Using click chemistry to access mono- and ditopic β-cyclodextrin hosts substituted by chiral amino acids

Article abstract of DOI:10.1016/j.carres.2010.11.024

A wide range of chiral mono- and ditopic cyclodextrin-based receptors have been synthesized by CuI-catalyzed azide-alkyne cycloaddition starting from mono-6-azido-β-cyclodextrin and chiral amino acids. Of interest, microwaves proved very efficient to acce

Full text of DOI:10.1016/j.carres.2010.11.024

Carbohydrate Research 346 (2011) 210–218
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Using click chemistry to access mono- and ditopic b-cyclodextrin hosts
substituted by chiral amino acids
Diem Ngan Tran a,b, Claire Blaszkiewicz a,b, Stéphane Menuel a,b, Alain Roucoux c, Karine Philippot d,
a,b
Frédéric Hapiot a,b, , Eric Monflier
⇑
a Univ Lille Nord de France, F-59000 Lille, France
b UArtois, UCCS, CNRS UMR 8181, F-62300 Lens, France
c Université Européenne de Bretagne, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, UMR 6226, Avenue du Général Leclerc, CS 50837, 35708 Rennes Cedex 7, France
d Université de Toulouse, UPS, INPT,CNRS LCC (Laboratoire de Chimie de Coordination), 205, Route de Narbonne, F-31077 Toulouse, France
a r t i c l e i n f o
a b s t r a c t
Article history:
A wide range of chiral mono- and ditopic cyclodextrin-based receptors have been synthesized by CuI-cat-
alyzed azide–alkyne cycloaddition starting from mono-6-azido-b-cyclodextrin and chiral amino acids. Of
interest, microwaves proved very efficient to access a wide range of ditopic b-cyclodextrin receptors with
quantitative yields.
Received 29 September 2010
Received in revised form 12 November 2010
Accepted 22 November 2010
Available online 27 November 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Cyclodextrins
Azides
Amino acids
Cycloaddition
Chirality
1. Introduction
is to give chemists a panel of easily-accessible tools to induce chi-
rality during supramolecular recognition processes, taking benefit
Knowledge on modified cyclodextrins (CDs) has reached a rela-
tively advanced, although always expanding, state. Their numerous
applications continue to attract much attention because they are
easy to handle and can supramolecularly interact with various
guests, such as organic, inorganic, or organometallic compounds.
Of special interest is the use of CDs modified by chiral substitu-
ents1 either to induce asymmetry on prochiral substrates during
the course of CD-promoted reactions2 or to discriminate organic
molecules by chromatography.1c,3 Thus, a general synthetic route
to large amounts of CDs substituted by chiral entities would be
useful for chemists dealing with asymmetry by supramolecular
means. Recently, click chemistry appeared as a very efficient tool
to synthesize b-CD derivatives bearing non-chiral substituents.4
In particular, using CuI-catalyzed azide–alkyne cycloaddition
(CuAAC), we developed syntheses of mono-, di-, and tritopic CDs,
which were easily obtained in good yields.5 To take the study a
step further, we extend our investigations to the synthesis of
mono- and ditopic CD-receptors substituted by chiral groups. To
our knowledge, only one publication refers to click synthesis of
CD conjugates substituted by a chiral entity.6 The aim of this study
from a chiral pocket generated by amino acid grafted CDs or CDs
linked together by chiral amino acid tethers. The synthesis and
characterization of these compounds are fully detailed below.
2. Results and discussion
2.1. Precursor’s synthesis
The synthesis of mono-6-azido b-CD (1) (Scheme 1) followed a
standard literature procedure.7 Partial methylation of 1 was carried
out as previously detailed to give RAME-b-CD-N3 (2) (Scheme 1).5b
Commercially available N-Boc-amino acids have been used as chi-
ral precursors.
L
-Alanine (a),
L-valine (b), L-isoleucine (c), L-leucine
(d), -proline (e), and
L
L
-phenylalanine (f) have been considered as
chiral entities in this study. Mono- (4a–f) and dialkynyl (5a–f) ami-
no acid derivatives have been synthesized as described on Scheme
2. Reaction of N-Boc-protected amino acids and propargylamine
with dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole
(HOBt) in refluxing dichloromethane led, after 2 h of vigorous
stirring, to yellow oils that were purified by column chromatogra-
phy using a dichloromethane–diethylether gradient. Compounds
3a–f were isolated as yellowish powders in moderate to very good
yields (90% to quantitative). Deprotection of the Boc protecting
⇑
Corresponding author. Tel.: +33 (0)321791773; fax: +33 (0)321791755.
E-mail address: hapiot@univ-artois.fr (F. Hapiot).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.11.024

D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
211
N3
OR
N3
5'
HO
HO
R
7
6'
6
H
1: R = H
O
O
2'
N
1
1'
5
O
R'HN
*
O
β
+
2
4
4'
RO
2: R = H or CH3
SD: 1.8
O
3
6
3'
OR
OR
RO
OH
amino acid derived
6
7
alkyne 4a-f
1
Scheme 1. Mono-6-azido b-CD (1) and randomly methylated mono-6-azido b-CD
(2) (SD: substitution degree).
CuSO4·xH2O
DMSO
r.t.
Na-ascorbate
group with trifluoacetic acid (TFA) yielded the alkynyl precursors
4a–f as yellow oils quantitatively. Subsequent reaction with propi-
olic acid proceeded for 2 h 30 min in dichloromethane at reflux in
the presence of DCC. Dialkynyl precursors 5a, 5b, and 5d were iso-
lated after extraction in water. On the contrary, purification of
compounds 5c, 5e, and 5f required elution on a silica column. It
should be noted that although 5d and 5f were isolated in moderate
yields (46% and 53%, respectively), no greater yield than 37% was
achieved for 5e suggesting that the cyclic moiety of proline affects
the reactivity of nitrogen toward the activated ester.
N
O
N
R'HN
*
N
H
N
R
OH
OH
7
7
β
HO
6a-f
6
Scheme 3. General scheme for the synthesis of monotopic amino acid-grafted b-
CD.
2.2. Synthesis of chiral monotopic b-CD receptors
2.3. Synthesis of chiral monotopic randomly methylated b-CD
receptors
To access chiral monotopic b-CD receptors, we pursued the
route previously used to synthesize non-chiral derivatives. Thus,
alkynyl precursors 4a–f were subjected to CuAAC with 1 and 1.3
equiv CuSO4ꢀxH2O (with respect to the CD) in DMSO at rt
(Scheme 3). DMSO has been chosen as solvent as its dissociating
character preserved Cu(II) to associate with the CD secondary face5
and thus improved their activity toward alkynyl derivatives. An ex-
cess alkynyl reactant (1.3 equiv with respect to the CD) was also
used to convert all the b-CD-N3 and avoid purification problems.
After addition of sodium ascorbate, the blue-green solution chan-
ged to a deep yellow color characteristic of cuprous acetylide in
the mixture. During the course of the reaction, the initial yellow
solution gradually turned to green. After 18 h reaction time, CDs
were precipitated by addition of acetone and easily separated from
DMSO and excess alkynes by filtration. Subsequent dissolution of
the CDs in diluted ammoniac gave a blue-violet solution indicative
of Cu-ammonia complexes. Purification of the crude product by
flash chromatography resulted in chiral monotopic b-CD receptors
6a–f as pale yellow powders, quantitatively. All new compounds
gave 1H, 13C NMR, and mass spectroscopic data consistent with
their structures. It should be pointed out that reactions of 1 with
alkynes derivatives are known to proceed exclusively at the C(4)
position.8
Facing the poor solubility of the hydroxylated b-CD derivatives
6a–f in water, the versatility of the above protocol was next exam-
ined with 2, leading to a series of randomly methylated b-CD
receptors (Scheme 4). The reaction proceeded cleanly over a period
of 18 h at rt. Removal of copper salts was achieved by addition of
an ammonia solution and subsequent filtration on a short silica
column using water as a mobile phase. Compounds 7a–f were ob-
tained quantitatively as pale yellow powders after evaporation of
the solvent. Note that long reaction times and stirring overnight
were required to allow for almost complete conversion of 2 and
maintain quantitative yield. Unambiguous determination of the
structure of 7a–f by 1H NMR was rendered difficult by peak broad-
ening in the 2.5–5.5 ppm region (CD protons) due to partial b-CD
methylation. Nevertheless, mass spectrometry confirmed the
modification to proceed as expected with the triazole cycle formed
between the amino acid moiety and the CD.
N3
R"O
R
*
7
H
N
R'HN
β
+
O
OR"
R"O
amino acid derived
4a-f
7
6
alkyne
R
2: R" = H or CH3 ; SD: 1.8
R
*
H
N
DCC/HOBt
H2N
+
OH
BocN
R'
*
BocN
R'
CH2Cl2
r.t. to reflux
CuSO4·xH2O
Na-ascorbate
MeOH
r.t.
O
O
3a-f
O
N
TFA
N
R'HN
*
N
H
N
R
OR"
OR"
R
*
O
R
*
7
7
H
N
H
COOH
N
HN
R'
β
N
DCC/HOBt
CH2Cl2
r.t. to efluxr
O
R"O
O
R'
7a-f
6
5a-f
4a-f
Scheme 4. General scheme for the synthesis of monotopic amino acid-grafted
randomly methylated b-CD.
Scheme 2. Synthesis of alkynyl-aminoacid precursors.

212
D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
2.4. Synthesis of chiral ditopic b-CD receptors
O
R
*
N3
OR
OR
H
N
7
+
N
The CuAAC has been extended to the synthesis of a series of
chiral ditopic b-CD receptors. Thus, 1,3-dipolar cycloaddition be-
tween a slight excess of 1 and 5a–f yields compounds 8a–f as pale
yellow powders after workup. Under standard CuAAC experimen-
tal conditions, 8a–f were obtained in poor yields (in the range of
10–34%). The yields strongly depend upon the bulkiness of the
amino-acid moiety. More constrained structures such as isoleucine
or proline derivatives gave moderate yields (10% and 15%, respec-
tively) when less hindered amino-acid derivatives gave good yields
(34% yield for the alanine derivative 8a). This observation corrobo-
rates the poor yield obtained for the proline precursor 5e (see
above). Conversely, under microwave irradiation, 8a–f were
obtained in quantitative yields whatever the amino-acid structure.
Reaction times are reduced from one night to 2 h, highlighting the
interest of microwaves in this [3+2] cycloaddition (Scheme 5).
Thus, joint use of CuAAC and microwaves appear the best method
ever described for the synthesis of a wide range of chiral ditopic
b-CD receptors. These results are in line with previous results ob-
tained by Cravotto and co-workers on the synthesis of bis-CDs
derivatives using microwaves.9
β
O
R'
RO
6
7
amino acid derived
dialkynes 5a-f
2
CuSO4·xH2O
Na-ascorbate
MeOH
MW, 60 °C, 2 h
O
R
N
N
H
N
N
N
N
*
N
N
O
R'
RO
RO
OR
OR
7
7
7
β
β
OR
RO
6
6
7
9a-f
Scheme 6. General scheme for the synthesis of ditopic randomly methylated b-CD
dimers containing an amino acid linker under microwave.
2.5. Synthesis of chiral ditopic randomly methylated b-CD
receptors
promoted CuAAC proved very efficient to access chiral ditopic
CD-based receptors in quantitative yields. Further investigations
to take advantage of the polyvalency of the synthesized b-CD
receptors in supramolecular chemistry and aqueous catalysis are
currently on-going.
The above results have been confirmed on chiral ditopic ran-
domly methylated b-CD receptors (Scheme 6). Facing the poor
yields obtained using classical CuAAC conditions, the syntheses
have been performed under microwaves. Here again, as for hydrox-
ylated ditopic b-CD receptors, no steric dependence of the yield
was noticed. Compounds 9a–f were obtained in quantitative yields
as pale yellow powders after workup. The structure of 9a–f was
fully confirmed by NMR and mass spectrometry.
4. Experimental section
4.1. General
3. Conclusions
All chemicals were purchased from Acros and Aldrich Chemicals
in their highest purity. All solvents were used as supplied without
further purification. Distilled water was used in all experiments.
Where solvent mixtures are used, the portions are given by vol-
ume. Analytical thin-layer chromatography (TLC) was performed
on precoated plates (Merck aluminium sheets, Silica Gel 60 F254,
0.2 mm). Compounds were identified using UV fluorescence and/
or staining with a solution of ninhydrin. NMR spectra were
recorded on a Bruker DRX300 spectrometer operating at 300 MHz
for 1H nuclei and 75 MHz for 13C nuclei. CDCl3 (99.50% isotopic
purity), DMSO-d6 (99.80% isotopic purity), and D2O (99.92% isoto-
pic purity) were purchased from Euristop. Signals were recorded
in terms of chemical shifts and are expressed in parts per million
(d), multiplicity, coupling constants (in Hz, rounded to one decimal
place), integration, and assignments in that order. The correct
assignments of the chemical shifts were confirmed when necessary
by two-dimensional correlation measurements attained by 1H–1H
COSY, 1H–13C HSQC, or 1H–13C HMBC experiments. Protons of the
substituted glucopyranose unit of b-CD are noted as H0. Mass
spectra were recorded on a MALDI–TOF/TOF Bruker Daltonics
Ultraflex II in positive reflectron mode with 2,5-DHB as matrix.
To conclude, the synthesis of chiral ditopic b-CD receptors ap-
peared more challenging than anticipated. However, microwave-
O
R
*
N3
OH
OH
H
N
7
7
N
+
β
O
R'
HO
6
aminoacid derived
dialkynes 5a-f
1
CuSO4·xH2O
Na-ascorbate
DMF
MW, 60 °C, 2 h
O
R
N
H
N
N
N
N
N
*
N
N
O
R'
HO
HO
OH
OH
7
7
7
Microwave-promoted reactions were carried out using
a
CEM-MARS multimodal microwave reactor (CEM Corporation),
the temperature being monitored with a fiber-optic thermometer.
β
β
OH
HO
a DT
were determined using an Atago polarimeter AP-300. Optical
ꢁ
6
6
½
7
rotation of the hydroxylated derivatives 6a–f and 8a–f could
not be determined due to their poor solubility in water and
organic solvents. Elemental analysis has been carried out using a
ThermoQuest EA 110 CHNS.
8a-f
Scheme 5. General scheme for the synthesis of ditopic b-CD dimers containing an
amino acid linker.

D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
213
4.2. General procedure for the synthesis of N-Boc-protected
4.2.5. Boc-L-proline-N-propargylamide (3e)
alkynes 3a–f
White powder. Yield 2.52 g, quantitative; Rf = 0.4 (hexane–
EtOAc, 1:1); ½a 2D2
ꢃ71.9 (c 1.4, CHCl3); dH (CDCl3) 7.26 and 6.27
ꢁ
To a solution of N-Boc-amino acid (10 mmol) and 1-hydroxy-
benzotriazole (HOBt) (10 mmol) in CH2Cl2 (100 mL) was added
propargylamine (12 mmol). After 30 min. stirring at rt under N2,
dicyclohexylcarbodiimide (DCC) (13 mmol) was added and the
reaction mixture was refluxed under vigorous stirring for 2 h. After
cooling at rt for 1 h, a white powder precipitated and was filtered
off on a glass filter. The filtrate was evaporated under vacuum. The
resulting viscous yellow oil was extracted with diethyl ether
(2 ꢂ 300 mL). The crude product was purified by column chroma-
tography using a dichloromethane–diethyl ether mixture (5:5 for
3b, 8:2 for the others) as the eluant. The product was isolated after
evaporation of the solvents under vacuum.
(s, 0.5H and s, 0.5H, NH), 4.24 (m, 1H, CH), 3.98 (m, 2H, CH2C„),
3.43 (m, 2H, CH2N), 2.21 (m, 1H, CHHCHN), 2.19 (s, 1H, HC„),
1.85 (br s, 3H, CHHCHN, CH2CH2CHN), 1.44 (m, 9H, (CH3)3); dC
(CDCl3) 172.42 and 171.85 (CONHCH2), 156.12 and 154.73 (CO
Boc), 80.84 (C(CH3)3), 79.59 (HC„), 71.85 and 71.42 (C„CH),
61.25 and 59.89 (CHN), 47.22 (CH2N), 31.05 and 27.94 (CH2CHN),
29.14 (CH2C„), 28.46 (C(CH3)3), 23.93 and 24.68 (CH2CH2N). Anal.
Calcd for C13H20N2O3ꢀH2O: C, 57.76; H, 8.20; N, 10.35. Found: C,
58.06; H, 8.33; N, 10.32.
4.2.6. Boc-L-phenylalanine-N-propargylamide (3f)
White powder. Yield 3.02 g, quantitative; Rf = 0.48 (hexane–
EtOAc, 1:1); ½a 2D2
ꢁ
+1.1 (c 1.4, CHCl3); dH (CDCl3) 7.29–7.20 (m, 5H,
4.2.1. Boc-L-alanine-N-propargylamide (3a)
Ar-H), 6.25 (br s, 1H, NH), 5.08 (br s, 1H, NH), 4.36 (m, 1H,
HNCHCO), 3.99 (m, 2H, CH2C„), 3.07 (m, 2H, CH2-Ar), 2.20 (s,
1H, HC„), 1.42 (m, 9H, (CH3)3); dC (CDCl3) 171.70 (CONHCH2),
155.70 (CO Boc), 136.72 (Cquat Ar), 129.42, 128.64 and 126.99
(Ar), 80.12 (C(CH3)3), 79.28 (CH„), 71.65 (C„CH), 55.69 (CHN),
38.79 (CH2CHN), 30.31 (CH2C„), 29.00 (CH3). Anal. Calcd for
Pale yellow powder. Yield 2.03 g, 90%; Rf = 0.6 (hexane–EtOAc,
1:1); ½a 2D2
ꢃ24.7 (c 1.2, CHCl3); dH (CDCl3) 6.78 (s, 1H, NHCH2),
ꢁ
5.14 (s, 1H, NHCH), 4.21 (m, 1H, CH), 4.03 (d, J = 2.5 Hz, 2H, CH2),
2.20 (t, J = 2.5 Hz, 1H, HC„), 1.43 (s, 9H, (CH3)3C), 1.35 (d,
J = 7.1 Hz, 3H, CH3); dC (CDCl3) 172.61 (CONHCH2), 155.71 (CO
Boc), 80.34 (C(CH3)3), 79.46 (HC„), 71.65 (C„CH), 49.98 (CH),
29.19 (CH2), 28.42 (C(CH3)3), 18.41 (CH3). Anal. Calcd for
C
17H22N2O3ꢀCH2Cl2: C, 55.82; H, 6.76; N, 7.23. Found: C, 55.90; H,
6.69; N, 7.08.
C
11H18N2O3ꢀCH2Cl2: C, 46.31; H, 6.47; N, 8.99. Found: C, 46.62; H,
7.12; N, 9.14.
4.3. General procedure for the synthesis of alkynyl precursors
4a–f
4.2.2. Boc-L-valine-N-propargylamide (3b)
Compounds 3a–f (6 mmol) were dissolved in a TFA–CH2Cl2
mixture (1:2, 30 mL) and stirred at rt for 15 min. After evaporation
of the solvent and excess TFA, the obtained brown oil was dis-
solved in water (100 mL). Amberlite IRA 900 resin (conditioned
in a basic solution) was then added to adjust the pH to 8. The resin
was filtered through a glass filter and washed with 50 mL water.
Evaporation of the filtrate gave viscous yellow oil.
White powder. Yield 2.54 g, quantitative; Rf = 0.5 (hexane–
EtOAc, 1:1); ½a 2D2
ꢃ11.4 (c 1.5, CHCl3); dH (CDCl3) 6.43 (s, 1H,
ꢁ
NHCH2), 5.08 (d, J = 7.0 Hz, 1H, NHCH), 4.04 (m, 2H, CH2), 3.92
(dd, J = 8.6 Hz, J = 7.0 Hz, 1H, CH), 2.21 (t, J = 2.5 Hz, 1H, HC„),
2.10 (m, 1H, CH(CH3)2), 1.44 (s, 9H, (CH3)3C), 0.96 (d, J = 6.8 Hz,
3H, CH3), 0.92 (d, J = 6.8 Hz, 3H, CH3). dC (CDCl3) 171.93
(CONHCH2), 156.12 (CO Boc), 79.88 (C(CH3)3), 79.54 (HC„),
71.41 (C„CH), 59.78 (CH), 31.34 (CH(CH3)2)), 28.92 (CH2),
28.43 (C(CH3)3), 19.25 (CH3), 18.28 (CH3). Anal. Calcd for
4.3.1. L-Alanine-N-propargylamide (4a)
Yield 726 mg, 96%; ½a D22
ꢁ
+5.6 (c 1.1, MeOH); dH (CDCl3) 7.58 (s, 1H,
C
13H22N2O3ꢀ2H2O: C, 53.78; H, 9.02; N, 9.64. Found: C, 54.29; H,
9.14; N, 9.76.
NH), 4.03 (m, 2H, CH2), 3.47 (m, 1H, CH), 2.21 (t, J = 2.5 Hz, 1H, HC„),
1.73 (br s, 2H, NH2), 1.32 (d, J = 7.0 Hz, 3H, CH3); dC (75.5 MHz, CDCl3)
175.54 (CO), 79.95 (HC„), 71.60 (C„CH), 50.81 (CH), 28.87 (CH2),
21.71 (CH3). Anal. Calcd for C6H10N2OꢀH2O: C, 50.00; H, 8.38; N,
19.42. Found: C, 50.11; H, 8.65; N, 19.83.
4.2.3. Boc-L-isoleucine-N-propargylamide (3c)
White powder. Yield 2.65 g, quantitative; Rf = 0.7 (hexane–
EtOAc, 1:1); ½a 2D2
ꢃ87.2 (c 1.3, CHCl3); dH (CDCl3) 6,45 (s, 1H,
ꢁ
NHCH2), 5.09 (d, J = 7.0 Hz, 1H, NHCH), 4.06 (m, 2H, CH2), 3.98
(m, 1H, CHNH), 2.23 (t, J = 2.5 Hz, 1H, HC„), 1.90 (m, 1H,
CH3CH2CHCH3), 1.50 (br s, 10H, CH3CHH, (CH3)3C), 1.13 (m, 1H,
CH3CHH), 0.93 (m, 6H, CH3CH2, CH3CH); dC (CDCl3) 171.83
(CONHCH2), 156.04 (CO Boc), 80.06 (C(CH3)3), 79.44 (HC„),
71.59 (C„CH), 59.10 (CH), 37.40 (CH3CH2CHCH3), 29.05 (CH2),
28.44 (C(CH3)3), 24.89 (CH3CH2), 15.57 (CH3CH), 11.37 (CH3CH2).
Anal. Calcd for C14H24N2O3ꢀCH2Cl2: C, 47.60; H, 7.41; N, 7.93.
Found: C, 47.02; H, 7.67; N, 7.51.
4.3.2. L-Valine-N-propargylamide (4b)
Yield 906 mg, 98%; ½a D22
ꢁ
+11.9 (c 1.3, MeOH); dH (CDCl3) 7.60 (br
s, 1H, NH), 4.02 (dd, J = 5.1 Hz, J = 2.5 Hz, 2H, CH2), 3.24 (d,
J = 3.5 Hz, 1H, CHNH2), 2.27 (m, 1H, CH(CH3)2), 2.19 (t, J = 2.5 Hz,
1H, HC„), 1.74 (br s, 2H, NH2), 0.96 (d, J = 6.9 Hz, 3H, CH3), 0.80
(d, J = 6.9 Hz, 3H, CH3); dC (CDCl3) 174.32 (CO) 80.09 (HC„),
71.13 (C„CH), 59.96 (CHNH2), 30.93 (CH(CH3)2), 28.58 (CH2),
19.61 (CH3), 16.03 (CH3). Anal. Calcd for C8H14N2OꢀH2O: C, 55.83;
H, 9.30; N, 16.28. Found: C, 56.45; H, 10.01; N, 16.34.
4.2.4. Boc-L-leucine-N-propargylamide (3d)
White powder. Yield 2.68 g, quantitative; Rf = 0.7 (hexane–
4.3.3. L-Isoleucine-N-propargylamide (4c)
EtOAc, 1:1); ½a 2D2
ꢃ29.1 (c 1.4, CHCl3); dH (CDCl3) 6.40 (s, 1H,
ꢁ
Yield 989 mg, 98%; ½a D22
ꢁ
+13.1 (c 1.1, MeOH); dH (CDCl3) 7.67 (s,
NHCH2), 4.81 (d, J = 6.9 Hz, 1H, NHCH), 4.09 (m, 1H, CHNH), 4.05
(m, 2H, CH2), 2.22 (t, J = 2.5 Hz, 1H, HC„), 1.68 (m, 2H, CH2CHNH),
1.44 (br s, 10H, CH(CH3)2, (CH3)3C), 0.94 (2 d, J = 7.0 Hz, 6H,
2 ꢂ CH3); dC (CDCl3) 172.66 (CONHCH2), 155.89 (CO Boc), 80.05
(C(CH3)3), 79.41 (HC„), 71.47 (C„CH), 52.79 (CHNH), 41.30
(CH2CHNH), 29.03 (CH2NH), 28.33 (C(CH3)3), 24.67 (CH(CH3)2),
22.97 (CH3), 21.92 (CH3). Anal. Calcd for C14H24N2O3ꢀH2OꢀCH2Cl2:
C, 48.53; H, 7.59; N, 7.54. Found: C, 48.81; H, 7.45; N, 7.76.
1H, NH), 4.05 (dd, J = 2.5 Hz, J = 5.3 Hz, 2H, CH2), 3.38 (d, J = 4.1 Hz,
1H, CHNH2), 2.27 (s, 2H, NH2), 2.22 (t, J = 2.5 Hz, 1H, HC„), 2.02 (m,
1H, CHCHNH2), 1.38 (m, 1H, CHHCH3), 1.12 (m, 1H, CHHCH3), 0.97
(d, J = 7.1 Hz, 3H, CH3CH2), 0.89 (t, J = 7.2 Hz, 3H, CH3CH); dC
(CDCl3) 172.83 (CO), 78.85 (HC„), 70.37 (C„CH), 58.71 (CHNH2),
36.93 (CHCHNH2), 27.84 (CH2C„), 22.81 (CH2CH3), 15.16 (CH3CH),
11.00 (CH3CH2). Anal. Calcd for C9H16N2Oꢀ2H2O: C, 52.92; H, 9.86;
N, 13.71. Found: C, 52.89; H, 10.04; N, 13.39.

214
D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
4.3.4.
L
-Leucine-N-propargylamide (4d)
4.4.3. a-N-Ethylnyl-L-isoleucine-N-propargylamide (5c)
Yield 938 mg, 93%; ½a D22
ꢁ
+8.6 (c 1.0, MeOH); dH (CDCl3) 7.62 (s, 1H,
The product was purified by column chromatography with a
gradient concentration of hexane–EtOAc (from 9:1 to 1:1) as elu-
ent. After evaporation of the solvents, 5c was isolated as a yellow
NH), 4.04 (m, 2H, CH2), 3.42 (d, J = 4.1 Hz, 1H, CHNH2), 2.21 (s, 2H,
NH2), 2.12 (t, J = 2.5 Hz, 1H, HC„), 1.93 (m, 1H, CHHCHNH2),
1.85 (m, 1H, CHHCHNH2), 1.02 (m, 1H, CH(CH3)2), 0.89 (m, 6H,
2 ꢂ CH3); dC (CDCl3) 173.28 (CO), 79.12 (HC„), 70.7 (HC„), 57.02
(CHNH2), 38.24 (CH2CHNH2), 28.03 (CH2C„), 24.87 (CH(CH3)2),
16.35 (CH3), 16.18 (CH3). Anal. Calcd for C9H16N2OꢀH2O: C, 58.04;
H, 15.03; N, 10.86. Found: C, 58.35; H, 14.96; N, 10.69.
powder. Yield 304 mg, 46%; ½a D22
ꢃ13.7 (c 1.0, MeOH); dH (CDCl3)
ꢁ
6.68 (d, J = 8.2 Hz, 1H, NHCH), 6.40 (s, 1H, NHCH2), 4.34 (m, 1H,
CHNH), 4.05 (m, 2H, CH2C„), 2.86 (s, 1H, HC„C(CO)), 2.24 (t,
J = 2.5 Hz, 1H, HC„CCH2), 1.87 (m, 1H, CHCHNH), 1.61 (m, 1H,
CH3CHH), 1.18 (m, 1H, CH3CHH), 0.94 (m, 6H, CH3CHH, CH3CH2);
dC (CDCl3) 170.36 ((CO)C„), 152.24 (CONHCH2), 79.08 (HC„CCH2),
76.09 (HC„C(CO)), 74.60 (HC„C(CO)), 71.89 (HC„CCH2), 57.97
(CHNH), 37.76 (CHCHNH), 29.29 (CH2), 25.08 (CH2CH3), 15.39
(CH3CH), 11.29 (CH3CH2).
4.3.5. L-Proline-N-propargylamide (4e)
Yield 894 mg, 98%; ½a D22
ꢃ60.6 (c 1.0, MeOH); dH (CDCl3) 8.35 (t,
ꢁ
J = 5.0 Hz, 1H, NHCO), 5.38 (br s, 1H, NHCH), 4.14 (q, J = 8.9 Hz, J
5.8 Hz, 1H, CH), 4.02 (q, J = 5.4 Hz, J = 2.5 Hz, 2H, CH2C„), 3.16
(m, 2H, CH2CH2NH), 2.31 (m, 1H, CHHCHNH), 2.24 (t, J = 2.5 Hz,
1H, HC„), 1.99 (m, 1H, CHHCHNH), 1.84 (m, 2H, CH2CH2NH); dC
(CDCl3) 169.94 (CO), 79.12 (HC„), 71.75 (C„CH), 59.91 (CHNH),
46.94 (CH2CH2NH), 30.58 (CH2CHNH), 29.53 (CH2C„), 25.07
(CH2CH2NH). Anal. Calcd for C8H12N2OꢀH2O: C, 56.48; H, 8.23; N,
16.47. Found: C, 57.18; H, 8.43; N, 17.01.
4.4.4. a-N-Ethylnyl-L-leucine-N-propargylamide (5d)
The product was isolated as a white powder after extraction with
water (6 ꢂ 50 mL). Yield 284 mg, 43%; ½a D22
ꢃ23.3 (c 1.1, MeOH); dH
ꢁ
(CDCl3) 6.46 (d, J = 8.6 Hz, 1H, NHCH), 6.33 (s, 1H, NHCH2), 4.50 (m,
1H, CHNH), 4.05 (m, 2H, CH2), 2.88 (s, 1H, HC„C(CO)), 2.27 (t,
J = 2.4 Hz, 1H, HC„CCH2), 1.86 (m, 1H, CHHCHNH), 1.73 (m, 1H,
CHHCHNH), 1.29 (m, 1H, CH(CH3)2), 0.96 (m, 6H, 2 ꢂ CH3); dC (CDCl3)
171.20 ((CO)C„), 152.22 (CONHCH2), 79.03 (HC„CCH2), 76.52
(HC„C(CO)), 74.60 (HC„C(CO)), 71.78 (HC„CCH2), 51.86 (CHNH),
41.14 (CH2CHNH), 29.25 (CH2C„), 24.68 (CH(CH3)2), 22.85 (CH3CH),
22.09 (CH3CH).
4.3.6. L-Phenylalanine-N-propargylamide (4f)
Yield 982 mg, 81%; ½a D22
ꢁ
+8.2 (c 1.1, MeOH); dH (CDCl3) 7.58 (br
s, 1H, NHCO), 7.35–7.21 (m, 5H, Ar-H), 4.06 (s, 2H, CH2C„), 3.62
(m, 1H, CH), 3.29 (dd, J = 14.0 Hz, J = 4.0 Hz, 1H, CHHCHNH2), 2.70
(dd, J = 14 Hz, J = 9.0 Hz, 1H, CHHCHNH2), 2.23 (t, J = 3.0 Hz, 1H,
HC„), 1.30 (br s, 2H, NH2); dC (CDCl3) 174.14 (d, CO), 137.80 (Cquat
Ar), 129.30, 128.71 and 126.84 (Ar), 77.26 (HC„), 71.44 (C„CH),
56.20 (CHNH2), 40.83 (CH2CHNH2), 28.71 (CH2C„). Anal. calcd
for C12H14N2Oꢀ2H2O: C, 60.49; H, 7.61; N, 11.75. Found: C, 60.52;
H, 7.66; N, 11.54.
4.4.5. a-N-Ethylnyl-L-proline-N-propargylamide (5e)
The product was purified by column chromatography with a gra-
dient concentration of hexane–EtOAc–MeOH (7:2.5:0.5) as the elu-
ent. After evaporation of the solvents, 5e was isolated as a pale
yellow powder. Yield 227 mg, 37%; ½a D22
ꢃ74.8 (c 1.0, MeOH); dH
ꢁ
(CDCl3) 7.19 and 6.49 (s, 0.8H and s, 0.2H, NH), 4.55 (m, 1H, CHN),
4.00 (m, 2H, CH2C„), 3.73 (m, 2H, CH2N), 3.17 (s, 1H, HC„C(CO)),
2.49 (m, 1H, CHHCHN), 2.21 (t, J = 2.5 Hz, 1H, HC„CCH2), 2.01 (m,
3H, CHHCHN, CH2C„); dC (CDCl3) 170.98 and 169.80 ((CO)C„CH),
153.32 and 152.81 ((CO)CH), 79.45 (HC„C(CO)), 79.14 (HC„CCH2),
76.16 (HC„C(CO)), 71.61 (HC„CCH2), 62.91 and 59.49 (CHNH),
49.18 and 46.62 (CH2N), 31.09 and 29.80 (CH2CHN), 27.57 (CH2C„),
24.42 and 23.20 (CH2CH2N).
4.4. General procedure for the synthesis of di-alkynyl
precursors 5a–f
To a solution of propiolic acid (1.2 equiv) in CH2Cl2 (100 mL)
was added DCC (1.6 equiv). The solution was stirred for 30 min
at rt under N2. Compounds 4a–f (3 mmol) in CH2Cl2 (10 mL) was
then added dropwise over a period of 30 min. The resulting mix-
ture was heated at reflux with vigorous stirring for 1 h. After cool-
ing to rt, a white powder precipitated and was filtered off. The
filtrate was evaporated and purified by column chromatography
or extraction with water.
4.4.6. a-N-Ethylnyl-L-phenylalanine-N-propargylamide (5f)
The product was purified by column chromatography with a
gradient concentration of CH2Cl2–Et2O–MeOH (8:1.9:0.1) as the
eluent. After evaporation of the solvents, 5f was isolated as a pale
4.4.1.
a
-N-Ethylnyl-L-alanine-N-propargylamide (5a)
yellow powder. Yield 454 mg, 60%; ½a D22
ꢃ10.0 (c 1.0, MeOH); dH
ꢁ
The product was isolated as a white powder after extraction
(CDCl3) 7.34–7.22 (m, 5H, Ar-H), 6.69 (d, J = 7.0 Hz, 1H, NHCH),
5.78 (s, 1H, NHCH2), 4.64 (dd, J = 14.0 Hz, J = 8.0 Hz, 1H, CHNH),
3.97 (d, J = 3.0 Hz, 2H, CH2C„), 3.17 (dd, J = 14.0 Hz, J = 6.0 Hz,
1H, CH2CHNH), 3.03 (dd, J = 8.0 Hz, J = 6.0 Hz, 1H, CH2CHNH),
2.86 (s, 1H, HC„C(CO)), 2.22 (s, 1H, HC„CCH2); dC (CDCl3)
169.99 (CO), 151.98 (CO), 136.17 (Cquat Ar), 128.76, 127.25,
125.55 (Ar), 78.82 (HC„CCH2), 76.71 (HC„C(CO)), 74.79 (HC„
C(CO)), 71.85 (HC„CCH2), 54.73 (CHNH), 38.41 (CH2NH), 29.40
(CH2-Ar).
with water (2 ꢂ 100 mL) and evaporation of the solvent. Yield
374 mg, 70%; ½a 2D2
ꢃ21.4 (c 1.0, MeOH); dH (DMSO-d6) 8.95 (d,
ꢁ
J = 7.7 Hz, 1H, NHCH), 8.39 (t, J = 5.5 Hz, 1H, NHCH2), 4.24 (m, 1H,
CH), 4.16 (s, 1H, HC„C(CO)), 3.84 (dd, J = 2.6 Hz, J = 5.3 Hz, 2H,
CH2), 3.11 (t, J = 2.4 Hz, 1H, HC„CCH2), 1.19 (d, J = 7.0 Hz, 3H,
CH3); dC (DMSO-d6) 171.28 ((CO)C„), 151.39 ((CO)CH), 81.04
(HC„CCH2), 78.15 (HC„C(CO)), 76.27 („C(CO)), 73.09 („CCH2),
48.40 (CH), 28.02 (CH2), 17.57 (CH3).
4.4.2.
a
-N-Ethylnyl-L-valine-N-propargylamide (5b)
4.5. General procedure for the synthesis of monotopic b-CD
The product was isolated as a white powder after extraction
receptors 6a–f
with water (3 ꢂ 100 mL). Yield 390 mg, 63%; ½a D22
ꢃ24.9 (c 1.0,
ꢁ
MeOH); dH (CDCl3) 6.68 (d, J = 8.2 Hz, 1H, NHCH), 6.38 (s, 1H,
NHCH2), 4.30 (dd, J = 8.7 Hz, J = 7.0 Hz, 1H, CHNH), 4.06 (m, 2H,
CH2), 2.86 (s, 1H, HC„C(CO)), 2.25 (t, J = 2.5 Hz, 1H, HC„CCH2),
2.10 (m, 1H, CH(CH3)2), 0.98 (d, J = 6.8 Hz, 6H, 2 CH3); dC (CDCl3)
170.09 ((CO)C„), 152.18 ((CO)CH), 78.88 (HC„CCH2), 76.77
(HC„C(CO)), 74.48 („C(CO)), 71.88 („CCH2), 58.67 (CHNH),
31.53 (CH(CH3)2), 29.21 (CH2), 19.11 (CH3), 18.31 (CH3).
To a solution of 4a–f (0.56 mmol) in DMSO (5 mL) was added 1
(0.43 mmol) and CuSO4ꢀ5H2O (0.56 mmol). Sodium ascorbate
(1.12 mmol) in H2O (2 mL) was added dropwise over 15 min. The
reaction mixture was vigorously stirred at rt for 18 h. Addition of
acetone (50 mL) induced precipitation of a white powder which
was recovered by filtration on a glass filter. The powder was
dissolved in aqueous ammonia (8 wt %) and purified by column

D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
215
chromatography with water as eluent. Evaporation of the solvent
gave a pale yellow powder.
169.75 (CO), 144.15 (Cquat triazole), 125.26 (CH triazole), 102.18
(C1), 81.29 (C4), 73.03–71.92 (C2, C3, C5), 60.27 (C6), 59.80 (CHNH2),
46.49 (CH2NH), 34.53 (CH2NH), 29.62 (CH2), 23.84 (CH2); m/z
1334.09 (calcd 1334.46 for [C50H81N5O35+Na]+), 1350.08 (calcd
1350.57 for [C50H81N5O35+K]+).
4.5.1. L-Alanine-N-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-
yl)methylamide] (6a)
Yield 553 mg, quantitative; dH (D2O) 7.84 (s, 1H, H triazole),
5.03–4.86 (m, 7H, H1, H0 ), 4.41 (m, 2H, CH2NH), 4.21 (s, 1H, CHNH2),
1
4.5.6. L-Phenylalanine-N-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-
4-yl)methylamide] (6f)
4.04 (m, 1H, H0), 3.94 (m, 1H, H0), 3.74 (m, 24H, H3, H5, H6), 3.54–3.48
(m, 14H, H2, H4, 2 ꢂ H0), 3.02 (m, 1H, H0), 2.81 (s, 1H, H0), 1.35 (m, 3H,
CH3); dC (D2O) 170.71 (CO), 143.77 (Cquat triazole), 125.34 (CH tria-
zole), 101.82 (C1), 81.04 (C4), 73.16–70.50 (C2, C3, C5), 63.52 and
Yield 585 mg, quantitative; dH (D2O) 7.14–7.04 (m, 6H, Ar-H, H
triazole), 5.08–4.52 (m, 7H, H1, H0 ), 4.46 (m, 3H, CHNH2, CH2NH),
1
4.09 (m, 1H, H0), 3.75 (m, 25H, H3, H5, H6, H60 ), 3.56 (m, 14H, H2,
H4, 2 ꢂ H0), 3.45 (m, 1H, H0), 3.14 (m, 1H, CH2-Ar), 2.92 (m, 2H,
CH2-Ar, H0); dC (D2O) 174.68 (CO), 144.15 (Cquat triazole), 134.64
(Cquat Ar), 129.22, 128.66 and 127.63 (Ar), 126.71 (CH triazole),
102.15 (C1), 81.11 (C4), 73.26–72.01 (C2, C3, C5), 60.54 (C6), 60.29
(CHNH2), 36.69 (CH2-Ar), 34.24 (CH2NH); m/z 1384.07 (calcd
1384.48 for [C54H83N5O35+Na]+), 1400.05 (calcd 1400.45 for
[C54H83N5O35+K]+).
0
60.97 (C6, C6 ), 49.01 (CHNH2), 34.60 (CH2NH), 16.43 (CH3); m/z
1308.23 (calcd 1308.45 for [C48H79N5O35+Na]+), 1324.22 (calcd
1324.56 for [C48H79N5O35+K]+).
4.5.2. L-Valine-N-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)
methylamide] (6b)
Yield 565 mg, quantitative; dH (D2O) 7.86 (s, 1H, H triazole),
5.50–4.84 (m, 7H, H1, H0 ), 4.42 (d, J = 9.0 Hz, 2H, CH2NH), 4.28
1
(dd, J = 14.0 Hz, J = 8.0 Hz, 1H, CHNH2), 4.20 (m, 1H, H0), 4.05 (m,
1H, H0), 3.89–3.68 (m, 26H, H3, H5, H6, 2 ꢂ H0), 3.56–3.39 (m,
12H, H2, H4), 3.07 (d, J = 12.0 Hz, 1H, H0), 2.76 (m, 1H, H0), 2.00
(m, 1H, CH(CH3)2), 0.85 (m, 3H, CH3), 0.83 (m, 3H, CH3); dC (D2O)
176.15 and 170.51 (CO), 144.06 (Cquat triazole), 126.71 (CH tria-
4.6. General procedure for the synthesis of randomly
methylated monotopic b-CD receptors 7a–f
To a solution of 4a–f (0.41 mmol) in MeOH (5 mL) was added 2
(0.37 mmol) and CuSO4ꢀ5H2O (0.41 mmol). Once the solution was
clear, sodium ascorbate (0.82 mmol) in H2O (2 mL) was added
dropwise over 15 min. The reaction mixture was vigorously stirred
at rt for 18 h. MeOH was concentrated. The powder was dissolved
in aqueous ammonia (8 wt %) and purified by column chromatog-
raphy with water as eluent. Evaporation of the solvent gave a pale
yellow powder.
0
0
zole), 102.88 (C1), 100.71 (C1 ), 82.09 (C4), 79.94 (C4 ), 75.44–
71.59 (C2, C3, C5), 70.68 (C6), 60.15 (CHNH2), 37.78 (CH2NH),
35.83 (CH(CH3)2), 30.99 (CH3), 29.35 (CH3); m/z 1336.39 (calcd
1336.48 for [C50H83N5O35+Na]+), 1352.40 (calcd 1352.59 for
[C50H83N5O35+K]+).
4.5.3. L-Isoleucine-N-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)
methylamide] (6c)
Yield 571 mg, quantitative; dH (D2O) 7.85 (s, 1H, H triazole),
5.07–4.89 (m, 7H, H1, H0 ), 4.52 (m, 1H, CHNH2), 4.42 (m, 2H,
CH2NH), 4.21 (m, 2H, 2 ꢂ1H0), 3.76 (m, 24H, H3, H5, H6), 3.55–3.39
(m, 14H, H2, H4, 2 ꢂ H0), 3.08 (m, 1H, H0), 2.77 (m, 1H, H0), 1.79
(m, 1H, CHCHNH2), 1.36 (m, 1H, CH3CHH), 1.07 (m, 1H, CH3CHH),
0.81 (m, 6H, CH3CH, CH3CH2); dC (D2O) 170.57 (CO), 144.58 (Cquat
triazole), 125.26 (CH triazole), 101.86 (C1), 81.10 (C4), 73.03–
71.96 (C2, C3, C5), 59.17 (C6), 57.92 (CHNH2), 36.71 (CHCHNH2),
34.41 (CH2NH), 24.51 (CH2CH3), 14.26 (CH3), 17.56 (CH3); m/z
1350.41 (calcd 1350.49 for [C51H85N5O35+Na]+), 1366.43 (calcd
1366.60 for [C51H85N5O35+K]+).
4.6.1. L-Alanine-N-[(1-randomly methylated-b-cyclodextrinyl-
1H-1,2,3-triazol-4-yl)methylamide] (7a)
Yield 542 mg, quantitative; ½a D20
ꢁ
+87.3 (c 0.5, H2O); dH (D2O)
7.92 (s, 1H, H triazole), 5.15 (m, 7H, H1, H01), 4.43 (s, 1H, H0), 4.21
(s, 2H, CHNH2, H0), 4.11 (s, 2H, CH2NH), 3.81 (m, 10H), 3.61–3.45
(55H), 3.27 (m, 15H), 3.15 (s, 1H, H0), 3.06 (s, 1H, H0), 1.45 (d, 3H,
CH3); dC (D2O) 178.79 and 170.76 (CO), 143.99 (Cquat triazole),
125.63 (CH triazole), 100.53–98.78 (C1), 82.32–81.17 (C4),
73.33–69.91 (C2, C3, C5), 64.03–62.19 (C6, C06), 59.61–59.04
(OCH3), 58.32 (CHNH2), 34.33 (CH2NH), 16.49 (CH3); m/z (%)
1462.18 (1.5) (calcd 1462.27 for [C59H101N5O35+Na]+), 1476.20
(14.7) (calcd 1476.28 for [C60H103N5O35+Na]+), 1490.22 (65.6)
(calcd 1490.29 for [C61H105N5O35+Na]+), 1504.24 (14.4) (calcd
1504.30 for [C62H107N5O35+Na]+), 1518.24 (2.0) (calcd 1518.31
for [C63H109N5O35+Na]+), 1532.22 (1.9) (calcd 1532.32 for
[C64H111N5O35+Na]+).
4.5.4. L-Leucine-N-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)
methylamide] (6d)
Yield 571 mg, quantitative; dH (D2O) 7.78 (s, 1H, H triazole),
5.06–4.87 (m, 7H, H1, H0 ), 4.53–4.46 (m, 3H, CHNH2, CH2NH),
1
4.36 (s, 1H, H0), 4.21 (s, 1H, H0), 3.83–3.69 (m, 25H, H3, H5, H6,
0
H6 ), 3.54–3.44 (m, 13H, H2, H4, H0), 3.36 (d, J = 7.0 Hz, 1H, H0),
3.05 (d, J = 12.0 Hz, 1H, H0), 1.58–1.45 (m, 3H, CH2CHNH2,
CH(CH3)2), 0.81 (m, 6H, 2 ꢂ CH3); dC (D2O) 176.27–171.99 (CO),
4.6.2. L-Valine-N-[(1-randomly methylated-b-cyclodextrinyl-
1H-1,2,3-triazol-4-yl)methylamide] (7b)
Yield 553 mg, quantitative; ½a D20
ꢁ
+146.4 (c 1.0, H2O); dH (D2O)
144.66 (Cquat triazole), 124.51 (CH triazole), 102.01 (C1), 81.12
0
7.92 (s, 1H, H triazole), 5.24–4.94 (m, 7H, H1, H0 ), 4.51 (m, 1H,
(C4), 73.08–71.90 (C2, C3, C5), 63.22 and 60.33 (C6, C6 ), 52.29
1
CHNH2), 4.38 (s, 2H, 2H0), 4.11 (s, 2H, CH2NH), 3.95–3.45 (m,
63H), 3.27 (m, 14H), 3.12 (s, 1H, H0), 3.07 (s, 1H, H0), 2.05 (m, 1H,
CH(CH3)2), 0.87 (d, 3H, CH3), 0.85 (d, 3H, CH3); dC (D2O) 178.75
and 166.14 (CO), 143.79 (Cquat triazole), 125.77 (CH triazole),
100.68–98.85 (C1), 82.35–81.21 (C4), 73.38–69.98 (C2, C3, C5),
(CHNH2), 40.93 (CH2CHNH2), 34.50 (CH2NH), 24.11 (CH(CH3)2),
21.75 (CH3); m/z 1350.13 (calcd 1350.49 for [C51H85N5O35+Na]+),
1366.14 (calcd 1366.60 for [C51H85N5O3+K]+).
4.5.5. L-Proline-N-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)
methylamide] (6e)
64.12–62.95 (C6, C0 ), 59.71–58.40 (OCH3), 55.38 (CHNH2), 34.25
6
(CH2NH), 29.9 (CH(CH3)2), 17.62 (CH3), 17.08 (CH3); m/z (%)
1490.21 (1.4) (calcd 1490.32 for [C61H105N5O35+Na]+), 1504.22
(14.2) (calcd 1404.33 for [C62H107N5O35+Na]+), 1518.25 (68.3)
(calcd 1518.34 for [C63H109N5O35+Na]+), 1532.26 (14.7) (calcd
1532.35 for [C64H111N5O35+Na]+), 1546.25 (1.4) (calcd 1546.36
for [C65H113N5O35+Na]+).
Yield 564 mg, quantitative; dH (D2O) 7.83 and 7.72 (s, 1H, H tri-
azole), 5.05–4.87 (m, 7H, H1, H0 ), 4.52–4.43 (m, 3H, CHNH, CH2NH),
1
4.29–4.22 (m, 1H, H0), 4.09–4.01 (m, 1H, H0), 3.87–3.60 (m, 22H, H3,
H5, H6, H0), 3.60–3.37 (m, 16H, H2, H4, 2 ꢂ H0), 3.28 (m, 2H,
CH2NHCH), 3.04 (m, 1H, H0), 2.70 (m, 1H, H0), 2.33 (m, 1H,
CHHCHNH), 1.93 (m, 3H, CHHCHNH, CH2CH2NH); dC (D2O)

216
D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
4.6.3.
L
-Isoleucine-N-[(1-randomly methylated-b-
4.7. General procedure for the synthesis of ditopic b-CD
receptors 8a–f
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (7c)
Yield 558 mg, quantitative; ½a D20
ꢁ
+90.5 (c 1, H2O); dH (D2O) 7.92
(s, 1H, H triazole), 5.25–4.93 (m, 7H, H1, H0 ), 4.38 (d, 1H, CHNH2),
To a solution of 5a–f (0.23 mmol) in DMF (20 mL) was added 1
(0.5 mmol) and CuSO4ꢀ5H2O (0.45 mmol). Once the solution was
clear, sodium ascorbate (0.90 mmol) in H2O (2 mL) was added
dropwise over 15 min. The reaction mixture was vigorously stirred
and irradiated at 60 °C for 2 h under microwaves. DMF was then
evaporated. The powder was dissolved in aqueous ammonia
(8 wt %) and purified on a short silica gel column to remove the
copper salts. Evaporation of the solvent gave a pale yellow powder
which was purified by column chromatography using water as elu-
ant to give the expected compound as a white powder.
1
4.15 (m, 2H, CH2NH), 3.82 (m, 14H), 3.63–3.44 (m, 50H), 3.29 (m,
15H), 3.10 (m, 1H, H0), 2.82 (m, 1H, H0), 1.84 (m, 1H,
CH(CH3)(CH2CH3)), 1.35 (m, 1H, CH2CH3), 1.09 (m, 1H, CH2CH3),
0.83 (m, 3H, CH3), 0.77 (m, 3H, CH3); dC (D2O) 178.64–166.45
(CO), 144.29 (Cquat triazole), 127.60 (CH triazole), 100.69–98.89
(C1), 82.33–81.20 (C4), 72.74–69.98 (C2, C3, C5), 63.14 (C6), 59.58–
59.10 (OCH3), 58.33 (CHNH2), 36.31 (CH(CH3)(CH2CH3)), 34.07
(CH2NH), 24.37 (CH2CH3), 14.02 (CH3), 10.49 (CH3); m/z (%)
1504.29 (4.7) (calcd 1504.35 for [C62H107N5O35+Na]+), 1518.32
(29.7) (calcd 1518.36 for [C63H109N5O35+Na]+), 1532.33 (52.6)
(calcd 1532.37 for [C64H111N5O35+Na]+), 1546.35 (11.2) (calcd
1546.38 for [C65H113N5O35+Na]+), 1560.37 (1.9) (calcd 1560.39 for
[C66H115N5O35+Na]+).
4.7.1. a-N-(1-b-Cyclodextrinyl-1H-1,2,3-triazol-4-yl)-L-alanine-
[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (8a)
Yield 560 mg, quantitative; dH (D2O, 80 °C) 9.04 (s, 1H, H tria-
zole), 8.47 (s, 1H, H triazole), 5.63 (m, 14H, H1, H0), 5.08 (m, 3H,
CHNH, 2 ꢂ H0), 4.79 (CH2NH, H0 overlapped with HOD), 4.51–4.42
(m, 48H, H3, H5, H6), 4.22–4.13 (m, 26H, H2, H4, H0), 3.76 (t, 2H,
H0), 3.56 (m, 2H, H0), 2.07 (d, 3H, CH3); m/z 2519.34 (calcd
2519,82 for [C93H148N8O70+Na]+), 2535.30 (calcd 2535.93 for
[C93H148N8O70+K]+).
4.6.4. L-Leucine-N-[(1-randomly methylated-b-cyclodextrinyl-
1H-1,2,3-triazol-4-yl)methylamide] (7d)
Yield 558 mg, quantitative; ½a D20
ꢁ
+82.2 (c 1.0, H2O); dH (D2O)
7.91 (s, 1H, H triazole), 5.14–4.93 (m, 7H, H1, H0 ), 4.53 (d, 3H,
1
CHNH2, CH2NH), 4.36 (m, 1H, H0), 4.21 (m, 1H, H0), 3.81–3.43 (m,
61H), 3.27 (m, 16H), 3.07 (m, 1H, H0), 3.05 (m, 1H, H0), 2.73 (m,
1H, CH(CH3)2), 1.64 (m, 2H, CH2CHNH2), 0.81 (d, 6H, 2 ꢂ CH3); dC
(D2O) 178.74–166.32 (CO), 143.86 (Cquat triazole), 125.40 (CH tria-
zole), 100.69–98.87 (C1), 82.37–81.25 (C4), 73.34–69.95 (C2, C3, C5),
4.7.2. a-N-(1-b-Cyclodextrinyl-1H-1,2,3-triazol-4-yl)-L-valine-
[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (8b)
Yield 573 mg, quantitative; dH (D2O, 80 °C) 9.06 (s, 1H, H tria-
64.06–62.80 (C6, C6 ), 59.60–58.72 (OCH3), 58.35 (CHNH2), 52.01
zole), 8.49 (s, 1H, H triazole), 5.64 (m, 14H, H1, H0 ), 5.21 (m, 3H,
0
1
(CH(CH3)2), 40.15 (CH2CHNH2), 34.25 (CH2NH), 23.97 (CH3),
21.64 (CH3); m/z (%) 1504.21 (2.2) (calcd 1504.35 for [C62H107N5
O35+Na]+), 1518.24 (17.7) (calcd 1518.36 for [C63H109N5O35+Na]+),
1532.26 (61.6) (calcd 1532.37 for [C64H111N5O35+Na]+), 1546.27
(14.8) (calcd 1546.38 for [C65H113N5O35+Na]+), 1560.27 (3.7) (calcd
1560.39 for [C66H115N5O35+Na]+).
CHNH, 2 ꢂ H0), 5.09 (s, 2H, CH2NH), 4.79 (H0 overlapped with
HOD), 4.44 (m, 48H, H3, H5, H6), 4,23–4,15 (m, 26H, H2, H4, H0),
3.85–3.72 (m, 2H, H0), 3.62–3.28 (m, 2H, H0), 2.78 (m, 1H,
CH(CH3)2), 1.58–1.54 (m, 6H, 2 ꢂ CH3); m/z 2547.70 (calcd
2547.85 for [C95H152N8O70+Na]+), 2563.68 (calcd 2563.96 for
[C95H152N8O70+K]+).
4.6.5.
L
-Proline-N-[(1-randomly methylated-b-cyclodextrinyl-
4.7.3. a-N-(1-b-Cyclodextrinyl-1H-1,2,3-triazol-4-yl)-L-
1H-1,2,3-triazol-4-yl)methylamide] (7e)
isoleucine-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-
yl)methylamide] (8c)
Yield 552 mg, quantitative; ½a D20
ꢁ
+85.1 (c 0.5, H2O); dH (D2O)
0
7.91 (s, 1H, H triazole), 5.24–4.93 (m, 7H, H1, H1 ), 4.43 (m, 3H,
CHNH2, CH2NH), 4.09 (m, 2H, 2 ꢂ H0), 3.80–3.43 (m, 61H), 3.27
(m, 16H), 3.12 (s, 1H, H0), 3.04 (m, 1H, H0), 2.75 (m, 2H, CH2NHCH),
1.92 (m, 4H, 2 ꢂ CH2); dC (D2O) 169.51–166.32 (CO), 143.84 (Cquat
triazole), 125.60 (CH triazole), 100.67–98.68 (C1), 81.37–77.79 (C4),
Yield 573 mg, quantitative; dH (D2O, 80 °C) 9.05 (s, 1H, H tria-
zole), 8.47 (s, 1H, H triazole), 5.82–5.56 (m, 14H, H1, H0), 4.79 (m,
CHNH, CH2NH, H0 overlapped with HOD), 4.45 (m, 48H, H3, H5,
H6), 4.17 (m, 26H, H2, H4, H0), 3.75 (m, 2H, H0), 3.57–3.50 (m, 2H,
H0), 2.56 (m, 1H, CHCHNH), 2.07 (m, 1H, CHHCH3), 1.81 (m, 1H,
CHHCH3), 1.48 (m, 6H, 2 ꢂ CH3); m/z 2561.40 (calcd 2561.86 for
[C96H154N8O70+Na]+), 2577.38 (calcd 2577.97 for [C96H154N8
O70+K]+).
0
72.82–70.03 (C2, C3, C5), 64.03–61.82 (C6, C6 ), 59.76–58.77 (OCH3),
58.33 (CHNH2), 46.39 (CH2NHCH), 34.62 (CH2NH), 29.64 (CH2),
23.68 (CH2); m/z (%) 1502.23 (11.0) (calcd 1502.31 for [C62H105N5
O35+Na]+), 1516.25 (58.9) (calcd 1516.32 for [C63H107N5O35+Na]+),
1530.26 (14.0) (calcd 1530.33 for [C64H19N5O35+Na]+), 1544.25
(8.4) (calcd 1544.34 for [C65H111N5O35+Na]+), 1558.25 (7.6) (calcd
1558.35 for [C66H113N5O35+Na]+).
4.7.4. a-N-(1-b-Cyclodextrinyl-1H-1,2,3-triazol-4-yl)-L-leucine-
[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (8d)
Yield 583 mg, quantitative; dH (D2O, 80 °C) 8.40 (s, 1H, H tria-
zole), 7.74 (s, 1H, H triazole), 5.04–4.86 (m, 14H, H1, H1 ), 4.47
0
4.6.6.
L
-Phenylalanine-N-[(1-randomly methylated-b-
(m, 2H, CHNH, H0), 4.39 (s, 1H, H0), 4.35 (m, 2H, 2 ꢂ H0), 4.08 (m,
2H, CH2NH), 3.75 (m, 48H, H3, H5, H6), 3.50 (m, 30H, H2, H4, H6,
H06), 3.02 (m, 2H, 2 ꢂ H0), 2.21 (m, 1H, CHCHNH), 1.56 (m, 2H,
CH2CHNH), 0.87 (t, J = 6.0 Hz, 3H, CH3CH), 0.80 (d, J = 6.0 Hz, 3H,
CH3CH); m/z 2561.38 (calcd 2561.86 for [C96H154N8O70+Na]+),
2577.35 (calcd 2577.97 for [C96H154N8O70+K]+).
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (7f)
Yield 570 mg, quantitative; ½a D20
ꢁ
+80.5 (c 1.0, H2O); dH (D2O)
7.19–7.05 (m, 6H, Ar-H, H triazole), 5.29–4.95 (m, 7H, H1, H0 ), 4.48
1
(m, 1H, CHNH2), 4.24 (m, 1H, H0), 4.10 (m, 1H, H0), 3.88 (m, 2H,
CH2NH), 3.56 (m, 59H), 3.29 (m, 18H), 3.02 (m, 4H, 2 ꢂ H0,
CH2-Ar); dC (D2O) 171.32 (CO), 144.08 (Cquat triazole), 136.49 (Cquat
Ar), 131.91, 131.36 and 130.05 (Ar), 126.70 (CH triazole), 103.47–
101.75 (C1), 86.04–84.01 (C4), 75.63–72.39 (C2, C3, C5), 66.61–
4.7.5. a-N-(1-b-Cyclodextrinyl-1H-1,2,3-triazol-4-yl)-L-proline-
[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (8e)
0
65.62 (C6, C6 ), 62.24–61.69 (OCH3), 60.82 (CHNH2), 39.67
Yield 575 mg, quantitative; dH (D2O, 80 °C) 8.39 (s, 1H, H tria-
(CH2-Ar), 36.46 (CH2NH); m/z (%) 1552.24 (12.9) (calcd 1552.23 for
[C66H107N5O35+Na]+), 1566.28 (63.6) (calcd 1566.24 for [C67H109N5
O35+Na]+), 1580.28 (17.7) (calcd 1580.25 for [C68H111N5O35+Na]+),
1594.28 (3.5) (calcd 1594.26 for [C69H113N5O35+Na]+), 1608.28
(2.3) (calcd 1608.27 for [C70H115N5O35+Na]+).
zole), 7.82 (s, 1H, H triazole), 5.06–4.87 (m, 14H, H1, H0 ), 4.58 (s,
1
1H, H0), 4.53 (s, 1H, H0), 4.47 (m, 1H, CHNCO), 4.46 (s, 1H, H0),
4.39 (s, 1H, H0), 4.11 (m, 2H, CH2NH), 3.88 (m, 48H, H3, H5, H6),
3.45 (m, 28H, H2, H4, 4 ꢂ H0), 3.03 (m, 4H, CH2N, 2 ꢂ H0), 2.70 (m,
2H, 2H0), 2.25 (m, 1H, CH2CHN), 1.80 (m, 3H, CH2CHN, CH2CH2N);

D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
217
m/z 2545.63 (calcd 2545.83 for [C95H150N8O70+Na]+), 2561.60
4.8.3.
triazol-4-yl)-
a
-N-(1-Randomly methylated-b-cyclodextrinyl-1H-1,2,3-
-isoleucine-[(1-randomly methylated-b-
(calcd 2561.94 for [C95H150N8O70+K]+).
L
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (9c)
Yield 1.08 g, quantitative; ½a D23
ꢁ
+53.24 (c 0.2, H2O). dH (D2O) 8.44
(s, 1H, H triazole), 7.85 (s, 1H, H triazole), 5.14 (m, 7H, H1, H1 ), 4.93
0
4.7.6. a-N-(1-b-Cyclodextrinyl-1H-1,2,3-triazol-4-yl)-L-
phenylalanine-[(1-b-cyclodextrinyl-1H-1,2,3-triazol-4-yl)
methylamide] (8f)
Yield 590 mg, quantitative; dH (D2O, 80 °C) 8.30 (s, 1H, H triazole),
7.22–7.11 (m, 6H, H triazole, Ar-H), 5.07–4.88 (m, 14H, H1, H1 ), 4.48
0
(m, 7H, H1, H1 ), 4.39 (m, 3H, CHNH, CH2NH), 4.31 (m, 2H, H0), 4.07
(m, 2H, H0), 3.83 (m, 22H), 3.52–3.41 (97H), 3.26 (m, 35H), 3.00 (m,
4H, H0), 1.86 (m, 1H, CH(CH3)(CH2CH3)), 1.44 (m, 1H, CH2CH3), 1.13
(m, 1H, CH2CH3), 0.78 (m, 6H, 2 ꢂ CH3); dC (DMSO-d6) 176.43–
142.81 (2CO, 2Cquat triazole), 128.48 (CH triazole), 124.41 (CH tri-
azole), 102.20–99.72 (C1), 83.25–79.64 (C4), 73.55–70.62 (C2, C3,
0
(m, 2H, CHNH, H0), 4.16 (m, 2H, CH2NH), 4.12 (m, 1H, H0), 3.74 (m,
50H, H3, H5, H6, 2 ꢂ H0), 3.48 (m, 28H, H2, H4, 4 ꢂ H0), 3.15–2.92
(m, 4H, 4 ꢂ H0), 2.78 (d, J = 12.0 Hz, 1H, CH2CHNH), 2.48 (d,
J = 12.0 Hz, 1H, CH2CHNH); m/z 2595.71 (calcd 2595.85 for
[C99H152N8O70+Na]+), 2611.69 (calcd 2611.82 for [C99H152N8
O70+K]+).
C5), 64.75–62.72 (C6, C0 ), 60.91–58.43 (OCH3), 56.85 (CHNH),
6
37.90 (CH(CH3)(CH2CH3)), 34.52 (CH2NH), 24.82 (CH2CH3), 15.79
(CH3), 11.28 (CH3); m/z (%) 2897.84 (4.7) (calcd 2898.24 for [C120
H202N8O70+Na]+), 2911.87 (19.9) (calcd 2912.25 for [C121H204
N8O70+Na]+), 2926.11 (45.3) (calcd 2925.91 for [C122H206N8O70+-
Na]+), 2939.94 (23.9) (calcd 2940.29 for [C123H208N8O70+Na]+),
2953.96 (6.2) (calcd 2954.30 for [C124H210N8O70+Na]+).
4.8. General procedure for the synthesis of ditopic randomly
methylated b-CD receptors 9a–f
4.8.4.
triazol-4-yl)-
a
-N-(1-Randomly methylated-b-cyclodextrinyl-1H-1,2,3-
-leucine-[(1-randomly methylated-b-
To a solution of 5a–f (0.37 mmol) in MeOH (30 mL) was added 2
(0.75 mmol) and CuSO4ꢀ5H2O (0.75 mmol). Once the solution was
clear, sodium ascorbate (1.50 mmol) in H2O (1.5 mL) was added
dropwise over 15 min. The reaction mixture was vigorously stirred
and irradiated at 60 °C for 2 h under microwave irradiation. The
MeOH was then evaporated. The resulting solid was dissolved in
aqueous ammonia (8 wt %) and purified by column chromatogra-
phy with water as eluent. Evaporation of the solvent gave a pale
yellow powder.
L
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (9d)
Yield 1.08 g, quantitative; ½a D23
ꢁ
+32.46 (c 0.2, H2O). dH (D2O) 8.44
(s, 1H, H triazole), 7.82 (s, 1H, H triazole), 5.14 (m, 7H, H1, H0 ), 4.92
1
(m, 7H, H1, H01), 4.44 (m, 3H, 2H0, CHNH), 4.21 (m, 2H, CH2NH), 4.08
(m, 2H, H0), 3.83 (m, 28H), 3.61–3.41 (94H), 3.26 (m, 32H), 2.99 (m,
4H, H0), 1.54 (m, 3H, CH(CH3)2, CH2CHNH2), 0.81 (d, 6H, 2 ꢂ CH3);
dC (DMSO-d6) 176.27–142.57 (2 CO, 2 Cquat triazole), 128.53 (CH
triazole), 125.14 (CH triazole), 102.18–100.41 (C1), 83.28–79.44
(C4), 73.24–70.58 (C2, C3, C5), 65.74–60.49 (C6, C0 ), 60.00–58.76
6
4.8.1.
a-N-(1-Randomly methylated-b-cyclodextrinyl-1H-1,2,3-
(OCH3), 51.00 (CHNH), 41.70 (CH2CHNH2), 34.86 (CH2NH), 24.95
(CH(CH3)2), 23.62 (CH3), 21.85 (CH3); m/z (%) 2898.31 (3.4) (calcd
2898.24 for [C120H202N8O70+Na]+), 2912.07 (17.4) (calcd 2912.25
for [C121H204N8O70+Na]+), 2926.11 (46.9) (calcd 2926.27 for
[C122H206N8O70+Na]+), 2940.13 (25.7) (calcd 2940.29 for [C123H208
N8O70+Na]+), 2954.14 (6.6) (calcd 2954.30 for [C124H210
N8O70+Na]+).
triazol-4-yl)-
L
-alanine-[(1-randomly methylated-b-
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (9a)
Yield 1.06 g, quantitative; ½a D22
ꢁ
+53.2 (c 0.2, H2O). dH (D2O): dH
7.82 (s, 1H, H triazole), 7.39 (s, 1H, H triazole), 5.13 (m, 7H, H1,
0
0
H1 ), 4.92 (m, 7H, H1, H1 ), 4.41 (s, 2H, H0), 4.21 (s, 3H, 2H0, CHNH),
4.06 (s, 2H, CH2NH), 3.85 (m, 28H), 3.52–3.42 (89H), 3.26 (m, 28H),
2.98 (m, 9H), 2.43 (m, 4H, H0), 1.30 (m, 3H, CH3); dC (DMSO-d6)
177.06–142.70 (2CO, 2Cquat triazole), 125.41 (CH triazole), 115.34
(CH triazole), 102.21–99.14 (C1), 83.39–79.67 (C4), 73.98–70.69
4.8.5.
triazol-4-yl)-
a
-N-(1-Randomly methylated-b-cyclodextrinyl-1H-1,2,3-
-proline-[(1-randomly methylated-b-
L
(C2, C3, C5), 65.22–63.69 (C6, C0 ), 62.59–58.87 (OCH3), 48.81
6
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (9e)
Yield 1.07 g, quantitative; ½a D23
ꢁ
+94.66 (c 0.2, H2O). dH (D2O) 8.42
(CHNH), 28.67 (CH2NH), 19.04 (CH3). m/z (%) 2855.87 (4.6) (calcd
2856.19 for [C117H196N8O70+Na]+), 2869.91 (20.9) (calcd 2870.21
for [C118H198N8O70+Na]+), 2883.95 (46.5) (calcd 2884.22 for
[C119H202N8O70+Na]+), 2897.97 (22.9) (calcd 2898.24 for [C120H202
N8O70+Na]+), 2912.00 (5.1) (calcd 2912.25 for [C121H204N8
O70+Na]+).
(s, 1H, H triazole), 7.85 (s, 1H, H triazole), 5.13 (m, 7H, H1, H0 ), 4.93
1
(m, 7H, H1, H01), 4.46 (s, 2H, CH2NH), 4.40 (m, 3H, 2H0, CHNH), 4.15
(m, 2H, H0), 3.82 (m, 26H), 3.52–3.42 (93H), 3.26 (m, 35H), 2.99 (m,
4H, H0), 2.23 (m, 1H, CH2NCH), 1.86 (m, 3H, CH2CHN, CH2NCH),
1.44 (m, 2H, CH2CH2CH2); dC (DMSO-d6) 176.59–143.98 (2CO,
2Cquat triazole), 130.62 (CH triazole), 124.70 (CH triazole),
102.44–100.61 (C1), 83.08–79.51 (C4), 73.17–71.58 (C2, C3, C5),
4.8.2.
a-N-(1-randomly methylated-b-cyclodextrinyl-1H-1,2,3-
65.08–62.87 (C6, C0 ), 60.78–58.58 (OCH3), 53.52 (CHN), 34.94
triazol-4-yl)-
L
-Valine-[(1-randomly methylated-b-
6
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (9b)
(CH2NH), 29.64 (CH2NCH), 26.68 (CH2CHN), 24.99 (CH2CH2CH2);
m/z (%) 2881.82 (3.3) (calcd 2882.21 for [C119H198N8O70+Na]+),
2895.86 (16.8) (calcd 2896.22 for [C120H200N8O70+Na]+), 2909.89
(48.2) (calcd 2910.24 for [C121H202N8O70+Na]+), 2923.90 (25.8)
(calcd 2924.25 for [C122H204N8O70+Na]+), 2937.91 (6.0) (calcd
2938.27 for [C123H206N8O70+Na]+).
Yield 1.07 g, quantitative; ½a D23
ꢁ
+117.26 (c 0.2, H2O). dH (D2O)
8.44 (s, 1H, H triazole), 7.84 (s, 1H, H triazole), 5.23 (m, 7H, H1,
0
H1 ), 4.92 (m, 7H, H1, H0 ), 4.41 (m, 3H, CH2NH, CHNH), 4.21 (m,
1
2H, H0), 4.09 (m, 2H, H0), 3.82 (m, 23H), 3.53–3.42 (96H), 3.25 (m,
35H), 2.99 (m, 4H, H0), 2.07 (m, 1H, CH(CH3)2), 0.86 (m, 6H,
2 ꢂ CH3); dC (DMSO-d6) 176.45–142.81 (2CO, 2Cquat triazole),
128.25 (CH triazole), 124.01 (CH triazole), 102.14–99.38 (C1),
4.8.6.
a
-N-(1-Randomly methylated-b-cyclodextrinyl-1H-1,2,3-
-phenylalanine-[(1-randomly methylated-b-
83.48–79.20 (C4), 73.70–70.64 (C2, C3, C5), 64.83–62.38 (C6, C0 ),
triazol-4-yl)-
L
6
60.85–58.41 (OCH3), 53.21 (CHNH), 34.55 (CH2NH), 32.11
(CH(CH3)2), 19.87 (CH3), 18.34 (CH3); m/z (%) 2883.94 (3.2) (calcd
2884.22 for [C119H200N8O70+Na]+), 2897.96 (18.3) (calcd 2898.24
for [C120H202N8O70+Na]+), 2911.98 (49.5) (calcd 2912.25 for
[C121H204N8O70+Na]+), 2926.00 (23.9) (calcd 2926.27 for [C122H206
N8O70+Na]+), 2940.00 (5.1) (calcd 2940.29 for [C123H208N8
O70+Na]+).
cyclodextrinyl-1H-1,2,3-triazol-4-yl)methylamide] (9f)
Yield 1.09 g, quantitative; ½a D23
ꢁ
+47.33 (c 0.2, H2O). dH (D2O) 8.29
(s, 1H, H triazole), 7.20 (m, 6H, H triazole, 5 ꢂ H Ar), 5.14 (m, 7H, H1,
H01), 4.91 (m, 7H, H1, H01), 4.41 (m, 1H, CHNH), 4.20 (m, 2H, H0), 4.07
(m, 2H, H0), 3.91 (s, 2H, CH2NH), 3.80 (m, 29H), 3.55–3.39 (92H),
3.25 (m, 33H), 3.11 (m, 2H, H0), 2.97 (m, 2H, H0), 2.41 (m, 1H,
CH2-Ar), 2.07 (m, 1H, CH2-Ar). dC (DMSO-d6) 177.98–137.92 (2CO,

218
D. N. Tran et al. / Carbohydrate Research 346 (2011) 210–218
Nuzillard, J.-M.; Peulon-Agasse, V.; Cardinaël, P.; Bouillon, J.-P. J. Chromatogr., A
2009, 1216, 4051–4062.
2Cquat triazole, Cquat Ar), 165.99 (CH triazole), 163.58 (CH triazole),
129.71, 128.67, 126.89 (CH Ar), 102.26–99.54 (C1), 83.44–79.47
2. (a) W.-D. Woggon, A. Schlatter, H. Wang, b-Cyclodextrinlinked Ru Complexes for
Oxidations and Reductions, in: R. van Eldik (Ed.), Advances in Inorganic
Chemistry, vol. 60, Academic Press, Netherlands, 2008, pp. 31–58; (b)
Schlatter, A.; Woggon, W.-D. Adv. Synth. Catal. 2008, 350, 995–1000. and
references cited therein.
(C4), 74.24–70.68 (C2, C3, C5), 64.83–62.74 (C6, C0 ), 58.97–54.99
6
(OCH3), 3.54 (CHNH), 33.88 (CH2NH), 28.86 (CH2-Ar); m/z (%)
2931.99 (5.2) (calcd 2932.22 for [C123H200N8O70+Na]+), 2945.99
(21.2) (calcd 2946.24 for [C124H202N8O70+Na]+), 2960.03 (47.9)
(calcd 2960.25 for [C125H204N8O70+Na]+), 2974.03 (20.9) (calcd
2974.27 for [C126H206N8O70+Na]+), 2988.04 (6.7) (calcd 2988.29 for
[C127H208N8O70+Na]+).
3. Cucinotta, V.; Giuffrida, A.; Grasso, G.; Maccarrone, G.; Messina, M.; Vecchio, G. J.
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Acknowledgments
This work was supported by the Centre National de la Recher-
che Scientifique (CNRS). Dr. D. N. Tran is grateful to the Agence
Nationale de la Recherche for financial support (ANR-09-BLAN-
0194-02). Roquette Frères (Lestrem, France) is gratefully acknowl-
edged for generous gifts of cyclodextrins. We thank Dr. C. Flahaut
and J. Hachani for mass spectrometry analyses and Pr. Eric Deniau
for use of the polarimeter.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.11.024.
6. Kim, H.-Y.; Sohn, J.; Wijewickrama, G. T.; Edirisinghe, P.; Gherezghiher, T.;
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Thatcher, G. R. J. Bioorg. Med. Chem. 2010, 18, 809–821.
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