Synthesis of upper rim calix[4]arene divalent glycoclusters via amide bond conjugation

Article abstract of DOI:10.1016/j.tet.2004.11.048

Synthetic routes for linking two sugar units at the upper rim of cone calix[4]arenes, through the formation of amide bonds, have been explored. Steric effects prevent the coupling of calix[4]arene dicarboxylic acid with simple aminoglycosides, whereas the corresponding reaction with carbohydrates bearing a two or three carbon atoms spacer, terminating with a primary amino group, allows the synthesis of several difunctionalized calix[4]arene neoglycoconjugates, attractive in chemical glycobiology and supramolecular chemistry.

Full text of DOI:10.1016/j.tet.2004.11.048

Tetrahedron 61 (2005) 1149–1154
Synthesis of upper rim calix[4]arene divalent glycoclusters via
amide bond conjugation
*
Uta Sch a¨ del, Francesco Sansone, Alessandro Casnati and Rocco Ungaro
Dipartimento di Chimica Organica e Industriale, Universit a` degli Studi, Parco Area delle Scienze 17/A, I-43100 Parma, Italy
Received 20 August 2004; revised 28 October 2004; accepted 18 November 2004
Available online 15 December 2004
Abstract—Synthetic routes for linking two sugar units at the upper rim of cone calix[4]arenes, through the formation of amide bonds, have
been explored. Steric effects prevent the coupling of calix[4]arene dicarboxylic acid with simple aminoglycosides, whereas the
corresponding reaction with carbohydrates bearing a two or three carbon atoms spacer, terminating with a primary amino group, allows the
synthesis of several difunctionalized calix[4]arene neoglycoconjugates, attractive in chemical glycobiology and supramolecular chemistry.
q 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
paper the synthetic results obtained. An amide bond has
been used to synthesize lower rim calix[4]arene–mono-
saccharide conjugates, but to the best of our knowledge
the synthesis of upper rim derivatives has never been
reported.
1
3
Carbohydrate clusters are becoming interesting targets as
1
model systems for studying protein–sugar and sugar–
2
sugar interactions, which play a central role in glyco-
3
biology. Neoglycoconjugates based on cyclodextrin and
4
calixarene cores have been used for this purpose and they
are also attractive as potential molecular delivery systems.
5
2. Results and discussion
For this purpose, the presence of binding groups in addition
to the sugar units is useful in order to complex substrates to
be delivered to a specific target. In the case of calix[4]-
arenes, the sugar moieties were almost exclusively attached
at the lower or upper rim through the formation of ether
9
Reaction of the calix[4]arene diacid 1 with 2,3,4,6-tetra-O-
14
acetyl-b-D-galactosamine 2a and 2,3,4,6-tetra-O-acetyl-b-
14
D-glucosamine 2b in the presence of O-(benzotriazol-1-
0
0
yl)-N,N,N ,N -tetramethyluronium hexafluorophosphate
HBTU) and triethylamine (TEA) at rt (Scheme 1) did not
6
bonds or carbon–carbon bonds exploiting trimethylsilyl
(
7
a
7b
triflate and copper(II) triflate mediated glycosylation
reactions on bis- and tetrahydroxymethylcalix[4]arenes, a
Suzuki type reaction using calix[4]arene di- and mono-
give a glycosylated calixarene, but the benzotriazole ester 3,
which was isolated in yields higher than 70% and
characterized since it is quite stable. Heating compound 3
with these monosaccharides overnight in presence of an
excess of base in acetonitrile led to the complete
7
d
7c,e
boronic acid derivatives and Wittig reactions
on
formylated calix[4]arenes. Only a couple of examples of
thiourea containing glycocalixarenes are known where the
hydrogen bonding spacer is able to complex anionic
8
species. The dicarboxylic acid 1 is a well known cone
calix[4]arene intermediate and has been used for the
9
1
synthesis of cleft-like and macrobicyclic N-linked
0
11
1
2
peptidocalix[4]arenes and other molecular receptors. We
therefore explored the possibility of using compound 1 as a
starting material for the synthesis of novel upper rim
calix[4]arene glycoconjugates through amide bond for-
mation, where the amide group could be exploited for the
binding of acidic and/or basic substrates, and report in this
Keywords: Calix[4]arene; Neoglycoconjugates; Glycoside; Amide bond.
*
Corresponding author. Tel.: C39 0521 905412; fax: C39 0521 905472;
e-mail: rocco.ungaro@unipr.it
2 2
Scheme 1. (a) HBTU, TEA, CH Cl , rt, 5 h.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.11.048

1150
U. Sch a¨ del et al. / Tetrahedron 61 (2005) 1149–1154
decomposition of 3 without forming any coupling product
with glycosamines 2a,b. Similarly, when the acid chloride
4 was reacted with glycosylamines 2a,b using TEA as
base, the calix[4]arene acid 1 and the sugar were found after
aqueous work-up and no coupling product could be detected.
these compounds. In the case of glycocalixarenes 7a,b, the
aromatic protons of the unsubstituted aromatic rings
resonate at dw6.30 and those of the substituted ones at
dw7.35, thus confirming that these compounds exist mainly
in the open flattened cone conformation, in CDCl3.
1
1
Suspecting that failure in the coupling reaction between
a,b and 3 or 4 could be mainly ascribed to repulsive steric
2
interactions between the reacting partners, we decided to
introduce a spacer either on the calixarene or on the sugar
moiety. Nevertheless, the condensation reaction of calix[4]-
Figure 1. The two possible flattened cone conformers of a upper rim
difunctionalised tetrapropoxycalix[4]arene.
1
5
arene–acetic acid derivative 5 with galactosamine 2a was
unsuccessful in a variety of conditions. On the other hand,
the reaction of the calix[4]arene dicarboxylic acid 1 with the
Therefore, no intramolecular hydrogen bonding is taking
place between the two amide groups in compounds 7a,b
which could be ascribed to the intrinsic weakness of the
noncovalent interaction or to steric repulsion between
1
6
galactosamine derivative 6a, having a two methylene unit
spacer between the sugar moiety and the amine group, in the
presence of HBTU and an excess of base (pHO12) at 80 8C
in acetonitrile, led to the synthesis of the coupling product
1
the two protected sugar units. The H NMR spectra of the
deprotected glycocalixarenes 8a,b in the same solvent give
very broad signals, which tend to sharpen upon dilution,
thus indicating extensive intermolecular aggregation due to
7
a (Scheme 2). Comparable results were obtained using
glucosamine 6b as glycosyl donor to obtain 7b, and also
reacting at rt the two glycosylamines 6a and 6b with the
calixarene diacylchloride 4. Deprotection of 7a,b with
triethylamine in aqueous methanol gave the amide-linked
the large number of free OH groups. In CD OD, the spectra
3
show sharp signals instead. The relative position of the
signals of the aromatic protons in this solvent indicates
again a preference for the open flattened cone conformation
also for compounds 8a,b. Both for the protected and the
deprotected compounds 7a,b and 8a,b no splitting could be
observed for the signals of the ortho aromatic and of the
1
glycoconjugates 8a,b in 30–33% overall yield. The H
NMR spectra of derivatives 7a,b in CDCl show sharp
signals, which allow the exclusion of intermolecular
3
1
7
aggregation phenomena. It is well known that calix[4]ar-
enes difunctionalized at the upper rim with hydrogen
bonding donor and acceptor groups can experience
intramolecular H-bonding in apolar solvents, which stabil-
ize a closed flattened cone conformation (Fig. 1) with
respect to the open flattened cone conformation, which is
more stable in strong donor solvents. Usually, these
conformational preferences can be recognized very clearly
axial and equatorial protons of the calixarene Ar–CH –Ar
2
methylene bridge, which is indeed typical for other
calix[4]arene derivatives bearing chiral units at the upper
7
b,10,11
rim.
Evidently, because of the spacer, the carbo-
hydrate chiral units are too far away from the calixarene
skeleton to influence its NMR signals.
The second approach we investigated was the formation of
an amide bond with an amino acid spacer. This constitutes
an attractive route to build up a novel type of hybrid sugar–
peptidocalix[4]arene receptors to be used in the recognition
of biologically relevant substrates. We focused our attention
on aspartic acid as spacer, because of its wide use in natural
and synthetic peptides for the linkage of sugar units, and on
glucose as saccharide unit, because of its higher solubility in
water in comparison with other neutral monosaccharides,
which could lead to water soluble glycocalixarenes.
L-Aspartic acid dimethyl ester hydrochloride was then
reacted with the calix[4]arene diacid 1 giving 9 and, after
hydrolysis, 10 in moderate overall yields. The reaction of
compound 10 with glucosamine 2b in the presence of
HBTU (Scheme 3) gave a complex mixture of products in
which the sugar–peptide conjugate 11 was detected by ESI-
MS but could not be isolated. Significantly better results
were obtained through the alternative synthetic route
consisting in the condensation of the sugar–amino acid
derivative 13 with calix[4]arene dicarboxylic acid 1 or
diacylchloride 4 (Scheme 3). In these cases, the protected
1
by inspecting the aromatic region of the H NMR spectra of
3
Scheme 2. (a) 1, HBTU, TEA, CH CN, 80 8C, 12 h, 35–37%; (b) 4, TEA,
CH Cl , rt; (c) TEA, MeOH, H O, rt, 16 h, 96–98%.
2
2
2

U. Sch a¨ del et al. / Tetrahedron 61 (2005) 1149–1154
1151
sugar–peptidocalix[4]arene conjugate 14 was obtained in
8–72% yield and the full deprotection both from benzyl
4. Experimental
6
and acetyl groups with TEA in a 8/1 methanol/water
mixture easily occurred, leading to the isolation of the
glycopeptidocalix[4]arene 15 as bis triethylammonium salt.
All moisture sensitive reactions were carried out under
nitrogen atmosphere. All dry solvents were prepared
according to standard procedures and stored over molecular
sieves. Melting points were determined on an Electro-
thermal apparatus with samples in tubes sealed under
1
nitrogen atmosphere or on a Kofler apparatus. H NMR and
C NMR spectra were recorded on Bruker AC300 and
1
3
Bruker AMX400 spectrometers. Spectra are reported in
ppm downfield from TMS as internal standard. Mass spectra
by electrospray ionization (ESI) and chemical ionization
(CI) methods were recorded on a Micromass ZMD and on a
Finnigan Mat SSQ710 spectrometer, respectively. Elemen-
tal analyses were performed using a CHN 1106 Carlo Erba
instrument and are reported as percentage. Analytical TLC
was performed using Merck prepared plates (silica gel 60
F-254 on aluminum). Merck silica gel (40–63 mm) was used
for flash-chromatography. N-Boc-L-Asp-OBn was pur-
chased from Novabiochem. The calix[4]arene dicarboxylic
9
11
acid 1, the corresponding diacyl chloride 4, the 2,3,4,6-
1
4
tetra-O-acetyl-b-D-galacto- and b-D-glucosamine 2a,b and
the 2,3,4,6-tetra-O-acetyl-(2-aminoethyloxy)-b-D-galacto-
and b-D-glucoside 6a,b were synthesized according to
1
6
literature procedures.
4.1. General procedures for the coupling of amines with
carboxylic calix[4]arene derivatives
Scheme 3. (a) HBTU, TEA, CH
from 0 8C to rt, 6 h, 92%; (c) 2b, HBTU, TEA, CH
CF COOH, CH Cl , from 0 8C to rt, 2 h, quantitative; (e) 1, HBTU, TEA,
CH Cl , rt, 4 h, 72%; (f) 4, TEA, CH Cl , rt, 4 h, 68%; (g) TEA, MeOH,
O, rt, 16 h, Amberlite IR-120 resin, 95%.
2
Cl
2
, rt, 4 h, 64%; (b) LiOH, THF, H
2
O,
(
A) The amine and triethylamine (TEA) were added to a
2
2
Cl , rt, 12 h; (d)
suspension in dry methylene chloride of the calix[4]arene
dicarboxylic acid derivative. Then HBTU was added. The
reaction was stirred for 4 h at rt unless otherwise specified.
During the first 30 min, the pH-value was frequently
checked and TEA was added if necessary to keep pH at
3
2
2
2
2
2
2
H
2
The protected derivative 14 in CDCl exists in the open
3
flattened cone conformation and the corresponding depro-
tected glycocalix[4]arene 15 shows similar properties to
ca. 8.5. The reaction was quenched with a 5% NH
solution. The organic layer was separated, washed with 5%
NaHCO aqueous solution and water, dried over Na SO
4
4
Cl water
3
2
those described above for compounds 8a,b in CDCl and
3
CD OD. Titration of 15 with an aqueous solution of NaOH
3
and evaporated to dryness in vacuo. The crude was purified
by flash-chromatography on silica gel.
gave the corresponding sodium salt which shows good
solubility in water up to 1.4!10 M. The H NMR
spectrum in D O of this compound is rather broad indicating
2
K2
1
(B) A solution of calixarene diacylchloride 4, amine and
TEA in dry methylene chloride was stirred at rt for 4 h, then
extensive aggregation phenomena which are currently under
investigation.
the reaction was quenched by addition of a 5% NH Cl water
4
solution. The organic layer was separated, washed with 5%
NaHCO aqueous solution and water, dried over Na SO
4
3
2
and evaporated to dryness in vacuo. The crude was purified
by flash-chromatography on silica gel.
3. Conclusion
4.2. General procedure for the deprotection of the
glycocalixarenes from the acetyl groups
Several synthetic routes for linking two sugar units at the
upper rim of cone calix[4]arenes, through the formation of
amide bonds, have been investigated. Steric effects prevent
the coupling of calix[4]arene dicarboxylic acid with simple
aminoglycosides, whereas the corresponding reaction with
carbohydrates bearing a two or three carbon atoms spacer
terminating with a primary amino group was more
successful. This strategy allowed the synthesis of several
difunctionalized calix[4]arene neoglycoconjugates, attrac-
tive in chemical glycobiology and supramolecular
chemistry. The conformational properties of the compounds
(C) The protected glycocalixarene was treated with the
mixture methanol/water/TEA 8/1/1 at rt overnight. The
reaction was quenched by evaporation to dryness in vacuo,
then the residue was dissolved in methanol and treated with
Amberlite IR-120 resin until neutral pH. The resin was
filtered off and the solution was evaporated to dryness in
vacuo.
4.2.1. 5,17-Bis(benzotriazolyloxycarbonyl)-25,26,27,28-
tetra-n-propoxycalix[4]arene (3). This compound was
isolated as main product from the reaction of 5,17-
1
synthesized have been established by H NMR experiments
in different solvents.

1152
U. Sch a¨ del et al. / Tetrahedron 61 (2005) 1149–1154
bis(hydroxycarbonyl)-25,26,27,28-tetra-n-propoxycalix[4]-
arene (1) with 2,3,4,6-tetra-O-acetylgalactosamine (2a)
The crude product was chromatographed using as eluent the
mixture hexane/acetone from 1.5/1 to 1.2/1, v/v. Yield
0.10 g (35%); mp 136–138 8C; H NMR (300 MHz,
9
14
1
4
and with 2,3,4,6-tetra-O-acetylglucosamine (2b) accord-
1
ing to the reported general procedure A. White crystals;
yield 75–78%; mp 237–238 8C; H NMR (300 MHz,
CDCl ): dZ7.36 (s, 4H, Ar), 6.48 (t, JZ7.2 Hz, 2H, NH),
3
1
6.40–6.34 (m, 6H, Ar), 5.23 (t, JZ9.6 Hz, 2H, H-3), 5.09 (t,
JZ9.9 Hz, 2H, H-4) 5.02 (dd, JZ9.9, 8.4 Hz, 2H, H-2),
4.55 (d, JZ8.4 Hz, 2H, H-1), 4.46 (d, JZ13.2 Hz, 4H, Hax
CDCl ): d 8.01 (dd, JZ8.0, 1.0 Hz, 2H, Ar), 7.89 (s, 4H,
3
Ar), 7.39 (m , 6H, Ar), 6.52 (t, JZ6.0 Hz, 2H, Ar), 6.44 (d,
c
JZ6.0 Hz, 4H, Ar), 4.55 (d, JZ13.5 Hz, 4H, Hax of
ArCH Ar), 4.14 (t, JZ7.7 Hz, 4H, OCH CH CH ), 3.81
of ArCH Ar), 4.27 (dd, JZ12.6, 5.1 Hz, H2, H-6), 4.14 (dd,
2
0
NH and OCH CH CH ), 3.80–3.67 (m, 10H, OCHHCH -
JZ12.6, 2.1 Hz, H2, H-6 ), 4.02–3.95 (m, 6H, OCHHCH -
2
2
2
3
2
(
Heq of ArCH Ar), 1.96 (m , 8H, OCH CH CH ), 1.09 (t,
t, JZ7.1 Hz, 4H, OCH CH CH ), 3.34 (d, JZ13.6 Hz, 4H,
2
2
3
2
2
3
2
NH, OCH CH CH , H-5 and OCH CHHNH), 3.62–3.50
2 2 3 2
2
c
2
2
3
JZ7.4 Hz, 6H, OCH CH CH ), 1.01 (t, JZ7.4 Hz, 6H,
(m, 2H, OCH CHHNH), 3.23 (d, JZ13.2 Hz, 4H, H of Ar
CH Ar), 2.07 (s, 3H, CH CO), 2.04 (s, 3H, CH CO), 2.01 (s,
2 3 3
2
2
3
2 eq
1
3
OCH CH CH ); C NMR (75 MHz, CDCl ): d 164.0,
2
2
3
3
1
1
62.7 (C]O, C ), 155.5, 143.4, 137.3, 132.9, 131.4, 128.4,
ar
28.2, 124.6, 122.7, 120.1, 117.9, 108.4 (C ), 77.14, 77.09
ar
3H, CH CO), 1.98–1.88 (m, 8H, OCH CH CH ), 1.92 (s,
3 2 2 3
3H, CH CO), 1.06 (t, JZ7.5 Hz, 6H, OCH CH CH ), 0.95
3 2 2 3
13
(t, JZ7.5 Hz, 6H, OCH CH CH ); C NMR (75 MHz,
2 2 3
(
OCH CH CH ), 30.9 (ArCH Ar), 23.3 (OCH CH CH ),
2
2
2
3
2
2
3
1
0.5, 10.0 (OCH CH CH ); ESI-MS for C H N O
6
CDCl ): d Z170.6, 170.1, 169.4 and 167.7 (C]O), 160.4,
2
2
3
C
54 54
8
3
C
(
914.40): m/z 937.5 [M CNa] . Anal. Calcd for
155.6, 136.3, 133.3, 128.0, 127.8, 127.4 and 122.3 (Car),
100.9 (C-1), 77.0 and 76.6 (OCH CH CH ), 72.6, 71.9, 71.3
C H N O : C, 70.88; H, 5.95; N, 9.18. Found C, 70.85;
5
4
54
6
8
2
2
3
H, 5.96; N, 9.21.
and 68.3 (C-2, C-3, C-4, C-5), 69.1 (C-6), 61.8 (NHCH2-
CH O), 39.5 (NHCH CH O), 30.9 (ArCH Ar), 23.3 and
2
2
2
2
4
.2.2. 5,17-Bis[(2,3,4,6-tetra-O-acetyl-b-D-galacto-
23.1 (OCH
2
CH
CH
m/z 1449.6 [MCNa] . Anal. Calcd for C74
2
CH
3
), 20.7 and 20.6 (CH
); ESI-MS for C74H N O
94 2
3
CO), 10.5 and
26 (1426.61):
26: C,
pyranosyloxyethylamino)carbonyl]-25,26,27,28-tetra-n-
propoxycalix[4]arene (7a). 2,3,4,6-Tetra-O-acetyl-(2-
aminoethyloxy)-b-D-galactoside (6a) (0.61 g, 1.55 mmol)
and compound 1 (0.26 g, 0.39 mmol) were reacted in
presence of HBTU (0.43 g, 0.94 mmol) and TEA (1.00 mL,
10.0 (OCH
2
2
CH
3
C
H N O
94 2
1
6
62.26; H, 6.64; N, 1.96. Found C, 62.30; H, 6.63; N, 1.99.
4.2.4. 5,17-Bis[(b-D-galactopyranosyloxyethylamino)car-
bonyl]-25,26,27,28-tetra-n-propoxycalix[4]arene (8a).
The compound was obtained following the general
7
.64 mmol) following the general procedure A but using dry
acetonitrile (20 mL) as solvent. In this case, the reaction was
also heated to reflux overnight. Alternatively, 2,3,4,6-tetra-
procedure C. Colorless crystals; yield 96%; mp 148–
1
6
1
O-acetyl-(2-aminoethyloxy)-b-D-galactoside (6a) (0.60 g,
.53 mmol) and compound 4 (0.28 g, 0.39 mmol) were
149 8C; H NMR (300 MHz, CD OD): dZ7.57 (s, 4H,
3
1
Ar), 6.30 (bs, 6H, Ar), 4.52 (d, JZ13.2 Hz, 4H, Hax of
reacted in presence of TEA (0.2 mL, 1.53 mmol) following
procedure B. The crude product was chromatographed with
ethyl acetate. Light yellow oil; yield 0.19 g (37%); H NMR
ArCH Ar), 4.33 (d, JZ7.4 Hz, 2H, H-1), 4.09 (t, JZ7.2 Hz,
2
4H, OCH CH CH ), 3.87 (d, JZ2.4 Hz, 2H, H-4), 3.88–
2
2
3
1
3.66 (m, 18H, H-2, H-3, H-5, H-6, OCH CH CH ), 3.66–
3.50 (m, 8H, C(O)NHCH CH ), 3.27 (d, JZ13.2 Hz, 4H,
2 2
2 2 3
(
300 MHz, CDCl ): dZ7.36 (s, 4H, Ar), 6.51–6.39 (m, 4H,
3
Ar, NH), 6.38–6.27 (m, 4H, Ar), 5.38 (d, JZ3.4 Hz, 2H,
H-4), 5.20 (dd, JZ10.5, 7.9 Hz, 2H, H-2), 5.02 (dd, JZ
Heq of ArCH Ar), 1.97 (m , 8H, OCH CH CH ), 1.14 (t,
2 c 2 2 3
JZ7.4 Hz, 6H, OCH CH CH ), 0.97 (t, JZ7.4 Hz, 6H,
2
2
3
1
3
1
0.5, 3.4 Hz, 2H, H-3), 4.50 (d, JZ7.8 Hz, 2H, H-1), 4.45
OCH CH CH ); C NMR (75 MHz, CD OD): dZ170.8
2 2 3 3
(
H-6,6 ), 4.03–3.85 (m, 6H, H-5, OCH CH CH ), 3.80–3.63
d, JZ13.4 Hz, 4H, Hax of ArCH Ar), 4.15–4.04 (m, 4H,
(C]O), 162.3, 157.0, 138.2, 134.5, 129.5, 129.4, 129.2,
123.7 (C ), 105.5 (C-1), 78.4, 75.2, 72.9, 70.6, 70.0, 62.8
2
0
m, 8H, C(O)NHCH CH , OCH CH CH ), 3.63–3.45 (m,
2
2
3
ar
(
(C-2, C-3, C-4, C-5, C-6, NHCH CH O), 78.3, 77.0
2
2
2
2
2
3
2
4
ArCH Ar), 2.13, 2.02, 1.97, 1.89 (4s, 6H each, C(O)CH ),
H, C(O)NHCH CH ), 3.21 (d, JZ13.4 Hz, 4H, H of
(OCH CH CH ), 41.5 (C(O)NHCH CH ), 32.0 (ArCH Ar),
2 2 3 2 2 2
24.9, 24.7 (OCH CH CH ), 11.6, 10.7 (OCH CH CH );
2 2 3 2 2 3
2
2
eq
2
3
2
7
.01–1.82 (2m, 4H each, OCH CH CH ), 1.04 (t, JZ
ESI-MS for C H N O (1090.52): m/z 1112.8 [MC
58 78 2 18
Na] . Anal. Calcd for C H N O : C, 63.84; H, 7.20; N,
58 78 2 18
2.57. Found C, 63.88; H, 7.22; N, 2.54.
2
2
3
C
.4 Hz, 6H, OCH CH CH ), 0.92 (t, JZ7.5 Hz, 6H,
2
2
3
1
3
OCH CH CH ); C NMR (75 MHz, CDCl ): dZ170.3,
2
2
3
3
1
70.2, 170.1, 170.0, 169.6 (C(O)NH, C(O)CH ), 160.5,
3
1
55.8, 135.9, 133.5, 128.1, 128.0, 127.7, 122.3 (C ), 101.4
ar
4.2.5. 5,17-Bis[(b-D-glucopyranosyloxyethylamino)car-
bonyl]-25,26,27,28-tetra-n-propoxycalix[4]arene (8b).
(
C-1), 76.8, 76.6 (OCH CH CH ), 70.8, 70.7, 68.9, 68.0,
2
2
3
1
6
6.9, 61.2 (C-2, C-3, C-4, C-5, C-6, NHCH CH O), 39.5
2
General procedure C. Yield 97%; mp 185–187 8C;
H
2
(
NHCH CH O), 30.9 (ArCH Ar), 23.3, 23.25, 23.20, 23.1
2
NMR (300 MHz, CD OD): dZ7.52 (s, 4H, Ar), 6.32–6.26
2
2
3
(
CH CH ); ESI-MS for C H N O (1426.61): m/z 1449.6
OCH CH CH ), 20.5, 20.4 (C(O)CH ), 10.4, 10.0 (OCH -
(m, 6H, Ar), 4.49 (d, JZ13.2 Hz, 4H, Hax of ArCH Ar),
2
2
3
3
2
2
2
3
74 94 2 26
4.34 (d, JZ7.8 Hz, 2H, H-1), 4.08 (t, JZ7.6 Hz, 4H,
OCH CH CH ), 4.09–4.00 (m, 2H, NHCH CHHO), 3.86
C
[
MCNa] . Anal. Calcd for C H N O : C, 62.26; H,
74 94 2 26
2
2
3
2
0
6
.64; N, 1.96. Found C, 62.30; H, 6.63; N, 1.99.
(d, JZ10.8 Hz, 4H, H-6 and H-6 ), 3.81–3.60 (m, 10H,
NHCH CHHO, OCH CH CH , NHCHHCH O and H-5),
3.59–3.49 (m, 2H, NHCHHCH O), 3.43–3.20 (m, 10H,
2
2
2
3
2
4
.2.3. 5,17-Bis[(2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
2
syloxyethylamino)carbonyl]-25,26,27,28-tetra-n-pro-
poxycalix[4]arene (7b). The compound was obtained
following the general procedure B starting from calixarene
H-3, H-4, H-2 and Heq of ArCH Ar), 2.02–1.85 (m, 8H,
2
OCH CH CH ), 1.11 (t, JZ7.5 Hz, 6H, OCH CH CH ),
2
2
3
2
2
3
1
3
0.95 (t, JZ7.2 Hz, 6H, OCH CH CH );
C NMR
2
2
3
1
1
16
4 (0.15 g, 0.21 mmol) and glucoside 6b (0.33 g,
.84 mmol) in presence of TEA (0.12 mL, 0.84 mmol).
(75 MHz, CD OD): dZ170.5 (C]O), 161.9, 156.7,
3
0
137.8, 134.3, 129.1 and 123.4 (C ), 104.6 (C-1), 78.1
ar

U. Sch a¨ del et al. / Tetrahedron 61 (2005) 1149–1154
1153
1
1.76 g (75%). The compound was identified by H and
13
(
6
(
OCH CH CH ), 77.9, 75.1 and 71.6 (C-2, C-3, C-4, C-5),
3
C
2
2
1
8
9.6 (C-6), 62.7 (NHCH CH O), 41.1 (NHCH CH O), 31.9
2
NMR and by ESI mass spectrometry: for C H N O
30 40 2 14
2
2
2
C C
(652.68): m/z 675.2 [MCNa] , 1327.7 [2MCNa] .
ArCH Ar), 24.6 and 24.4 (OCH CH CH ), 11.2, 10.5
2
2
2
3
(
OCH CH CH ); ESI-MS for C H N O (1090.52): m/z
2 2 3 58 78 2 18
C
112.8 [MCNa] . Anal. Calcd for C H N O : C, 63.84;
1
H, 7.20; N, 2.57. Found C, 63.88; H, 7.22; N, 2.54.
4.2.8. 4-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl-
amino)-L-aspartic acid 1-benzyl ester$CF COOH (13).
A solution of N-Boc-4-(2,3,4,6-tetra-O-acetyl-b-D-gluco-
5
8 78 2 18
3
1
8
4.2.6. 5,17-Bis(N-L-aspartylcarbonyl)-25,26,27,28-tetra-
n-propoxycalix[4]arene (10). The general coupling pro-
pyranosylamino)-L-aspartic acid 1-benzyl ester (1.50 g,
2.24 mmol) in CH Cl (25 mL) was cooled with ice-bath
2
2
cedure A was used with aspartic acid dimethyl ester
hydrochloride (0.31 g, 1.55 mmol) and dicarboxylic acid
and TFA (2.5 mL) was added. The reaction proceeded
without bath for 1 h, then was quenched by evaporation of
the organic solvent and by removing the excess of TFA
9
1
0
(0.26 g, 0.39 mmol) in presence of HBTU (0.43 g,
.94 mmol) and TEA (0.44 mL, 3.12 mmol). The crude
under high vacuum. The compound was then used without
1
product was chromatographed using as eluent the mixture
hexane/ethyl acetate 1/1 (v/v). Selected data for 5,17-
bis(dimethoxy-L-aspartylcarbonyl)-25,26,27,28-tetra-n-pro-
further purification. H NMR (300 MHz, CDCl ): dZ8.15
3
C
(bs, 3H, NH ) 7.53 (d, JZ9.3 Hz, 1H, NHCO), 7.45–7.27
3
(m, 2H, Ar), 7.33 (t, JZ7.5 Hz, 1H, Ar), 7.22 (d, JZ7.5 Hz,
2H, Ar), 5.38 (t, JZ9.3 Hz, 1H, H-3), 5.30–5.20 (m, 3H,
poxycalix[4]arene (9): colorless solid; yield 0.24 g (64%);
H NMR (300 MHz, CDCl ): dZ7.50 (d, JZ2.0 Hz, 2H,
1
CH Ph and H-1), 5.16 (t, JZ9.3 Hz, 1H, H-4), 5.01 (t, JZ
3
2
Ar), 7.46 (d, JZ2.1 Hz, 2H, Ar), 7.20 (d, JZ7.8 Hz, 2H,
NH), 6.30–6.22 (m, 2H, Ar), 6.21–6.15 (m, 4H, Ar), 5.09–
9.3 Hz, 1H, H-2 , 4.48 (bs, 1H, CHCH ), 4.29 (dd, JZ12.4,
4.3 Hz, 1H, H-6), 4.22 (dd, JZ12.4, 6.4 Hz, 1H, H-6 ), 3.85
)
2
0
(bd, 1H, H-5), 3.18 (bs, 2H, CHCH ), 2.09, 2.08 and 1.99
4
.98 (m, 2H, NHCHCH ), 4.42 (d, JZ13.4 Hz, 4H, H of
2
ax
2
1
3
ArCH Ar), 4.04 (t, JZ7.9 Hz, 4H, OCH CH CH ), 3.76 (s,
(3s, 12H, OCCH3); C NMR (75 MHz, CDCl ): dZ172.3,
2
2
2
3
3
6
H, OCH ), 3.68 (s, 6H, OCH ) 3.66 (t, JZ8.1 Hz, 4H,
171.5, 171.0, 170.8, 170.5, 167.6 (CO), 160.3 (q, JZ40 Hz,
CF CO), 137.8, 129.1, 129.0, 128.7, 128.3, 128.2 (C ),
3
3
OCH CH CH ), 3.22 (d, JZ13.5 Hz, 4H, H of ArCH Ar),
2
2
3
eq
2
3
ar
3
.12 (dd, JZ17.2, 4.4 Hz, 2H, NHCHCH ), 2.99 (dd, JZ
115.1 (q, JZ285 Hz, CF CO), 78.0, 73.5, 70.5, 69.1, 68.3,
2
3
1
7.2, 4.8 Hz, 2H, NHCHCH ), 1.95–1.80 (m, 8H, OCH -
62.0 (C-1, C-2, C-3, C-4, C-5, C-6), 72.9 (OCH Ph), 50.2
(CHCH ), 33.6 (CHCH ), 20.3 and 19.9 (CH CO); ESI-MS
2
2
2
CH CH ), 1.05 (t, JZ7.5 Hz, 6H, OCH CH CH ), 0.88 (t,
JZ7.5 Hz, 6H, OCH CH CH ); ESI-MS for C H N O
2
3
2
2
3
2
2
3
C
for C H N O (552.2): m/z 553.2 [MCH] , 575.2 [MC
25 32 2 12
2
2
3
C
54 66
2
14
C
Na] , 1105.6 [2MCH] , 1127.5 [2MCNa] .
C
C
(
966.45): m/z 989.6 [MCNa] . A solution of compound 9
(
0.088 g, 0.09 mmol) in THF (10 mL) was cooled to 0 8C.
After addition of lithium hydroxide (0.008 g, 0.36 mmol)
dissolved in water (3 mL), the mixture was stirred at rt for
4.2.9. 5,17-Bis[(4-(2,3,4,6-tetra-O-acetyl-b-D-gluco-
pyranosylamino)-1-benzyloxyaspartyl)carbonyl]-25,26,
27,28-tetra-n-propoxycalix[4]arene (14). The glyco-
peptidocalixarene 14 was obtained from 1 (0.1 g,
0.15 mmol) and 13 (0.4 g, 0.6 mmol) in presence of TEA
(0.17 mL, 1.2 mmol) following the general procedure A
(yield 0.19 g, 72%) or from 4 (0.11 g, 0.15 mmol) following
the general procedure B (yield 0.18 g, 68%). Eluent for
6 h. The reaction was quenched by evaporation of the
organic solvent and subsequent addition of 1 N HCl until
acidic pH. Product 10 precipitated as white solid and was
filtered and dried. Colorless solid; yield 0.075 g (92%); mp
1
42–143 8C; H NMR (300 MHz, CDCl /CD OD 1/10,
1
3
3
v/v): dZ7.60 (bs, 4H, Ar), 6.28–6.12 (m, 6H, Ar), 4.97 (bs,
H, NHCHCH ), 4.47 (d, JZ13.2 Hz, 4H, H of ArCH2-
1
2
flash-chromatography: CH Cl /MeOH 30/1, v/v). H NMR
2
2
ax
2
Ar), 4.10 (t, JZ7.1 Hz, 4H, OCH CH CH ), 3.69 (t, JZ
(300 MHz, CDCl ) dZ7.52 (d, JZ1.8 Hz, 2H, ArCO), 7.50
2
2
3
3
6
.7 Hz, 4H, OCH CH CH ), 3.22 (d, JZ13.2 Hz, 4H, H
(d, JZ1.8 Hz, 2H, ArCO), 7.47 (d, JZ7.2 Hz, 2H,
ArCONH), 7.38–7.30 (m, 10H, Bn), 6.77 (d, JZ9.3 Hz,
2H, NHCOCH), 6.25–6.23 (m, 2H, Ar), 6.16–6.09 (m, 4H,
Ar), 5.32 (t, JZ9.3 Hz, 2H, H-3), 5.25–5.21 (m, 6H, H-1
2
2
3
eq
of ArCH Ar), 3.00 (d, JZ5.3 Hz, 4H, NHCHCH ), 2.01–
2
2
1
.84 (m, 8H, OCH CH CH ), 1.10 (t, JZ7.4 Hz, 6H,
2 2 3
OCH CH CH ), 0.91 (t, JZ7.4 Hz, 6H, OCH CH CH );
2
2
3
2
2
3
1
3
C NMR (75 MHz, CD OD): dZ174.8, 162.7 (CO), 156.6,
and PhCH ), 5.15–5.05 (m, 2H, NHCHCO), 5.08 (t, JZ
3
2
1
38.5, 134.2, 129.7, 129.6, 129.3, 123.7 (C ), 78.5, 78.2
9.3 Hz, 2H, H-4), 4.96 (t, JZ9.3 Hz, 2H, H-2), 4.43 (d, JZ
ar
(
3
OCH CH CH ), 51.3 (NHCHCH ), 37.4 (NHCHCH ),
2
13.5 Hz, 4H, Hax of ArCH Ar), 4.27 (dd, JZ12.3, 4.2 Hz,
2
3
2
2
2
0
2.2 (ArCH Ar), 24.9, 24.7 (OCH CH CH ), 11.6, 10.6
2
2H, H-6), 4.10–4.00 (m, 6H, H-6 and OCH CH CH ),
2
2
3
2
2
3
(
OCH CH CH ); ES-MS for C H N O (910.39): m/z
2
3.84–3.78 (m, 2H, H-5), 3.68 (t, JZ6.9 Hz, 4H, OCH CH -
CH ), 3.22 (d, JZ13.5 Hz, 2H, H of ArCH Ar), 3.20 (d,
3 eq 2
2
3
50 58
2
14
2 2
K
67.9 [MKHCNaCCl] . Anal. Calcd for C H N O :
9
C, 65.92; H, 6.42; N, 3.07. Found C, 65.89; H, 6.46; N, 3.10.
5
0
58
2
14
JZ13.5 Hz, 2H, Heq of ArCH Ar), 3.04 (dd, JZ15.6,
2
3.9 Hz, 2H, CHCHH), 2.89 (dd, JZ15.6, 4.2 Hz, 2H,
4.2.7. N-Boc-4-(2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
sylamino)-L-aspartic acid 1-benzyl ester (12). Glucosa-
CHCHH) 2.03–1.82 (m, 32H, CH CO and OCH CH CH ),
1.10 (t, JZ7.5 Hz, 6H, OCH CH CH ), 0.90 (t, JZ7.8 Hz,
3
2
2
3
2
2
3
1
4
mine 2b (1.5 g, 4.32 mmol) and N-Boc-L-Asp-OBn
13
6H, OCH CH CH ); C NMR (75 MHz, CDCl ) dZ171.2,
2 2 3 3
(
(
1.16 g, 3.60 mmol) were reacted in presence of HBTU
3.0 g, 7.91 mmol) and TEA (1.10 mL, 7.91 mmol) in dry
171.1, 170.6, 169.9, 169.5 and 167.2 (C]O), 161.4, 155.2,
137.1, 137.1, 135.4, 132.6, 128.6, 128.4, 128.0, 127.9,
127.8, 126.9 and 122.3 (C ), 78.2 and 77.1 (OCH CH -
CH Cl (30 mL) at rt for 1 h then the reaction was quenched
2
2
ar
2
2
by addition of a 5% NaHCO aqueous solution (20 mL).
3
CH ), 76.7, 73.7, 72.7, 70.5, 68.0 (C-1, C-2, C-3, C-4, C-5),
3
The organic phase was separated, washed with water and
evaporated to dryness in vacuo. The compound was
obtained pure as colorless solid by flash-chromatography
on silica gel (eluent: ethyl acetate/hexane 1/1, v/v). Yield
67.4 (PhCH ), 61.6 (C-6), 49.2 (CHCH ), 37.3 (CHCH ),
2
2
2
30.9 (ArCH Ar), 23.5 and 23.1 (OCH CH CH ), 20.7, 20.6
2
2
2
3
and 20.5 (CH CO), 10.8 and 9.9 (OCH CH CH ); ESI-MS
3
2
2
3
2C
for C H N O (1748.7): m/z 897.8 [MC2Na] , 1771.9
9
2 108 4 30

1154
U. Sch a¨ del et al. / Tetrahedron 61 (2005) 1149–1154
C
MCNa] . Anal. Calcd for C H N O : C, 63.15; H,
[
2. Rojo, J.; Morales, J. C.; Penad e´ s, S. Top. Curr. Chem. 2002,
218, 45–92.
9
2 108 4 30
6
.22; N, 3.20. Found C, 63.21; H, 6.15; N, 3.06.
3
. Bertozzi, C. R.; Kiessling, L. L. Science 2001, 2357–2364.
. Fulton, D. A.; Stoddart, J. F. Bioconj. Chem. 2001, 12,
4
4
.2.10. 5,17-Bis[(4-(b-D-glucopyranosylamino)-1-aspar-
6
55–672.
tyl)carbonyl]-25,26,27,28-tetra-n-propoxycalix[4]arene
15). Calixarene 14 was reacted following the general
procedure C. In this case, the yellowish oil obtained was
5
. (a) Aoyama, Y.; Matsuda, Y.; Chuleeraruk, J.; Nishiyama, K.;
Fujimoto, K.; Fujimoto, T.; Shimizu, T.; Hayashida, O. Pure
Appl. Chem. 1998, 70, 2379–2384. (b) Fujimoto, K.; Miyata,
T.; Aoyama, Y. J. Am. Chem. Soc. 2000, 122, 3558–3559.
. (a) Marra, A.; Scherrmann, M.-C.; Dondoni, A.; Casnati, A.;
Minari, P.; Ungaro, R. Angew. Chem., Int. Ed. Engl. 1994, 33,
(
triturated with Et O to obtain a white solid corresponding to
2
1
the bis triethylammonium salt of 15 [ H NMR (300 MHz,
6
MeOD) dZ7.70 (s, 4H, Ar), 6.25–6.12 (bs, 6H, Ar), 5.00–
4
.85 (m, 4H, H-1 and CHCH ), 4.53 (d, JZ13.5 Hz, 4H, Hax
2
2
479–2481. (b) Meunier, S. J.; Roy, R. Tetrahedron Lett.
996, 37, 5469–5472. (c) Roy, R.; Kim, J. M. Angew. Chem.,
of ArCH Ar), 4.16 (t, JZ8.1 Hz, 4H, OCH CH CH ),
3
2
2
2
3
0
.87–3.60 (m, 10H, H-6,6 , H-5, OCH CH CH ), 3.45–3.28
2 2 3
1
Int. Ed. 1999, 38, 369–372. (d) Saitz-Barria, C.; Torres-Pi-
nedo, A.; Santoyo-Gonz a´ lez, F. Synlett 1999, 12, 1891–1894.
(
1
(
m, 8H, H-4, H-2, Heq of ArCH Ar), 3.15 (q, JZ7.5 Hz,
2H, HNCH CH ), 2.95–2.77 (m, 4H, CHCH ), 2.08–1.88
2 3 2
2
(
e) Budka, J.; Tkadlecov a´ , M.; Lhot a´ k, P.; Stibor, I.
m, 8H, OCH CH CH ),1.32 (t, JZ7.5 Hz, 18H, HNCH -
2 2 3 2
Tetrahedron 2000, 56, 1883–1887. (f) Dondoni, A.; Hu, X.;
Marra, A.; Banks, H. D. Tetrahedron Lett. 2001, 42,
CH ), 1.17 (t, JZ8.1 Hz, 6H, OCH CH CH ), 0.95 (t, JZ
8
3
2
2
3
1
.1 Hz, 6H, OCH CH CH ); C NMR (75 MHz, MeOD)
3
2 2 3
3
295–3298.
. (a) Marra, A.; Dondoni, A.; Sansone, F. J. Org. Chem. 1996,
1, 5155–5158. (b) Dondoni, A.; Marra, A.; Scherrmann,
M.-C.; Casnati, A.; Sansone, F.; Ungaro, R. Chem. Eur. J.
997, 3, 1774–1782. (c) Dondoni, A.; Kleban, M.; Marra, A.
dZ177.4, 174.5 and 169.5 (C]O), 162.3, 156.5, 138.3,
7
1
33.9, 129.3, 129.0 and 123.4 (Ar), 81.3, 79.7, 78.9, 74.3,
1.6 (C-1, C-2, C-3, C-4, C-5), 78.2 and 77.9 (OCH CH -
6
7
CH ), 62.9 (C-6), 53.5 (CHCH ), 47.8 (HNCH CH ), 40.5
2
2
3
2
2
3
1
(
CHCH ), 32.0 (ArCH Ar), 24.7 and 24.4 (OCH CH CH ),
2 2 2 2 3
Tetrahedron Lett. 1997, 38, 7801–7804. (d) F e´ lix, C.;
Parrot-Lopez, H.; Kalchenko, V.; Coleman, A. W.
Tetrahedron Lett. 1998, 39, 9171–9174. (e) Dondoni, A.;
Kleban, M.; Hu, X.; Marra, A.; Banks, H. D. J. Org. Chem.
1
was subsequently dissolved in methanol and treated with
1.4 and 10.4 (OCH CH CH ), 9.3 (HNCH CH )]. This
2 2 3 2 3
Amberlite IR-120 resin, to give the neutral product 15.
Yield 0.10 g (96%); mp 177 (dec.); nmax/cm (KBr) 1727,
K1
1
2
002, 67, 4722–4733.
1
Ar), 6.32–6.17 (m, 6H, Ar), 5.00–4.85 (m, 4H, CHCH and
645 (CO); H NMR (300 MHz, MeOD) dZ7.61 (bs, 4H,
8
. Sansone, F.; Casnati, A.; Chierici, E.; Ungaro, R. Org. Biomol.
Chem. 2003, 1, 1802–1809.
2
H-1), 4.49 (d, JZ13.2 Hz, 4H, Hax of ArCH Ar), 4.12 (t,
2
9
. Arduini, A.; Fabbi, M.; Mirone, L.; Pochini, A.; Secchi, A.;
Ungaro, R. J. Org. Chem. 1995, 69, 1454–1457.
0. (a) Sansone, F.; Barboso, S.; Casnati, A.; Fabbi, M.; Pochini,
JZ7.8 Hz, 4H, OCH CH CH ), 3.78 (d, JZ12.3 Hz, 2H,
2
2
3
H-6), 3.70 (t, JZ6.4 Hz, 4H, OCH CH CH ), 3.60 (dd, JZ
2
2
3
0
1
1
2.3, 4.8 Hz, 2H, H-6 ), 3.42–3.23 (m, 8H, H-4, H-5, H-3
A.; Ugozzoli, F.; Ungaro, R. Eur. J. Org. Chem. 1998,
8
and H-2), 3.24 (d, JZ13.2 Hz, 4H, Heq of ArCH Ar), 3.03–
2
97–905. (b) Sansone, F.; Barboso, S.; Casnati, A.; Sciotto, D.;
2
1
6
1
1
6
.96 (m, 4H, CHCH ), 2.05–1.85 (m, 8H, OCH CH CH ),
.13 (t, JZ7.2 Hz, 6H, OCH CH CH ), 0.93 (JZ7.5 Hz,
2 2 2 3
Ungaro, R. Tetrahedron Lett. 1999, 40, 4741–4744.
1. Casnati, A.; Di Modugno, E.; Fabbi, M.; Pelizzi, N.; Pochini,
A.; Sansone, F.; Tarzia, G.; Ungaro, R. Bioorg. Med. Chem.
Lett. 1996, 6, 2699–2704.
2. Miyaji, H.; Dudi cˇ , M.; Tucker, J. H. R.; Prokes, I.; Light,
M. E.; Hursthouse, M. B.; Stibor, I.; Lhot a´ k, P. Tetrahedron
Lett. 2002, 43, 873–878.
2
2
3
1
3
1
1
1
1
H, OCH CH CH ); C NMR (75 MHz, MeOD) dZ173.7,
2
2
3
73.4 and 170.0 (CO), 162.4, 156.6, 138.2, 134.0, 129.3,
29.1, 128.4 and 123.4 (C ), 81.1, 79.7, 79.0, 73.9, 71.4 and
2.7 (C-1, C-2, C-3, C-4, C-5, C-6), 78.2 and 78.0
ar
(
OCH CH CH ), 51.1 (CHCH ), 38.3 (CHCH ) 31.9
2 2 3 2 2
(
ArCH Ar), 24.5 and 24.4 (OCH CH CH ), 11.3 and 10.4
2 2 2 3
3. (a) Roy, R.; Kim, J. M. Angew. Chem., Int. Ed. 1999, 38,
(
OCH CH CH ); ESI-MS for C H N O 1232.5): m/z
2 2 3 62 80 4 22
2
61.53 [MK2HC4Na] , 1299.7 [MK2HC3Na] . Anal.
C
C
3
69–372. (b) Budka, J.; Tkadlecov a´ , M.; Lhot a´ k, P.; Stibor, I.
Tetrahedron 2000, 56, 1883–1887.
6
Calcd for C H N O : C, 60.38; H, 6.54; N, 4.54. Found
C, 60.23; H, 6.39; N, 4.50.
6
2 80 4 22
4. Vansteenkiste, S.; Schacht, E.; Haro, I.; Reig, F.; Parente, A.;
Garcia-Anton, J. M. Bull. Soc. Chim. Belg. 1991, 100,
7
59–766.
5. Gutsche, C. D.; Sharma, S. K.; Kanamathareddy, S. Synthesis
997, 1268–1272.
1
1
1
Acknowledgements
1
6. Sasaki, A.; Murahashi, N.; Yamada, H.; Morikawa, A. Biol.
Pharm. Bull. 1995, 18, 740–746.
This work was partially supported by M.I.U.R. (COFIN
002, ‘Calixarene Glycoconjugates’ Project) and EU (TMR
grant FMRX-CT98-0231). The authors thank the Centro
Interdipartimentale Misure of Parma University for NMR
and MS facilities.
2
7. (a) Scheerder, J.; Vreekamp, R. H.; Engbersen, J. F. J.;
Verboom, W.; Van Duynhoven, J. P. M.; Reinhoudt, D. N.
J. Org. Chem. 1996, 61, 3476–3481. (b) Pelizzi, N.; Casnati,
A.; Ungaro, R. Chem. Commun. 1998, 2607–2608. (c)
Lazzarotto, M.; Sansone, F.; Baldini, L.; Casnati, A.; Cozzini,
P.; Ungaro, R. Eur. J. Org. Chem. 2001, 595–602.
1
8. (a) Lavielle, S.; Ling, N. C.; Guillemin, R. C. Carbohydr. Res.
1981, 89, 221–228. (b) Kov a´ cs, L.; O˝ sz, E.; Domokos, V.;
References and notes
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4609–4621.
1
. Lindhorst, T. K. Top. Curr. Chem. 2002, 218, 201–235.