constant between an adamantoyl group
chemically grafted onto a saccharide and a native b-cyclo-
dextrin. Four potential ligands for receptor-mediated
*
Corresponding author. Tel.: +33 (0)32179173; fax: +33
0)321791736; e-mail: vincentlequart@yahoo.fr
(
0
008-6215/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2005.03.017

1462
C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
targeting have retained our attention: D-glucose, D-galac-
tose, L-fucose, and L-rhamnose. Each of them has been
grafted onto an adamantoyl group and the resultant com-
pounds were included in the b-cyclodextrin cavity to form
new supramolecular compounds. We describe here the
synthesis of the adamantoyl glycosides and the determi-
compound 3 (83% yield, a/b 1:1). The mixture was
chromatographed on silica gel (9:1 hexane–EtOAc) to
separate the a- and b-anomers. Zempl e´ n deprotection of
the acetylated groups afforded the expected adamantoyl
glucosides 4a and 4b.
According to the same procedure, three other glycosyl
derivatives (AdamGal 6, AdamFuc 8, and AdamRham
10) were prepared starting from the corresponding per-
acetylated monosaccharides D-galactose, L-fucose, and
L-rhamnose. The separation of the a- and b-acetylated
glycosides were possible after chromatographic separa-
tion on silica gel (9:1 hexane–EtOAc) except for the
galactoside derivative 5. The structures of these com-
pounds are given in Scheme 2.
1
nation by H NMR measurements of their association
constants with the b-cyclodextrin.
2
. Results and discussion
The adamantyl group was introduced onto glycosyl
derivatives by ester bond formation. The general proce-
dure is described in Scheme 1.
In order to compare the position effect on monosaccha-
rides of the adamantoyl group, we also introduced this
adamantoyl group at the 3-position of D-glucopyranose
and the 6-position of D-galactopyranose. Compound 13
was readily prepared in two steps starting from 1,2:5,6-
The sugar-functionalized adamantane 4 was prepared
in three steps starting from D-glucopyranose penta-
acetate (1). The C-1 acetyl group was selectively removed
1
5
with benzylamine to give 2,3,4,6-tetra-O-acetyl-D-gluco-
pyranose (2) in 89% yield. Treatment of 2 with 1-ada-
1
7
di-O-isopropylidene-a-D-glucofuranose (11, Scheme 3).
Reaction of the diacetal 11 with 1-adamantanecarboxylic
acid in the presence of DCC and DMAP afforded
0
mantanecarboxylic acid, N,N -dicyclohexylcarbodiimide
(DCC) and 4-dimethylaminopyridine (DMAP) provided
16
OAc
O
OAc
O
OAc
O
OH
O
O
C
O
C
a
b
c
OAc
OH
O
O
OAc
OAc
OAc
OH
AcO
AcO
AcO
HO
OAc
OAc
OAc
OH
1
2
3
4
Scheme 1. General procedure for synthesis of adamantoylated monosaccharides. Reagents and conditions: (a) BnNH
2
, THF, rt; (b) AdamCO
2
H,
DCC, DMAP, CH Cl
2
2
, rt; (c) NaOMe, MeOH, rt.
OR1
O
1
1
R O
O
O
R O
CH3
1
CH3
OR1
OCOAdam
OCOAdam
OCOAdam
R O
1
R O
OR1
OR1
1
OR1
1
R O
1
1
Adam
5
6
: R =Ac
7: R =Ac
9: R =Ac
1
1
1
: R =H
8: R =H
10: R =H
Scheme 2. Structures of adamantoyl glycoside derivatives based on the monosaccharides D-galactose (5 and 6), L-fucose (7 and 8), and L-rhamnose
9 and 10).
(
OR1
O
O
O
OH
O
OCOAdam
O
O
OR1
HO
Adam-CO
HO
O
OH
O
OH
OH
O
O
O
O
OH
O
1
OH
1
1
1
1: R = H
2: R = COAdam
13
14 : R = H
16
1
1
15 : R = COAdam
Scheme 3. Structures of adamantoyl glycoside derivatives with the adamantoyl part attached at the 3-position (13) and 6-position (16).

C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
1463
OR1
O
rived from the titration curves were found to lie between
4
ꢀ1
6
ꢀ1
O
3.6 · 10 M and 1.9 · 10 M (Table 1).
CH3
1
OR1
These values clearly indicate that all modified mono-
saccharides are very strongly bound to the cyclodextrin,
proving that the adamantoyl moiety is a valuable group
for increasing the affinity of monosaccharides toward
cyclodextrin. Interestingly, it seems that the carbohy-
drate moiety also plays an important role in stabilizing
the inclusion complex, as the association constants de-
pend on the position of the adamantoyl group on the
monosaccharide. In particular, the molecular recogni-
tion was the highest when the adamantoyl group was
introduced at the anomeric position (see 4 and 6). There-
fore, in addition of the strong interaction between the
adamantoyl moiety and the cavity of the cyclodextrin,
hydrogen bonds between the cyclodextrin and the four
hydroxyl groups of the adamantoyl glucoside 4 or the
adamantoyl galactoside 6 derivatives are also thought
to be responsible for the strength of the host–guest inter-
action. This hypothesis was confirmed by the results ob-
tained with the more lipophilic saccharides 8 and 10,
which present lower association constants than those
of the hydrophilic derivatives 4 and 6. Compounds 8
and 10 have only three hydroxyl groups, whose ability
of forming hydrogen bonds with the hydroxyl groups
of the cyclodextrin is thus lower. Finally, we note that
the anomeric configuration has a small effect on the
association-constant values. Comparing adamantoyl
glucosides 4a and 4b, the association constant is signifi-
cantly higher when the adamantoyl group is attached in
the b-orientation.
R O
1
2
1
R2
R O
R
OR
R O
1
OR1
1
1
2
1
1
1
2
7: R = Ac, R2 = Br
21: R = Ac, R = Br
1
2
1
2
12
8: R = Ac, R = O-C H -OH
22: R = Ac, R = O-C H -OH
4
8
4 8
9: R = Ac, R2 = O-C H -OCO-Adam
1
23: R = Ac, R = O-C H -OCO-Adam
4 8
1
2
4
8
0: R = H, R2 = O-C H -OCO-Adam 24: R = H, R2 = O-C H -OCO-Adam
1
1
4
8
4 8
Scheme 4. Adamantoylated glycosyl derivatives containing an alkyl
spacer between the adamantoyl part and the monosaccharide moiety.
compound 12 after column chromatography on silica gel.
Removal of the isopropylidene groups with 9:1
CF CO OH–H O afforded the expected adamantoyl
derivative 13 in 71% yield.
By the same method, we also prepared the galactosyl
derivative 16, starting from 1,2:3,4-di-O-isopropylidene-
a-D-galactopyranose 14 (Scheme 3). The adamantoyl
group was first attached at the 6-position (69% yield)
and the isopropylidene groups were then removed, giv-
ing compound 16 in 71% yield.
In order to compare the influence of the sugar part on
the association constant, an alkyl chain was intercalated
between the sugar and adamantoyl moieties. We thus
synthesized two other derivatives, starting from peracet-
ylated glucose or fucose (Scheme 4).
Reaction of butan-1,4-diol with tetra-O-acetyl-a-D-
glucopyranosyl bromide (17) or 2,3,4-tri-O-acetyl-a-L-
fucopyranose bromide (21) in the presence of AgOTf
by the method of Hanessian and Banoub provided
the desired products 18 and 22. The adamantoyl group
was then introduced by the method already described,
using 1-adamantanecarboxylic acid, DCC and DMAP.
Zempl e´ n deprotection of the acetylated groups afforded
the expected adamantoyl glycosides 20 and 24.
3
2
2
1
8
With the alkyl spacer-containing compounds 20b and
1
9
4
24a, the association constants are 1.8 · 10 and
4
ꢀ1
4.8 · 10 M respectively. It is noteworthy that, when
comparing the two glucosylated derivatives 4b and
20b, a very strong decrease in the association constant
is observed when a spacer is introduced between the glu-
6
4
ꢀ1
cose and adamantoyl parts (1.9 · 10 vs 1.8 · 10 M
,
The ability of adamantoyl glycosides to form inclu-
sion complexes with the native b-cyclodextrin was inves-
tigated by H NMR spectroscopy. The stoichiometry of
respectively). Once more, this clearly shows that the glu-
cose moiety takes part in the association with cyclodex-
trin. More precisely, when the affinity of the sugar for
the cyclodextrin is strong, the addition of a spacer
moves the saccharide away from the hydroxyl groups
of the cyclodextrin and the association constant de-
creases. On the other hand, for fucosylated derivatives
1
the inclusion complexes was determined by the continu-
2
0,21
ous variation technique (JobÕs method) and the
association constants KA at 298 K of these complexes
was determinated by computer fitting of the chemical-
22
shift titration curves of the adamantoyl protons. For
all monosaccharides, the JobÕs plots were highly sym-
metrical and showed a maximum at r = 0.5, undoubt-
edly indicating the formation of a 1:1 inclusion
8a and 24a, the spacer has only a moderate influence
4
on
the
4
association
constant
(3.9 · 10
vs
ꢀ1
4.8 · 10 M ). Therefore, when the interaction between
the saccharide and the cyclodextrin is quite low, the
addition of an alkyl spacer between the sugar moiety
2
0
complex. The values of these association constants de-
Table 1. Association constants K
A
at 298 K
4b
1.9 · 10
Compound
4a
6
8a
8b
10a
10b
13
16
ꢀ1
6
6
5
4
4
4
4
5
5
K
A
(M
)
1.5 · 10
8.1 · 10
3.9 · 10
3.6 · 10
5.1 · 10
4.6 · 10
2.2 · 10
4.3 · 10

1464
C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
and the adamantoyl group does not significantly modify
the stability of the inclusion complex. In that case, the
value of the association constant is rather the result of
the adamantoyl–cyclodextrin interaction.
dOBS ¼ ðdAdam.½Adam.ꢁ
þ dCOMP½COMPꢁÞ=½Adam.ꢁT
ð1Þ
ð2Þ
In conclusion, grafting of the adamantoyl group onto
monosaccharides has led to new compounds that interact
strongly with b-cyclodextrin. The interaction between
those two compounds is due not only to the strong inter-
action between the adamantoyl group and the lipophilic
cavity of the cyclodextrin, but depends also on the num-
ber of hydrogen bonds between the hydroxyl groups of
the saccharide and those of the cyclodextrin. The ability
of these compounds to bind to more sophisticated cyclo-
dextrin-containing materials and to generate particular
biological properties is now under investigation.
2
½
COMPꢁ ¼ ꢀ1=2½ð1=K
A
þ ½b-CDꢁ þ ½Adam.ꢁ Þ
1=2
T
T
ꢀ 4½b-CDꢁ ½Adam.ꢁ ꢁ þ 1=2ð1=KA
T
T
þ ½b-CDꢁ þ ½Adam.ꢁ Þ
T
T
where K , T, and d
denote the formation constant,
A
Adam.
the total, and the chemical shift of protons of the ada-
mantoyl group in the absence of b-CD, respectively.
For a given value of K , [COMP] is known and d
A
COMP
may be calculated from (1) for each [CD] . The standard
T
deviation over dCOMP had then to be minimized relative
to K. The adamantoyl concentration was fixed at 1 mM
and b-CD varied from 0 to 3 mM.
3. Experimental
3.2. 2,3,4,6-Tetra-O-acetyl-1-O-adamantoyl-D-glucopyr-
anose (3)
3
.1. General methods
Melting points were determined on an electrothermal
automatic apparatus, and are uncorrected. NMR spec-
tra were recorded with a Bruker WB-300 instrument
for solutions in CDCl (internal Me Si). All compounds
To a solution of 2,3,4,6-tetra-O-acetyl-D-glucopyranose
(2) (1.0 g, 2.9 mmol) in CH Cl (10 mL) was successively
2
2
added DCC (2.3 g, 11.5 mmol), DMAP (0.7 g,
2.9 mmol), and 1-adamantanecarboxylic acid (1.0 g,
5.8 mmol). After 3 h at 50 ꢁC, the mixture was diluted
with CH Cl (10 mL), filtered, and the filtrate evapo-
3
4
1
13
were characterized by acquisition of H, C, DEPT,
1
1
H– H COSY, and H– C correlated experiments.
1
13
2
2
Reactions were monitored by high-performance liquid
chromatography (HPLC, Variant) using a reverse-phase
column RP-18 (E. Merck). Analytical thin-layer chro-
matography (TLC) was performed on E. Merck alumi-
num-backed silica gel (Silica Gel F254). IR spectra
were recorded with a Bruker Vector 22 instrument. Col-
umn chromatography was performed on silica gel (60
mesh, Matrex) by gradient elution with hexane–acetone
or hexane–EtOAc (in each case the ratio of silica gel to
product mixture to be purified was 30:1).
rated. Chromatography of the residue on a column of
silica gel (9:1 hexane–EtOAc) gave 3 in 83% yield, a/b
ꢀ
1
1
1:1; anomer 3a; oil; IR; m 1741.5 cm (CO); H NMR
(CDCl , 300 MHz): d 6.34 (d, 1H, J 3.6 Hz, H-1),
3
1,2
5.46 (t, 1H, J3,4 9.3 Hz, H-3), 5.17 (t, 1H, H-4), 5.09
(dd, 1H, J2,3 10.2 Hz, H-2), 4.28 (m, 1H, J6a,6b
11.9 Hz, J5,6a 4.6 Hz, H-6a), 4.10 (m, 2H, J5,6b 2.3 Hz,
H-5, H-6b), 2.10–1.96 (4s, 12H, CH CO), 2.16–1.70
3
1
3
(m, 15H, Adam); C NMR (CDCl , 75.5 MHz): d
3
175.6 (COAdam), 171.0–169.8 (CH CO), 89.0 (C-1),
3
7
0.4 (C-3), 70.3 (C-5), 69.9 (C-2), 69.3 (C-4), 61.9 (C-
6), 41.6, 38.8, 36.7, 28.1 (Adam), 21.1–20.8 (CH CO);
3
.1.1. Determination of stoichiometry. The continuous
3
variation method was adopted to determine the stoichio-
metry of the b-CD–adamantoyl complex. A series of
samples containing varied ratios (from 0 to 1) of b-CD
and the adamantoyl derivative was prepared, keeping
the total concentration of species constant (1 mM in this
anomer 3b; white crystals; mp 175–178 ꢁC; IR; m
ꢀ
1
1
1740.9 cm
(CO); H NMR (CDCl , 300 MHz): d
3
5.68 (d, 1H, J1,2 7.8 Hz, H-1), 5.23 (m, 2H, H-2, H-3),
5.16 (dd, 1H, J3,4 9.2 Hz, J4,5 9.8 Hz, H-4), 4.29 (dd,
1H, J6a,6b 12.4 Hz, J5,6a 4.0 Hz, H-6a), 4.08 (dd, 1H,
J5,6b 1.9 Hz, H-6b), 3.83 (m, 1H, H-5), 2.10–2.02 (4s,
1
present case). The differences of chemical shift in the H
NMR spectra for the adamantoyl proton were measured
1
3
12H, CH CO), 2.16–1.70 (m, 15H, Adam); C NMR
3
as a function of the molar ratio (r). The DDH(Adam)*
(CDCl , 75.5 MHz): d 175.9 (COAdam), 171.0–169.5
3
[
Adam] was traced as a function of the molar ratio (r).
.1.2. Determination of the association constant. One
proton of the adamantoyl group (Adam) was chosen
(CH CO), 91.9 (C-1), 73.0 (C-3, C-5), 70.5 (C-2), 68.4
3
(C-4), 61.9 (C-6), 41.1, 38.8, 36.7, 28.0 (Adam), 21.1–
20.9 (CH CO). Anal. Calcd for C H O : C, 58.81;
H, 6.71. Found: C, 58.75; H, 6.69.
3
3
25 34 11
1
for evaluating the association constant by H NMR
spectroscopy. Assuming a 1:1 inclusion mechanism,
the observed chemical shift of the protons the adamant-
oyl group (dOBS) and the complex concentration
3.3. 1-O-Adamantoyl-a-D-glucopyranose (4a)
To a stirred solution of 3a (500 mg, 0.98 mmol) in
MeOH (0.5 mL) was added NaOMe (4 mg, 0.01 mmol).
[
COMP] are described as follows:

C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
1465
After 1 h at rt, the mixture was evaporated. Chromato-
graphy of the residue on a column of silica gel (1:1 hex-
3.7. 2,3,4-Tri-O-acetyl-1-O-adamantoyl-L-fucopyranose
(7)
ane–EtOAc) gave 4a in 55% yield as a oil; IR; m 3348.1
ꢀ
1
13
(COAdam); C NMR (CDCl3,
(
OH), 1726.1 cm
A procedure similar to that for the preparation of 3 was
employed. Treatment of 2,3,4-tri-O-acetyl-L-fucopyran-
ose (1 g, 3.4 mmol), 1-adamantanecarboxylic acid
(1.24 g, 13.6 mmol) with DCC (7.11 g, 13.6 mmol),
7
7
3
5
5.5 MHz): d 178.4 (COAdam), 91.6 (C-1), 72.4 (C-3),
0.3 (C-5), 68.0, 67.1 (C-2, C-4), 61.8, (C-6), 40.8,
9.2, 36.9, 28.5 (Adam). Anal. Calcd for C H O : C,
1
7
26
7
9.63; H, 7.66. Found: C, 59.51; H, 7.56.
DMAP (1.42 g, 3.4 mmol) at 50 ꢁC gave 7 in 66% yield,
1
a/b 1:1; anomer 7a, oil, H NMR (CDCl , 300 MHz): d
3
3
.4. 1-O-Adamantoyl-b-D-glucopyranose (4b)
6.36 (d, 1H, J1,2 3.2 Hz, H-1), 5.35 (m, 2H, H-3, H-4),
5.31 (m, 1H, H-2), 3.92 (m, 1H, J5,6 6.0 Hz, H-5),
2.17–1.93 (3s, 9H, CH CO), 2.16–1.69 (m, 15H, Adam),
A procedure similar to that for the preparation of 4a
was employed. Treatment of 3b (500 mg, 0.98 mmol)
in MeOH (0.5 mL) with NaOMe (4.0 mg, 0.01 mmol)
gave 4b in 58% yield as a white crystalline material;
3
3
1
1.19 (d, 3H, H-6); C NMR (CDCl , 75.5 MHz): d
3
176.0 (COAdam), 171.0–170.2 (CH CO), 89.8 (C-1),
71.0 (C-3), 68.5 (C-4), 67.6 (C-5), 67.1 (C-2), 41.1,
38.8, 36.7, 28.8 (Adam), 21.2–21.0 (CH CO), 16.4 (C-
3
1
3
mp 94–96 ꢁC; C NMR (CDCl , 75.5 MHz): d 178.4
3
3
1
(
COAdam), 94.7 (C-1), 72.1 (C-3), 71.2, (C-5), 67.9,
7.2 (C-2, C-4), 61.3 (C-6), 40.8, 39.2, 36.9, 28.5 (Adam).
Anal. Calcd for C H O : C, 59.63; H, 7.66. Found: C,
6); anomer 7b, white crystals, mp 138–140 ꢁC;
H
6
NMR (CDCl , 300 MHz): d 5.65 (d, 1H, J 8.2 Hz,
3 1,2
H-1), 5.34 (dd, 1H, J2,3 10.0 Hz, H-2), 5.27 (d, 1H, H-
4), 5.07 (dd, 1H, J3,4 3.3 Hz, H-3), 3.95 (m, 1H, J5,6
1
7
26
7
5
9.60; H, 7.63.
6.0 Hz, H-5), 2.16–1.70 (m, 15H, Adam), 2.15–1.90
(3s, 9H, CH CO), 1.23 (d, 3H, H-6); C NMR (CDCl3,
1
3
3.5. 2,3,4,6-Tetra-O-acetyl-1-O-adamantoyl-D-galacto-
pyranose (5)
3
75.5 MHz): d 176.2 (COAdam), 171.0–169.8 (CH CO),
3
92.5 (C-1), 71.6 (C-3), 70.7 (C-5), 70.5 (C-4), 68.3 (C-
2), 41.1, 38.9, 36.3, 28.2 (Adam), 21.1–20.9 (CH CO),
A procedure similar to that for the preparation of 3 was
employed. Treatment of 2,3,4,6-tetra-O-acetyl-D-galac-
topyranose (1.0 g, 2.9 mmol), 1-adamantanecarboxylic
acid (1.0 g, 5.8 mmol) with DCC (2.3 g, 11.5 mmol),
DMAP (0.7 g, 2.9 mmol) at 50 ꢁC gave 5 in 89% yield
3
16.3 (C-6). Anal. Calcd for C H O : C, 60.72; H,
34 10
2
5
6.93. Found: C, 60.65; H, 6.89.
3.8. 1-O-Adamantoyl-a-L-fucopyranose (8a)
1
as white crystals, a/b 1:4; mp 133–135 ꢁC; H NMR
(
CDCl , 300 MHz): d 6.32 (d, 1H, J1,2 2.9 Hz, H-1a),
A procedure similar to that for the preparation of 4a
was employed. Treatment of 7a (500 mg, 1.1 mmol) in
MeOH (0.5 mL) with NaOMe (5 mg, 0.11 mmol) gave
3
5
0
.60 (d, 1H, J1,2 8.3 Hz, H-1b), 5.45 (dd, 1H, J4,5
.7 Hz, H-4a), 5.36 (dd, 1H, J4,5 1.0 Hz, H-4b), 5.29
1
3
(
dd, 1H, J2,3 10.4 Hz, H-2b), 5.25 (dd, 1H, J2,3 9.8 Hz,
8a in 51% yield as white crystals; mp 77–79 ꢁC;
C
H-2a), 5.01 (dd, 1H, J3,4 3.4 Hz, H-3b), 4.97 (dd, 1H,
H-3a), 4.01–4.06 (m, 2H, H-6b), 3.97 (m, 1H, H-5a,
NMR (CDCl , 75.5 MHz): d 176.8 (COAdam), 94.6
3
(C-1), 74.9 (C-2), 72.0, 71.7 (C-3, C-4), 70.8 (C-5), 16.7
(C-6), 41.4–28.2 (Adam). Anal. Calcd for C H O :
C, 62.56; H, 8.03. Found: C, 62.41; H, 7.85.
H-5b), 2.10–1.93 (4s, 12H, CH CO), 2.11–1.68 (m,
3
17 26
6
1
3
1
1
8
3
4
5H, Adam); C NMR (CDCl , 75.5 MHz): d 176.0,
3
75.6 (COAdam), 171.0–169.8 (CH CO), 92.4 (C-1b),
3
9.6 (C-1a), 72.0 (C-5b, C-5a), 71.2 (C-3b), 69.1 (C-
a), 68.1 (C-2b), 68.0, 67.8, 67.1 (C-2a, C-4a), 67.2 (C-
b), 61.6 (C-6a), 61.3 (C-6b), 41.1, 39.7, 36.7, 28.1
3.9. 1-O-Adamantoyl-b-L-fucopyranose (8b)
A procedure similar to that for the preparation of 4a
was employed. Treatment of 7b (500 mg, 1.1 mmol) in
MeOH (0.5 mL) with NaOMe (5 mg, 0.11 mmol) gave
(
C H O : C, 58.81; H, 6.71. Found: C, 58.72; H, 6.67.
Adam), 21.0–20.9 (CH CO). Anal. Calcd for
3
2
5
34 11
1
3
8
b in 50% yield as an oil;
75.5 MHz): d 176.8 (COAdam), 92.4 (C-1), 74.9 (C-2),
1.8, 71.4 (C-3, C-4), 70.8 (C-5), 16.6 (C-6), 41.4–28.2
(Adam). Anal. Calcd for C H O : C, 62.56; H, 8.03.
C NMR (CDCl3,
3
.6. 1-O-Adamantoyl-D-galactopyranose (6)
7
A procedure similar to that for the preparation of 4 was
employed. Treatment of 5 (500 mg, 0.98 mmol) in
MeOH (0.5 mL) with NaOMe (4.0 mg, 0.01 mmol) gave
1
7
26
6
Found: C, 62.46; H, 7.94.
1
3
6
in 64% yield as white crystals, a/b 1:2; C NMR
3.10. 2,3,4-Tri-O-acetyl-1-O-adamantoyl-L-rhamno-
pyranose (9)
(
CDCl , 75.5 MHz): d 176.2 (COAdam), 94.7 (C-1b),
3
9
1.3 (C-1a), 72.6, 72.1 (C-3), 71.0, 70.7 68.1, 67.5, 67.1
C-2, C-4, C-5), 62.4, 61.3 (C-6), 41.0–28.4 (Adam).
Anal. Calcd for C H O : C, 59.63; H, 7.66. Found:
(
A procedure similar to that for the preparation of 3 was
employed. Treatment of 2,3,4-tri-O-acetyl-L-rhamno-
pyranose (1 g, 3.4 mmol), 1-adamantanecarboxylic acid
1
7
26
7
C, 59.55; H, 7.58.

1466
C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
1
3
(
1.24 g, 13.6 mmol) with DCC (7.11 g, 13.6 mmol),
Adam), 1.59–1.44 (4s, 12H, CH3); C NMR (CDCl3,
75.5 MHz): d 176.4 (COAdam), 112.1, 109.3 (Ciso),
105.7 (C-1), 82.9 (C-3), 82.5 (C-2), 81.6 (C-4), 72.9
(C-5), 67.6 (C-6), 41.1–38.9 (Adam), 27.2–24.5 (CH3).
Anal. Calcd for C H O : C, 65.38; H, 8.11. Found:
DMAP (1.42 g, 3.4 mmol) at 50 ꢁC gave 9 in 85% yield,
a/b 1/3; anomer 9a, oil, H NMR (CDCl , 300 MHz): d
6
(
1
3
.00 (d, 1H, J1,2 1.2 Hz, H-1), 5.28 (m, 1H, H-3), 5.25
m, 1H, H-4), 5.11 (m, 1H, J2,3 3.4 Hz, H-2), 3.91 (m,
23
34
7
1
2
H, J5,6 6.3 Hz, H-5), 2.22–2.00 (3s, 9H, CH CO),
3
C, 65.26; H, 8.04.
1
3
.00–1.61 (m, 15H, Adam), 1.24 (d, 3H, H-6);
C
NMR (CDCl , 75.5 MHz): d 175.4 (COAdam), 170.6–
3.14. 3-O-Adamantoyl-D-glucose (13)
3
1
70.2 (CH CO), 90.8 (C-1), 70.7 (C-4), 69.4, 69.0 (C-3,
3
C-2), 69.2 (C-5), 41.1, 38.8, 36.7, 28.8 (Adam), 21.2–
1.0 (CH CO), 17.8 (C-6); anomer 9b, white crystals,
A suspension of diacetal derivative 12 (500 mg, 1.8 mmol)
in a solution of 9:1 CF CO OH–water (0.5 mL) was stir-
2
3
3
2
1
mp 133–135 ꢁC; H NMR (CDCl , 300 MHz): d 5.81
red at rt. After 30 min, the solvent was removed by co-
evaporation with toluene (5 mL). Chromatography of
the residue on a column of silica gel (2:3 hexane–EtOAc)
gave 13 in 71% yield as white crystals, a/b 3:7; mp 142–
3
(
d, 1H, J 1.0 Hz, H-1), 5.48 (dd, 1H, J 3.4 Hz, H-
1,2 2,3
2
J5,6 6.2 Hz, H-5), 1.29 (d, 3H, H-6); C NMR (CDCl3,
), 5.09 (m, 2H, H-3, H-4), 3.67 (m, 1H, J 9.6 Hz,
4,5
1
3
ꢀ
1
13
7
5.5 MHz): d 90.7 (C-1), 71.8 (C-5), 71.0, 70.9 (C-3, C-
144 ꢁC; IR; m 3370.2 (OH), 1718.9 cm (COAdam);
C
4), 68.9 (C-2), 17.7 (C-6). Anal. Calcd for C H O :
C, 60.72; H, 6.93. Found: C, 60.68; H, 6.91.
NMR (CDCl , 75.5 MHz): d 176.7 (COAdam), 97.6 (C-
2
5
34 10
3
1b), 93.0 (C-1a), 78.1, 77.4 (C-3); 77.4, 75.8, 72.8, 71.3,
6
9.0, (C-2, C-4, C-5), 61.6 (C-6), 41.1, 39.4–37.0 (Adam).
Anal. Calcd for C H O : C, 59.64; H, 7.65. Found: C,
3
.11. 1-O-Adamantoyl-a-L-rhamnopyranose (10a)
1
7
26
7
5
9.58; H, 7.57.
A procedure similar to that for the preparation of 4a
was employed. Treatment of 9a (500 mg, 1.1 mmol) in
MeOH (0.5 mL) with NaOMe (5 mg, 0.11 mmol) gave
3.15. 6-O-Adamantoyl-1,2:5,6-di-O-isopropylidene-
a-D-galactofuranose (15)
1
0a in 45% yield as white crystals; mp 125–126 ꢁC; IR;
ꢀ
1 13
(COAdam); C NMR
m 3291.5 (OH), 1726.1 cm
A procedure similar to that for the preparation of 3 was
employed. Treatment of 1,2:5,6-di-O-isopropylidene-a-
D-galactofuranose 14 (1 g, 3.8 mmol), 1-adamantane-
(
CDCl , 75.5 MHz): d 176.1 (COAdam), 93.5 (C-1),
3
1
8
7
(
3.0 (C-2), 72.0 (C-3), 71.3, 71.0 (C-4, C-5), 41.5-36.7
Adam), 18.0 (C ). Anal. Calcd for C H O : C,
carboxylic acid (1.38 g, 7.7 mmol) with DCC (3.17 g,
15.4 mmol), DMAP (0.47 g, 3.8 mmol) at 50 ꢁC gave
6
17 26
6
6
2.56; H, 8.03. Found: C, 62.49; H, 7.92.
1
1
5 as white crystals in 76% yield; mp 122–123 ꢁC; H
3
.12. 1-O-Adamantoyl-b-L-rhamnopyranose (10b)
NMR (CDCl , 300 MHz): d 5.55 (d, 1H, J 5.0 Hz,
3 1,2
H-1), 4.62 (dd, 1H, J3,4 7.9 Hz, H-3), 4.38 (dd, 1H, J2,3
2.4 Hz, H-2), 4.33 (d, 1H, J4,5 1.8 Hz, H-4), 4.13 (m,
1H, J5,6 6.2 Hz, H-5), 4.05 (m, 2H, H-6), 2.10–1.72 (m,
A procedure similar to that for the preparation of 4a
was employed. Treatment of 9b (500 mg, 1.1 mmol) in
MeOH (0.5 mL) with NaOMe (5 mg, 0.11 mmol) gave
1
3
15H, Adam), 1.59–1.44 (4s, 12H, CH3); C NMR
(CDCl , 75.5 MHz): d 176.3 (COAdam), 110.0, 109.2
1
0b in 50% yield as white crystals; mp 133–134 ꢁC;
3
1
3
C NMR (CDCl , 75.5 MHz): d 176.1 (COAdam),
(C ), 96.7 (C-1), 71.5 (C-4), 71.1 (C-2), 70.9 (C-3),
iso
3
9
C-5), 41.5-36.7 (Adam), 18.0 (C ). Anal. Calcd for
3.5 (C-1), 73.0 (C-2), 72.0 (C-3), 71.3, 71.0 (C-4,
66.6 (C-5), 63.5 (C-6), 41.1–36.9 (Adam), 26.4, 24.9
(CH ). Anal. Calcd for C H O : C, 65.38; H, 8.11.
Found: C, 65.26; H, 8.07.
6
3
23 34
7
C H O : C, 62.56; H, 8.03. Found: C, 62.44; H,
6
1
7
26
7
.89.
3
.16. 6-O-Adamantoyl-D-galactose (16)
3
.13. 3-O-Adamantoyl-1,2:5,6-di-O-isopropylidene-
a-D-glucofuranose (12)
A suspension of diacetal derivative 15 (500 mg, mmol) in
a solution of 9:1 CF CO OH–water (0.5 mL) was stirred
3
2
A procedure similar to that for the preparation of 3
was employed. Treatment of 1,2:5,6-di-O-isopropylid-
ene-a-D-glucofuranose 11 (1 g, 3.8 mmol), 1-adaman-
tanecarboxylic acid (1.38 g, 7.7 mmol) with DCC
at rt. After 30 min, the solvent was removed by co-evapo-
ration with toluene (5 mL). Chromatography of the res-
idue on a column of silica gel (2:3 hexane–EtOAc) gave
16 in 71% yield as white crystals, a/b 3:1; mp 101–
1
7
ꢀ
1
(
3.17 g, 15.4 mmol), DMAP (0.47 g, 3.8 mmol) at
102 ꢁC; IR; m 3379.2 (OH), 1703.9 cm
(COAdam);
1
3
5
1
0 ꢁC gave 12 in 69% yield as white crystals; mp 110–
C NMR (CDCl , 75.5 MHz): d 176.3 (COAdam),
3
1
12 ꢁC; H NMR (CDCl , 300 MHz): d 5.87 (d, 1H,
98.1 (C-1b), 93.4 (C-1a); 74.0, 72.7 (C-3); 73.2, 70.4,
69.8, 69.2 (C-2, C-4, C-5); 65.6 (C-6); 40.8–36.7 (Adam).
Anal. Calcd for C H O : C, 59.64; H, 7.65. Found: C,
3
J1,2 3.7 Hz, H-1), 4.51 (d, 1H, H-2), 4.31 (q, 1H, H-
5
), 4.11 (dd, 1H, J4,5 7.4 Hz, H-4), 4.00 (d, 1H, J3,4
.6 Hz, H-3), 4.05 (m, 2H, H-6), 2.08–1.72 (m, 15H,
17
26
7
3
59.55; H, 7.54.

C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
1467
3.17. 4-(2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyloxy)-
butanol (18)
20 in 67% yield as white crystals; mp 75–77 ꢁC; IR; m
1
3356.1 (OH), 1723.4 cm (COAdam); [M+Na] m/z
ꢀ
+•
1
4
37.4; H NMR (CDCl , 300 MHz): d 4.32 (d, 1H, J
3 1,2
To a stirred solution of tetra-O-acetyl-a-D-glucopyrano-
syl bromide (17, 1 g, 2.4 mmol) and 1,4-butandiol
8.0 Hz, H-1), 4.08 (t, 2H, CH ), 3.93, 3.57 (2m, 2H,
2d
CH ), 3.86 (m, 2H, H-6), 3.62–3.53 (m, 2H, H-3, H-
2a
˚
441 mg, 4.8 mmol) and 4 A MS (1 g) in anhyd CH Cl
(
(
4), 3.39 (m, 1H, J2,3 9.5 Hz, H-2), 3.32 (m, 1H, H-5),
3
2
2
1
10 mL), was added tetramethylurea (0.28 mL,
.4 mmol) and AgOTf (0.54 g, 2.4 mmol) at 0 ꢁC in the
dark. After stirring for 12 h, the reaction was quenched
2.04–1.69 (m, 15H, Adam), 1.71 (CH , CH );
2
C
d
2v
2
NMR (CDCl , 75.5 MHz): d 178.4 (COAdam), 103.2
3
(C-1), 76.8 (C-3) 76.0 (C-5), 73.8 (C-2), 69.9 (CH ),
69.8 (C-4), 64.2 (CH ), 61.8 (C-6), 41.1, 39.2, 36.9,
2d
2a
with Et N, filtered and then evaporated. Chromatogra-
3
phy of the residue on a column of silica gel (3:2 hex-
1
ane–EtOAc) gave 18 in 75% yield as an oil; H NMR
28.5 (Adam), 26.3, 25.7 (CH , CH ). Anal. Calcd for
2b 2v
C H O : C, 60.85; H, 8.27. Found: C, 60.75; H, 8.19.
21 34 8
(
CDCl , 300 MHz): d 5.17 (t, 1H, J3,4 9.4 Hz, H-3),
3
5.06 (t, 1H, J4,5 9.8 Hz, H-4), 4.96 (dd, 1H, J2,3
9.5 Hz, H-2), 4.48 (d, 1H, J1,2 7.9 Hz, H-1), 4.25 (dd,
1H, J6a,6b 12.3 Hz, J5,6a 4.7 Hz, H-6a), 4.11 (dd, 1H,
3.20. 4-(2,3,4-Tri-O-acetyl-b-L-fucopyranosyloxy)butanol
(22)
J5,6b 2.5 Hz, H-6b), 4.19–4.00 (m, 2H, CH ), 3.89,
2d
A procedure similar to that for the preparation of 18
was employed. Treatment of 21 (1 g, 2.8 mmol), 1,4-
butandiol (512 mg, 5.7 mmol) with tetramethylurea
(330 mg, 2.8 mmol) and AgOTf (627 mg, 2.8 mmol) at
3
1
.50 (2m, 2H, CH ), 3.67 (m, 1H, H-5), 2.12–1.97 (4s,
2a
2H, CH CO), 2.03 (m, 2H, CH ), 1.91 (m, 2H,
3
2d
1
3
CH ); C NMR (CDCl , 75.5 MHz): d 171.2–169.8
2
v
3
1
(
CH CO), 101.0 (C-1), 73.1 (C-3), 72.0 (C-5), 71.7 (C-
3
0 ꢁC in the dark gave 22 in 71% yield as an oil; H
2
), 70.3 (CH ), 68.8 (C-4), 62.4 (CH ), 62.2 (C-6),
2
NMR (CDCl , 300 MHz): 5.22 (d, 1H, H-4), 5.17 (dd,
1H, J2,3 10.4 Hz, H-2), 5.00 (dd, 1H, J3,4 3.4 Hz, H-3),
4.43 (d, 1H, J1,2 7.9 Hz, H-1), 3.94, 3.63, 3.50 (3m,
a
2d
3
2
Calcd for C H O : C, 51.43; H, 6.71. Found: C,
9.4, 26.1 (CH , CH ), 21.1–20.9 (CH CO). Anal.
2
b
2v
3
1
8
28 11
5
1.37; H, 6.64.
4H, CH , CH ), 3.79 (dq, 1H, J
2
1.0 Hz, J5,6
4.5
d
2a
6.4 Hz, H-5), 2.18–1.70 (m, 15H, Adam), 2.16–1.97
(3s, 9H, CH CO), 2.00 (CH ), 1.63 (CH ), 1.21 (d,
3
.18. 4-Adamantoyloxy-1-(2,3,4,6-tetra-O-acetyl-
3
3
2d
2v
1
a-D-glucopyranosyloxy)butane (19)
2H, H-6); C NMR (CDCl , 75.5 MHz): d 171.1–
3
170.0 (CH CO), 101.5 (C-1), 71.7 (C-3), 70.7 (C-4),
3
A procedure similar to that for the preparation of 3 was
employed. Treatment of 18 (0.5 g, 1.2 mmol), 1-ada-
mantanecarboxylic acid (2.8 g, 2.4 mmol) with DCC
70.2 (CH ), 69.5, 69.4 (C-2, C-5), 62.7 (CH ), 29.8
2a 2d
(CH ), 26.2 (CH , CH ), 21.2–21.0 (CH CO), 16.4
3
2
v
2b
2v
(C-6). Anal. Calcd for C H O : C, 53.46; H, 6.98.
1
8
28 10
(
1.3 g, 4.8 mmol), DMAP (0.14 g, 1.2 mmol) at 50 ꢁC
Found: C, 53.40; H, 6.94.
ꢀ1
gave 19 in 74% yield as an oil; IR (cm ); m 1746.7
ꢀ1
1
(Adam); H NMR (CDCl3,
(
CH CO), 1723.5 cm
3.21. 4-Adamantoyloxy-1-(2,3,4-tri-O-acetyl-b-L-fuco-
pyranosyloxy)butane (23)
3
3
00 MHz): d 5.13 (t, 1H, J3,4 9.4 Hz, H-3), 5.00 (t, 1H,
J4,5 9.6 Hz, H-4), 4.91 (dd, 1H, J2,3 9.4 Hz, H-2), 4.45
d, 1H, J1,2 7.9 Hz, H-1), 4.20 (dd, 1H, J6a,6b 12.2 Hz,
J5,6a 4.6 Hz, H-6a), 4.05 (dd, 1H, J5,6b 2.5 Hz, H-6b),
(
A procedure similar to that for the preparation of 3 was
employed. Treatment of 22 (500 mg, 1.4 mmol), 1-ada-
mantanecarboxylic acid (0.5 g, 2.8 mmol) with DCC
(1.14 g, 5.5 mmol), DMAP (0.17 g, 1.4 mmol) at 50 ꢁC
4
.04, 3.82 (m, 2H, CH ), 3.82, 3.55 (2m, 2H, CH ),
2d 2a
3
.63 (m, 1H, H-5), 2.02–1.91 (4s, 12H, CH CO), 1.97
3
(
1
m, 2H, CH ), 1.58 (m, 2H, (CH )), 2.16–1.67 (m,
2v
gave 23 in 68% yield as an oil; IR: 1746.8 (CH CO),
3
2
d
1
3
ꢀ1
1
1723.8 cm (COAdam); H NMR (CDCl , 300 MHz):
5H, Adam); C NMR (CDCl , 75.5 MHz): d 178.0
3
3
(
COAdam), 171.0–169.6 (CH CO), 101.2 (C-1), 73.2
3
d 5.24 (d, 1H, H-4), 5.19 (dd, 1H, J2,3 10.4 Hz, H-2),
5.02 (dd, 1H, J3,4 3.4 Hz, H-3), 4.44 (d, 1H, J1,2
(
C-3), 72.2 (C-5), 71.7 (C-2), 69.8 (CH ), 68.8 (C-4),
2a
6
2
3.9 (CH ), 62.3 (C-6), 41.1, 39.2, 36.2, 28.3 (Adam),
2
7.9 Hz, H-1), 4.13–4.05 (m, 2H, CH ), 3.92, 3.49 (2m,
2d
d
6.3, 25.2 (CH , CH ), 21.1–20.9 (CH CO). Anal.
3
2H, CH ), 3.80 (m, 1H, J 6.4 Hz, H-5), 2.18–1.94
2a 5,6
2
b
2v
Calcd for C H O : C, 59.78; H, 7.27. Found: C,
2
(3s, 9H, CH CO), 2.17–1.71 (m, 15H, Adam), 2.03 (m,
3
9
42 12
5
9.71; H, 7.21.
2H, CH ), 1.91 (m, 2H, CH ), 1.23 (d, 2H, H-6);
2b 2v
1
3
C NMR (CDCl , 75.5 MHz): d 178.0 (COAdam),
3
3.19. 4-Adamantoyloxy-1-(a-D-glucopyranosyloxy)-
butane (20)
171.1–169.8 (CH CO), 101.5 (C-1), 71.8 (C-3), 70.7
(C-4), 69.5, 69.4 (C-2, C-5), 69.7 (CH ), 64.0 (CH ),
2a 2d
3
41.1, 39.0, 36.8, 28.3 (Adam), 26.4, 25.5 (CH ,
2b
A procedure similar to that for the preparation of 4 was
employed. Treatment of 19 (500 mg, 1.0 mmol) in
MeOH (1 mL) with NaOMe (5.5 mg, 0.1 mmol) gave
CH ), 21.1–21.0 (CH CO), 16.4 (C-6). Anal. Calcd
2v 3
for C H O : C, 61.47; H, 7.47. Found: C, 61.39; H,
9
2
42 11
7.40.

1468
C. Binkowski et al. / Carbohydrate Research 340 (2005) 1461–1468
3
(
.22. 4-Adamantoyloxy-1-(b-L-fucopyranosyloxy)butane
24)
4. Sandier, A.; Brown, W.; Mays, H. Langmuir 2000, 16,
1
. Moine, L.; Amiel, C.; Brown, W.; Guerin, P. Polym. Int.
2001, 50, 663–676.
. Auz e´ ly-Velty, R.; Rinaudo, M. Macromolecules 2002, 35,
634–1642.
5
6
A procedure similar to that for the preparation of 4 was
employed. Treatment of 23 (500 mg, 1.4 mmol) in
MeOH (5 mL) with NaOMe (6.2 mg, 0.14 mmol) gave
2
1
7955–7962.
7. Binello, A.; Cravotto, G.; Nano, G. M.; Spagliardi, P.
Flavour Flag. J. 2004, 19, 394–400.
8. David, C.; Millot, M.; Renard, E.; S e´ bille, B. J. Incl.
Phenom. 2002, 44, 369–372.
4 in 71% yield as an oil; IR; m 3370.0 (OH),
1 1
ꢀ
+•
723.3 cm
(COAdam); [M+Na]
1
m/z 421.5;
H
NMR (CDCl , 300 MHz): d H NMR (CDCl3,
3
3
9
. Ravoo, B. J.; Jacquier, J.-C.; Wenz, G. Angew. Chem., Int.
Ed. 2003, 42, 2066–2070.
00 MHz): d 4.19 (d, 1H, J1,2 7.2 Hz, H-1), 4.08–3.92
(
1
3
m, 2H, CH ), 3.92, 3.54 (2m, 2H, CH ), 3.72 (d,
H, J3,4 2.5 Hz, H-4), 3.61 (m, 1H, J2,3 10.1 Hz, H-2),
.60–3.51 (2m, 2H, H-3, H-5), 2.05–1.70 (m, 15H,
10. Pun, S. H.; Davis, M. E. Bioconjugate Chem. 2002, 13,
30–639.
2
a
2d
6
1
1. Garcia-Lopez, J. J.; Hernandez-Mateo, F.; Isac-Garcia, J.;
Kim, J. M.; Roy, R.; Santoyo-Gonz a´ lez, F.; Vargas-
Berenguel, A. J. Org. Chem. 1999, 64, 522–531.
Adam), 2.00, 1.88 (m, 4H, CH , CH ), 1.32 (d, 2H,
d
2
2v
1
3
H-6); C NMR (CDCl , 75.5 MHz): d 178.3 (COA-
dam), 103.4 (C-1), 74.4 (C-3), 72.0 (C-4), 71.7 (C-5),
7
2
Calcd for C H O : C, 62.30; H, 8.60. Found: C, 62.25;
H, 8.56.
12. Garc ´ı a-Barrientos, A.; Garcia-Lopez, J. J.; Isac-Garcia, J.;
Ortega-Caballero, F.; Uriel, C.; Vargas-Berenguel, A.;
Santoyo-Gonz a´ lez, F. Synthesis 2001, 1057–1064.
3
1.0 (C-2), 69.8 (CH ), 64.2 (CH ), 41.1, 39.2, 36.9,
2a 2d
1
3. Bellocq, N. C.; Pun, S. H.; Jensen, G. S.; Davis, M. E.
Bioconjugate Chem. 2003, 14, 1122–1132.
8.3 (Adam), 26.3, 25.8 (CH , CH ), 16.7 (C-6). Anal.
2
b
2v
2
1
34
7
1
4. Kida, T.; Ohe, T.; Higashimoto, H.; Harada, H.; Nak-
atsuji, Y.; Ikeda, I.; Akashi, M. Chem. Lett. 2004, 33, 258–
2
59.
1
5. Schmidt, R. R.; Wegmann, B.; Jung, K. H. Liebigs Ann.
Chem. 1991, 121–124.
Acknowledgements
1
6. Hu, X.; Chen, H.; Zhang, X. Angew. Chem., Int. Ed. 1999,
3
8, 3718–3720.
17. Schmidt, O. Methods Carbohydr. Chem. 1962, 2, 318–
25.
We thank the Minist e` re de la Recherche for financial
support and Professor J. Banoub for helpful discussions.
3
1
1
2
8. Collins, P. M.; Munasinghe, V. R. N. Carbohydrates;
University Press: London G.B., 1987.
9. Hanessian, S.; Banoub, J. Adv. Chem. Ser. 1976, 39, 36–
References
4
1.
0. Schneider, H. J.; Hacket, F.; R u¨ diger, V.; Ikeda, H. Chem.
Rev. 1998, 98, 1755–1786.
1
2
. Connors, K. A. J. Pharm. Sci. 1995, 84, 843–848.
. Eftink, M. R.; Andy, M. L.; Bystrom, K.; Perlmytter, H.
D.; Kristol, S. J. Am. Chem. Soc. 1989, 111, 6765–6772.
. Amiel, C.; S e´ bille, B. Adv. Colloid Interface Sci. 1999, 79,
21. Gil, V. M. S.; Oliveira, N. C. J. Chem. Educ. 1990, 67,
473–478.
22. Landy, D.; Fourmentin, S.; Salome, M.; Surpateanu, G. J.
Incl. Phenom. 2000, 38, 187–190.
3
105–122.