New cup-shaped α-cyclodextrin derivatives and a study of their catalytic properties in oxidation reactions

Article abstract of DOI:10.1016/j.tet.2007.06.018

A series of new α-cyclodextrin derivatives with a substituted propylene bridge attached to the 6-O's of the A,D-glucose units are reported. The compounds were prepared from the known 6^A,6^D-di-O-(prop-2-methylidene-1,3-dienyl)-hexadeca-O-benzyl-α-cyclodextrin, which was transformed into 6^A,6^D-di-O-(prop-2-methyl-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-formyl-2-hydroxy-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-aminomethyl-2-hydroxy-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-hydroxymethylidene-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-formyl-1,3-dienyl)-α-cyclodextrin, 6^A,6^D-di-O-(prop-2-carboxy-1,3-dienyl)-α-cyclodextrin and 6^A,6^D-di-O-(prop-2-methoxycarbonyl-1,3-dienyl)-α-cyclodextrin. The new compounds were evaluated for their ability to affect amine and alcohol oxidations in the presence of hydrogen peroxide.

Full text of DOI:10.1016/j.tet.2007.06.018

Tetrahedron 63 (2007) 8872–8880
New cup-shaped a-cyclodextrin derivatives and a study
of their catalytic properties in oxidation reactions
*
Oscar Lopez Lopez, Lavinia Marinescu and Mikael Bols
Department of Chemistry, University of Aarhus, Langelandsgade 140, DK-8000, Aarhus, Denmark
Received 16 February 2007; revised 18 May 2007; accepted 7 June 2007
Available online 10 June 2007
Abstract—A series of new a-cyclodextrin derivatives with a substituted propylene bridge attached to the 6-O’s of the A,D-glucose units are
reported. The compounds were prepared from the known 6 ,6 -di-O-(prop-2-methylidene-1,3-dienyl)-hexadeca-O-benzyl-a-cyclodextrin,
A
D
A
D
A
D
which was transformed into 6 ,6 -di-O-(prop-2-methyl-1,3-dienyl)-a-cyclodextrin, 6 ,6 -di-O-(prop-2-formyl-2-hydroxy-1,3-dienyl)-
A
a-cyclodextrin, 6 ,6 -di-O-(prop-2-aminomethyl-2-hydroxy-1,3-dienyl)-a-cyclodextrin, 6 ,6 -di-O-(prop-2-hydroxymethylidene-1,3-
D
A
D
A
dienyl)-a-cyclodextrin, 6 ,6 -di-O-(prop-2-formyl-1,3-dienyl)-a-cyclodextrin, 6 ,6 -di-O-(prop-2-carboxy-1,3-dienyl)-a-cyclodextrin
D
A
D
A
D
and 6 ,6 -di-O-(prop-2-methoxycarbonyl-1,3-dienyl)-a-cyclodextrin. The new compounds were evaluated for their ability to affect amine
and alcohol oxidations in the presence of hydrogen peroxide.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
of the primary hydroxyls in position 6A and 6D of perbenzyl-
ated cyclodextrins, since it makes it possible to work with
these molecules in protected form.
Supramolecular chemistry refers to the area of chemistry,
which focuses on the non-covalent bonding interactions of
molecules. In the last decades we have seen an impressive
advance in the field and a continuously growing awareness
of the importance of this topic. The study of how molecules
can organise other molecules in such a way that they are in-
duced to react, when they otherwise would not, is a field that
One significant problem with many cyclodextrin-based
enzyme models may have been too much flexibility. The first
attempt to overcome the flexibility problems was made by
6
Tabushi et al. by synthesising a mixture of A,C and A,D
capped cyclodextrins on the primary rim. Despite consider-
1
2
7
was pioneered by the research groups of Breslow, Bender,
Tabushi and others, but nevertheless is still in its infancy.
able effort and several well-defined protocols, only poor
regioselectivities and low yields were reported for the prepa-
ration of different bridged cyclodextrins. Using a new meth-
3
8
Cyclodextrins are popular building blocks in supramolecular
chemistry and enzyme modelling due to their ready avail-
ability, their ability to bind various compounds into their
hydrophobic cavities, their low-toxicity and their water
odology, Sina €y and collaborators on the other hand made a
A,D bridged compound very efficiently. We also reported
the synthesis of bridged-cyclodextrin derivatives 1–3
1
0–13
(Fig. 1),
which werefoundtofunctionasenzymemodels.
4
,5
solubility. The native compounds have major applications
in pharmacy, food industry, cosmetics, agrochemistry and
analytical chemistry, but when one wishes to use cyclo-
The bridged ketocyclodextrins 2 and 3 (Fig. 1) were found
to catalyse epoxidation through intermediate dioxiranes
6
1
2,13
dextrins as building blocks, one encounters the inherent
problems of dealing in a specific way with 18 or more
hydroxyl groups. While synthetic schemes to solve some
formed in the presence of persulfates and they can
increase the oxidation of anilines to nitrobenzenes in the
7
of these problems have emerged, generally speaking, syn-
thetic cyclodextrin chemistry is nevertheless a relatively
HO
O
O
O
O
OH
NC
A
CN
D
O
O
A
O
O
D
8
complex and low-yielding endeavour. Furthermore, many
modifications are effectively impossible to make. It was
A
D
α
9
therefore very important progress when Sina €y et al. discov-
ered that DIBAL can effect regioselective de-O-benzylation
(OH)16,19
(OH)16,19
(OH)16,19
1
2
3
*
Corresponding author. Tel.: +45 89423963; fax: +45 86196199; e-mail:
mb@chem.au.dk
Figure 1. Examples of some cyclodextrin-based artificial enzymes.
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.06.018

O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
8873
1
4
presence of hydrogen peroxide with a k /k
up to 1070.
anhydrous toluene and inert atmosphere. Coupling of diol
5 with methallyl dichloride (1.1 equiv) in the presence of
cat uncat
Our bridged ketoester-cyclodextrins 3 proved to be remark-
ably good artificial enzymes for benzyl alcohol oxidations
into aldehydes or ketones with rate increase of up to
1
2
NaH afforded known bridged-alkene 7 in an 84% yield
(Scheme 1). Compound 7 turned out to be a valuable starting
material with broad applicability for the preparation of
a wide range of bridged-cyclodextrin derivatives. Attempts
to carry out standard hydrogenolysis on 7 to afford derivative
8 led to the title compound together with derivative 9, as a re-
sult of the bridge opening; this enhancement of reactivity in
this position can be explained by the allylic nature. This
problem was overcome by first reducing the double bond us-
ing hydrogen and Wilkinson’s catalyst, followed by standard
hydrogenolysis for the removal of the O-benzyl groups
4
15
6
.3ꢀ10 in the best case.
In this article we present the synthesis of a series of new
capped or bridged cyclodextrins similar to 2 and 3 but
with a variety of functional groups in the bridge, and report
their ability to catalyse oxidation reactions.
2
. Results and discussion
(
Scheme 1). The presence of the methyl group in the bridge
Starting material for all our compounds was commercial
a-cyclodextrin 4. This compound was subjected to per-O-
benzylation using BnCl in the presence of NaH and
DMSO as solvent (Scheme 1). Original methodology for
perbenzylation of a- and b-cyclodextrins was reported by
scaffold can increase the hydrophobicity of the cyclodextrin
cavity, and thus, might enhance binding affinities of unpolar
substrates.
Dihydroxylation of the double bond of 7 was carried out by
treatment with NMO and catalytic OsO in aq acetone
1
6
17
12
Takahashi and Sato, respectively. Full protection of the
4
1
6
cyclomaltohexaose was accomplished using benzyl bro-
mide and DMF as solvent and the product was isolated by
column chromatography; on the contrary, per-O-benzylation
(Scheme 2), although addition of NaIO was found to be im-
4
portant for the reaction to proceed faster. Bridged 1,2-glycol
10 was isolated in an 87% yield after column chromato-
graphy, together with a small amount (4%) of 13; this glycol
was previously used by us as a non-isolated intermediate
1
7
of cyclomaltoheptaose was carried out with benzyl chlo-
ride and DMSO as solvent, and isolation of the final product
involved precipitation with a mixture of acetone–MeOH.
1
2
for the synthesis of ketone 13. Attempts to oxidise 10 to
the corresponding a-hydroxy aldehyde 11 using Dess–
Martin periodinane failed, and despite the smooth conditions
associated with this oxidation, an oxidative cleavage took
place, ketone 13 being the major compound detected
in MALDI spectrum; only traces of the desired 11 were de-
tected. This sensitivity of 1,2-glycols towards oxidative
In our hands, full protection of 4 was furnished by using
benzyl chloride and DMSO as solvent to give derivative 5
in a 91% yield after column chromatography. Selective
A,D di-O-debenzylation of 5 was carried out following the
1
8,19
original methodology reported by Sina €y ,
modifications recently reported by us.
including the
2
0
21
cleavage was previously reported by Isobe et al. when
using different oxidants, rather than Dess–Martin reagent.
This problem was overcome by replacing the oxidant with
Thus, diol 6 was prepared in an 86% yield after column
chromatography upon treatment of 4 with DIBAL-H in
2
2,23
sulfur trioxide–Py complex,
under conditions similar
HO
D
OH
A
DIBAL-H,toluene
BnCl
NaH, DMSO
N , rt, overnight
α
α
α
4 Å MS, rt, N
86%
2
2
(OH)18
91%
(OBn)18
(OBn)16
Cl
4
5
6
Cl
NaH, DMF, rt
4%
8
Me
HO
O
O
O
O
O
Me
H
Me
D
A
D
A
H2
D
A
α
+
α
Pd(OH) −C
2
α
1
:1 EtOAc−MeOH
TFA (cat)
83%
(OH)16
(OH)16
(OBn)16
9
8
7
1
) H , Wilkinson
2
catalyst
) H , Pd/C
2
2
8
Scheme 1. Synthesis of 8.

8874
O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
OH
OH
O
O
O
O
O
O
OH
O
D
A
D
A
D
A
NMO, NaIO4
SO −Py complex
3
OsO , 10:1 Me CO−H O
DMSO, Et
N, rt, 3 h
3
4
2
2
8
7%
97%
(
OBn)16
(OBn)16
(OBn)16
11
7
10
NaIO −SiO
H , Pd/C
2
4
2
CH Cl
EtOAc−MeOH
2
2
TFA
O
O
NC OH
O
O
O
O
O
O
OH
D
A
D
A
D
A
KCN, NH Cl
4
2
:1:1 H O-Et O-MeOH
2
2
7
1%
(OBn)16
(OBn)16
(OH)16
14
13
12
H , Pd/C
2
EtOAc−MeOH
TFA
O
H N
O
OH
3
CF
A
3
COO
D
(OH)16
15
Scheme 2. Synthesis of 12 and 15.
to Swern oxidation, with compound 11 being obtained in
almost quantitative yield (Scheme 2). The presence of the
a-located hydroxyl group in 11 is expected to enhance
electrophilicity of the aldehyde moiety, which might be of
interest either in synthesis or in related catalysts. Deprotec-
tion under standard hydrogenolysis conditions afforded
derivative 12.
Another synthetic route for derivatisation of this family of
cyclodextrins was regioselective hydroxylation of alkene
7; thus, hydroboration–oxidation process at room tempera-
2
5–27
ture employing an excess of 9-BBN
for the hydrobora-
tion step furnished primary alcohol derivative 16 as the only
isolated product in an 81% yield; hydrogenolysis afforded
fully O-unprotected derivative 17 in 83% yield (Scheme 3).
Attempts were also made to oxidise a-hydroxy aldehyde 11
to the corresponding carboxylic acid, which was obtained as
the major compound as deduced from MALDI spectrum of
the crude reaction; nevertheless, attempts to purify it by
column chromatography led to a partial decomposition.
When alcohol 16 was treated with Dess–Martin periodinane,
the corresponding aldehyde 18 was obtained in moderate
yield (65%) after column chromatography. The presence
1
of the aldehyde moiety was supported by H NMR (broad
singlet at 9.24 ppm), C NMR (200.9 ppm) and IR (2869,
1
3
ꢁ
1
1726 cm ). In situ oxidation of the aldehyde with sodium
chlorite in a buffered medium gave access carboxylic
acid derivative 20, whose C NMR spectrum showed the
1
2
28
1
,2-Glycol 10 was also converted into known ketone 13 by
2
4
13
oxidative cleavage induced by silica-supported NaIO4, and
the latter was transformed into bridged cyanohydrin 14 in
good yield (71%) by treatment with an excess of KCN and
corresponding peak for the carboxylic residue (177.9 ppm);
deprotection under standard conditions gave 21 in a quantita-
tive yield (Scheme 3).
NH Cl (Scheme 2). The structure was supported by spectro-
4
1
3
scopic data; thus C NMR spectrum showed a signal at
1
ꢁ
1
19.0 ppm and the IR data showed a peak at 2250 cm
,
It is noteworthy to mention that fully unprotected aldehydes
12 and 19 present only small signals in NMR spectra corre-
sponding to the aldehyde motif; the reason is that the alde-
hyde moiety must be in equilibrium with the hemiacetalic
form, the equilibrium being shifted to the latter.
both compatible with the presence of a cyano moiety. Final
deprotection of the benzyl groups under standard hydro-
genolysis conditions did not afford the expected unprotected
cyanohydrin, but reduction of the cyano moiety took place
and amino derivative 15 was indeed obtained, probably in
equilibrium between the protonated and non-protonated
species.
Furthermore, treatment of readily-available carboxylic
acid derivative 20 with thionyl chloride afforded the

O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
8875
O
O
O
O
OH
O
O
OH
D
A
D
A
D
A
1
) 9-BBN, THF
) 3M aq NaOH, H O
H , Pd/C
2
2
1:1 EtOAc−MeOH
2
2
TFA (cat)
8
1%
(OBn)16
8
3%
(OH)16
(
OBn)16
7
16
17
Dess-Martin
periodinane
CH Cl
2
2
6
5%
O
O
O
O
O
O
D
A
D
A
H , Pd-C
2
1
:1 EtOAc−MeOH
TFA (cat)
(OBn)16
(OH)16
18
19
NaClO , NaH PO
4
2
2
2
-methylbut-2-ene
t
BuOH−THF−H O
2
5
6% (from 16)
O
O
H
O
O
O
MeOOC
H
O
MeOOC
HOOC
H
1
) SOCl2
H , Pd-C
D
A
D
A
D
A
2
2
) CH Cl −MeOH
1:1 EtOAc−MeOH
2
2
TFA (cat)
8
9%
Quant
(OBn)16
(OBn)16
(
OH)16
20
22
23
H , Pd-C
2
1
:1 EtOAc−MeOH
TFA (cat)
Quant
O
O
H
HOOC
D
A
(OH)16
21
Scheme 3. Synthesis of 17, 19, 21 and 23.
corresponding transient acyl chloride that was in situ cou-
pled with methanol to furnish the corresponding methyl ester
and were analysed using the usual equation:
2
2, isolated in an 89% yield after purification. Removal of
the benzyl groups provided 23 in a quantitative yield
Scheme 3).
S
V
cat ¼ V
m
S þ Km
(
where Vcat is the initial steady state rate of catalysed reac-
tion, Vm is the maximum rate and Km is the Michaelis–
Menten constant. The fit of the kinetics was found using
a Hanes plot shown in Figure 2, and Vm and Km were ob-
tained using non-linear regression fitting of the data to the
Michaelis equation above. From V , the value of k was
Unprotected cyclodextrin derivatives 12, 15, 17, 19, 21 and
3 were tested for catalysis in the hydrogen peroxide-medi-
ated oxidation of anilines and benzylic alcohols. While
no catalysis was found for oxidation of 4-methoxybenzyl al-
cohol to benzaldehyde by any of the compounds, 12, 19 and
2
1
4
15
m
cat
2
1 catalysed the oxidation of 2-hydroxyaniline into 2-ami-
calculated by division with the enzyme concentration. The
kinetic parameters are shown in Table 1.
nophenoxazin-2-one (Table 1). These oxidations followed
the Michaelis–Menten kinetic scheme:
Not surprisingly, the aldehyde 19 displayed the best activity
giving a kcat of 1.58ꢀ10
k1
ꢁ3 ꢁ1
kcat
s
which represents how much faster the reaction is occurring
and a k /k
ratio of 410,
cat uncat
S þ E%ES/E þ P
kꢁ1

8876
O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
Table 1. Kinetic data for the oxidation of 2-hydroxyaniline into 2-amino-
phenoxazin-2-one catalysed by the new cyclodextrins
showed that a compound containing an aldehyde substituent
displayed catalysis, while the other analogues showed much
smaller or no catalysis.
Reaction
catalyst
NH2
OH
N
O
NH2
O
H2O2
phosphate
4. Experimental section
pH 7
3
ꢁ1
)
Catalyst
k
cat (ꢀ10 s
K
m
k
cat/kuncat
4
.1. General
HO
O
NH2
OH
O
1
1
1
1
2
2
5
7
9
1
0.04ꢃ0.004
—
3.8ꢃ1.0
9
Solvents were distilled under anhydrous conditions. All re-
agents were used as purchased without further purification.
Evaporation was carried out in a rotatory evaporator. Glass-
HO
—
—
—
ware used for water-free reactions was dried for 2 h at
ꢂ
1
6
30 C before use. Columns were packed with silica gel
0 (230–400 mesh) as the stationary phase. TLC plates
—
—
(Merck, 60, F254) were visualised by spraying with cerium
1.58ꢃ0.08
0.30ꢃ0.05
10.2ꢃ1.0
3.5ꢃ1.1
410
60
sulfate (1%) and molybdic acid (1.5%) in 10% H SO and
2
4
1
13
heating until coloured spots appeared. H, C NMR and
COSY experiments were carried out with a Varian Mercury
COOH
4
00 instrument. Monoisotopic mass spectra (MALDI-TOF
COOMe
MS) were obtained on a Bruker Daltonics mass spectrometer
using an a-cyanohydroxycinnamic acid (a-CHCA) matrix.
Spectra were calibrated using a peptide calibration standard
solution.
23
—
—
—
—
means that no catalysis was observed.
A
D
inside the cyclodextrin cavity. It is likely that the aldehyde
works similarly to the previously reported ketones, where
we proposed that the carbonyl group binds hydrogen per-
oxide before reacting with bound amine. The corresponding
4.1.1. 6 ,6 -Di-O-(prop-2-methyl-1,3-dienyl)-a-cyclo-
A
D
dextrin (8). To a solution of 6 ,6 -di-O-(prop-2-methyl-
idene-1,3-dienyl)-hexadeca-O-benzyl-a-cyclodextrin (7)
(0.34 g, 0.13 mmol) in EtOAc (20 mL) was added Wilkin-
son’s catalyst (108 mg) and the corresponding mixture was
stirred under hydrogen atmosphere (1 atm) for 2 days.
Then, it was concentrated to dryness and the residue was
purified by column chromatography (pentane/1:5
EtOAc–pentane). Then, the product was further hydrogeno-
lysed (1 atm) for 2 days in EtOH (20 mL) using Pd–C as cat-
alyst, in the presence of TFA (cat.). Filtration and removal of
2
-hydroxyaldehyde 12 is somewhat surprisingly about 50
times less efficient. Due to electronic effects it would not
be expected to be weaker as the carbonyl group is more elec-
trophilic, but perhaps steric hindrance or conformational
differences may be causing decrease in efficiency. The
acid 21 also showed some catalysis, which probably is
caused by a different mechanism, the nature of which, due
to the modest size of the effect, we will not speculate.
2
1
the solvents gave 8 (65 mg, 50%, two steps). [a]
+111 (c
.4, H O); IR (nmax): 3406, 2930, 1152, 1033, 951, 721,
D
0
7
2
ꢁ
1
1
07 cm ; H NMR (400 MHz, DMSO-d ): d 5.71 (m,
6
3. Conclusions
16H, OH), 5.02 (m, 6H, H-1), 4.04 (m, 3H), 3.77–2.89 (m,
3
CH3); C NMR (100 MHz, DMSO-d ): d 101.9, 101.8,
9H), 1.70 (m, 1H, CH–Me), 0.84 (d, 1H, J ¼6.0 Hz,
H,H
1
3
In summary, we have successfully prepared a series of
cup-shaped cyclodextrin derivatives with a considerable
variation of substituents on the bridge. A study of these com-
pounds as oxidation catalysts, a reaction where previously
reported cyclodextrin ketones have been found efficient,
6
101.2, 100.1, 83.1, 82.8, 81.5, 81.4, 80.6, 80.2, 74.2, 73.5,
72.9, 72.8, 72.7, 72.3, 72.2, 72.0, 71.6, 71.3, 71.2, 70.1,
68.4, 59.9, 59.7, 59.3. 34.5 (CH–CH ), 14.5 (CH ); MS calcd
3
3
for C H O Na: 1049.4, found: 1048.8.
40 66 30
(
a)
7
6
5
4
3
2
1
0
(b)
30
2
5
0
5
0
2
1
1
5
0
-10
10
-10
10
30
S (mM)
S (mM)
Figure 2. Kinetic plots for the oxidation of 2-hydroxyaniline into 2-aminophenoxazin-2-one catalysed by 19. (a) Hanes plot of S/Vcat vs S, where S is the con-
centration of 2-hydroxyaniline and Vcat is the catalysed rate of conversion. (b) A plot of Vcat vs S, which shows the hyperbolic relationship of the saturation
kinetics.

O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
8877
A
D
4
1
.1.2. 6 ,6 -Di-O-(prop-2-hydroxy-2-hydroxymethyl-
,3-dienyl)-hexadeca-O-benzyl-a-cyclodextrin (10). A
128.3, 128.2, 128.1, 128.0, 127.8, 127.6, 127.3, 127.2,
127.0, 1262.8, 127.7, 126.0 (CH ), 100.2, 100.1, 97.9,
97.8 (C-1), 82.6, 81.9, 81.1, 80.7, 80.6, 80.1, 80.0, 79.8,
78.9, 77.9, 77.7, 77.4, 76.5, 76.3, 76.2, 73.8, 73.7, 73.6,
73.5, 73.4, 73.3, 73.1, 73.0, 72.9, 72.6, 72.4, 72.3, 72.1,
72.0, 71.9, 70.9, 70.3, 69.9, 69.4, 69.2, 69.1; MS calcd for
Ar
A
D
mixture of 6 ,6 -di-O-(prop-2-methylidene-1,3-dienyl)-
hexadeca-O-benzyl-a-cyclodextrin (7) (5.0 g, 2.03 mmol),
NMO (0.82 g, 6.09 mmol), NaIO (1.30 g, 6.09 mmol) and
4
2
.5 wt% OsO (2.0 mL) in 10:1 acetone–H O (330 mL)
4 2
was kept stirring at room temperature overnight. The reac-
tion was quenched by addition of 10% Na S O (300 mL)
C152H160O Na: 2520.1, found: 2520.3.
32
2
2 3
A
D
and the product was extracted with EtOAc (3ꢀ100 mL).
4.1.4. 6 ,6 -Di-O-(prop-2-formyl-2-hydroxy-1,3-dienyl)-
a-cyclodextrin (12). Compound 11 (250 mg, 0.1 mmol)
was dissolved in 1:1 MeOH–EtOAc (20 mL). Then Pd–C
(200 mg) and TFA (cat.) were added and the mixture was
kept stirring overnight under hydrogen atmosphere. Filtra-
tion and removal of the solvents gave 12 as a foam (98 mg,
The combined organic fractions were dried over MgSO , fil-
4
tered and concentrated to dryness. The residue was purified
by column chromatography (pentane/1:2 EtOAc–pentane)
to afford title compound (4.40 g, 87%), as well as a small
A
D
amount of 6 ,6 -di-O-(prop-2-one-1,3-dienyl)-hexadeca-
O-benzyl-a-cyclodextrin (13, 216 mg, 4%).
2
3
1
93%). [a]D +98 (c 0.4, H O); H NMR (400 MHz, D O):
2
2
d 5.18, 5.07, 5.03 (m, 6H, H-1), 4.16 (m, 3H), 4.02–3.90
(m, 7H), 3.87–3.41 (m, 32H); C NMR (100 MHz,
2
3
13
[
a] +37 (c 1.1, CH Cl ,); IR (nmax): 3484, 3007, 3062,
2
D
2
3
1
d
029, 2922, 2869, 1605, 1496, 1453, 1353, 1208, 1092,
026, 909, 735, 697 cm ; H NMR (400 MHz, CDCl ):
7.21–6.90 (m, 80H, Ar–H), 5.49–5.44 (d, 4H,
DMSO-d ): d 102.4 102.0, 101.9, 101.4, 100.9, 100.6,
6
ꢁ
1 1
100.1 (C-1, C(OH)OC), 83.0, 82.9, 81.8, 81.7, 80.4, 76.6,
74.5, 74.4, 74.0, 73.8, 73.1, 72.9, 72.8, 73.6, 72.3, 72.2,
72.1, 71.6, 71.4, 71.3, 68.9, 68.6, 65.0, 62.0, 60.5, 60.1,
59.9, 59.5; MS calcd for C H O Na: 1079.3, found:
40 64 32
1079.6.
3
J1,2¼3.6 Hz, H-1, CH ), 5.16 (d, 2H, J ¼10.0 Hz, CH ),
2
H,H
2
4
.90 (d, 2H, J ¼10.4 Hz, CH ), 4.78–4.59 (dd, 12H,
H,H
2
J1,2¼4.0 Hz, J ¼12.0 Hz, H-1, CH ), 4.45–4.11 (m,
H,H
2
2
CH ), 3.58–3.55 (m, 5H), 3.41–3.20 (m, 12H), 2.99 (m,
3H), 4.05–3.74 (m, 16H), 3.65 (d, 2H, J ¼10.0 Hz,
H,H
A
D
4.1.5. 6 ,6 -Di-O-(prop-2-cyano-2-hydroxy-1,3-dienyl)-
hexadeca-O-benzyl-a-cyclodextrin (14). A mixture of
KCN (649 mg, 9.96 mmol) and NH Cl (802 mg, 15 mmol
2
1
3
2
H, JH,H¼12.8 Hz, CH ), 1.94 (br s, 2H, 2OH); C NMR
2
(
100 MHz, CDCl ): d 139.7, 139.4, 138.9, 138.5, 138.3,
3
4
1
1
1
8
7
7
38.0, 137.9 (Cipso), 128.4, 128.3, 128.2, 128.1, 128.0,
27.9, 127.8, 127.7, 127.6, 127.4, 127.2, 127.0, 126.6,
26.0 (CH ), 100.1, 100.0, 97.8 (C-1), 82.4, 82.2, 81.8,
1.2, 80.7, 80.6, 80.2, 79.2, 79.0, 78.9, 78.0, 77.7, 77.4,
6.3, 73.7, 73.6, 73.5, 73.2, 73.0, 72.9, 72.8, 72.4, 72.2,
2.0, 71.9, 71.5, 69.8, 69.5, 69.4, 69.2, 65.3 (CH); MS calcd
(14.99 mmol) in H O (10 mL) was added to a solution of
2
A
D
6 ,6 -di-O-(prop-2-oxo-1,3-dienyl)-hexadeca-O-benzyl-a-
cyclodextrin (13) (178 mg, 0.072 mmol) in a 1:1 mixture of
Ar
ꢂ
Et O–MeOH (10 mL) at 0 C. Reaction mixture was kept
2
stirring at room temperature for 40 h. Organic solvents
were removed in vacuo and the remaining water was ex-
tracted with CH Cl (4ꢀ20 mL). The combined organic
for C152H162O Na: 2522.1, found: 2522.1.
32
2
2
fractions were dried over MgSO , filtered and concentrated
4
A
D
4.1.3. 6 ,6 -Di-O-(prop-2-formyl-2-hydroxy-1,3-dienyl)-
hexadeca-O-benzyl-a-cyclodextrin (11). To a stirred solu-
tion of 6 ,6 -di-O-(prop-2-hydroxy-2-hydroxymethyl-1,
to dryness. The residue was purified by column chromato-
graphy (pentane/1:4 EtOAc–pentane) to afford the title
compound as a syrup (127 mg, 71%).
A
D
3
0
-dienyl)-hexadeca-O-benzyl-a-cyclodextrin (10) (120 mg,
.048 mmol) and Et N (0.1 mL, 0.72 mmol) in dry DMSO
2
5
[a] +35 (c 0.5, CH Cl ); IR (nmax): 3061, 3028, 2922,
D 2 2
3
(
0.8 mL) was dropwise added under N a solution of SO –
3
2869, 2250, 1496, 1453, 1353, 1207, 1094, 1058, 733,
696 cm ; H NMR (400 MHz, CDCl ): d 7.20–6.90 (m,
2
ꢁ1 1
Py complex (78 mg, 0.48 mmol) in dry DMSO (0.5 mL).
Reaction mixture was kept stirring at room temperature for
3
satd aq NaHCO3 (50 mL). Product was extracted with
CH Cl (50 mL), and the organic layer was separated and
3
80H, Ar–H), 5.46 (d, 1H, JH,H¼12.0 Hz, CH), 5.39 (d, 1H,
h, and after that time, it was quenched by addition of
J1,2¼4.0 Hz, H-1), 5.38 (d, 1H, J ¼4.0 Hz, H-1), 5.34 (d,
1,2
1H, J ¼4.0 Hz, H-1), 5.17 (d, 1H, J ¼4.0 Hz, H-1),
1,2
1,2
5.15 (d, 1H, J ¼4.0 Hz, H-1), 4.93 (d, 1H, J ¼12.0 Hz,
2
2
1,2
H,H
washed with brine (3ꢀ50 mL), H O (50 mL), dried over
CH), 5.86 (d, 1H, J ¼12.0 Hz, CH), 4.78–4.61 (m,
H,H
2
MgSO , filtered and the filtrate was concentrated to dryness
4
10H), 4.50–4.31 (m, 12H), 4.27–4.13 (m, 8H), 4.10–3.65
(m, 23H), 3.59–3.14 (m, 16H), 3.02 (d, 2H, J ¼8.0 Hz,
H.H
and purified by column chromatography (pentane/1:3
EtOAc–pentane) to afford 11 as a syrup (116 mg, 97%).
1
3
CH); C NMR (100 MHz, CDCl ): d 139.8, 139.7, 139.5,
3
1
39.4, 139.3, 138.9, 138.5, 138.4, 138.1, 137.9, 137.7
2
3
[
3
1
a] +28 (c 0.5, CH Cl ); IR (nmax): 3435, 3006, 3062,
2
(Cipso), 128.6, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9,
127.8, 127.6, 127.4, 127.2, 127.1, 127.0, 126.9, 126.7,
126.1, 126.0 (CH ), 119.0 (CN), 100.4, 100.3, 100.2,
D
2
028, 2923, 2867, 1736, 1496, 1453, 1353, 1208, 1093,
027, 909, 756, 733, 696, 622 cm ; H NMR (400 MHz,
ꢁ1 1
Ar
CDCl ): d 9.22 (s, 1H, CHO), 7.21–6.92 (m, 80H, Ar–H),
3
97.9, 97.7 (C-1), 82.8, 82.6, 82.4, 81.4, 81.1, 81.0, 80.7,
80.4, 80.1, 80.0, 79.8, 78.8, 78.7, 77.9, 77.3, 76.3, 76.1,
74.0, 73.8, 73.6, 73.5, 73.4, 73.2, 73.0, 72.8, 72.5, 72.4,
72.2, 72.0, 71.8, 70.6, 70.0, 69.9, 69.5, 69.2, 68.9, 60.6;
5
.45 (2d, 2H, JH,H¼10.4 Hz, 2CH), 5.38 (d, 1H,
J1,2¼4.0 Hz, H-1), 5.36 (d, 1H, J ¼4.0 Hz, H-1), 5.17
1,2
(
2d, 2H, J ¼10.4 Hz, 2CH), 4.90 (2d, 2H, J ¼10.2 Hz,
H,H
H,H
2
CH), 4.76–4.57 (m, 12H), 4.45–4.11 (m, 21H), 4.02–4.44
MS calcd for C152H159NO Na: 2517.1, found: 2517.1.
31
(
2
m, 26H), 3.33–3.22 (m, 9H), 3.06 (d, 2H, JH,H¼10.0 Hz,
1
3
A
D
CH), 3.01 (d, 2H, JH,H¼9.6 Hz, 2CH);
C NMR
4.1.6. 6 ,6 -Di-O-(prop-2-aminomethyl-2-hydroxy-1,3-
dienyl)-a-cyclodextrin (15). Compound 14 (0.14 g,
0.05 mmol) was dissolved in 1:1 MeOH–EtOAc (4 mL).
(
100 MHz, CDCl ): d 201.0 (CO), 139.8, 139.5, 139.4,
3
1
39.0, 138.5, 138.4, 128.2, 138.0, 137.9 (Cipso), 128.4,

8878
O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
Then Pd–C (88 mg) and TFA (cat.) were added and the mix-
ture was kept stirring overnight under hydrogen atmosphere.
Filtration and removal of the solvents gave 15 as a foam
70.1, 69.5, 68.4, 41.9 (CH–CH OH); MS calcd for
2
C H O Na: 1065.3, found: 1064.5.
4
0
66 31
1
A
D
(
50 mg, quant). H NMR (400 MHz, D O): d 5.05–4.94
2
4.1.9. 6 ,6 -Di-O-(prop-2-formyl-1,3-dienyl)-hexadeca-
A
D
(
m, 6H, H-1), 4.11–4.05 (m, 2H), 4.00–3.66 (m, 23H),
O-benzyl-a-cyclodextrin (18). To a solution of 6 ,6 -
di-O-(prop-2-hydroxymethylidene-1,3-dienyl)-hexadeca-O-
benzyl-a-cyclodextrin (16) (857 mg, 0.34 mmol) in CH Cl
2
3
3
1
8
7
.58–3.48 (m, 12H), 3.46–3.35 (m, 4H), 3.30 (m, 2H),
.11 (m, 1H); C NMR (100 MHz, D O): d 101.6, 100.9,
00.7, 100.5 (C-1), 82.2, 82.0, 81.9, 81.7, 81.5, 81.1, 81.0,
0.7, 74.3, 74.1, 73.5, 73.3, 72.7, 72.5, 72.3, 72.2, 72.1,
2.0, 71.9, 71.8, 7.3, 71.0, 69.7, 69.0, 53.3, 43.3, 43.0; MS
1
3
2
2
(30 mL) was added Dess–Martin periodinane (440 mg,
1.04 mmol) and the corresponding mixture was kept stirring
at room temperature for 4 h. Reaction was quenched by ad-
dition of Et O (50 mL) and a mixture of satd aq NaHCO –
calcd for C H NO Na: 1080.0, found: 1080.4.
4
0
67
31
2
3
5
% Na S O (75 mL) and the biphasic mixture was kept
2 2 3
A
D
4
hexadeca-O-benzyl-a-cyclodextrin (16). solution
.1.7. 6 ,6 -Di-O-(prop-2-hydroxymethyl-1,3-dienyl)-
A
stirring at room temperature for further 2 h. The organic
layer was then separated, dried over Na SO , filtered and
the filtrate was concentrated to dryness and purified by
column chromatography (1:5 EtOAc–pentane/1:3.5
EtOAc–pentane) to afford pure 18 as a white foam
(536 mg, 65%).
2
4
A
D
of 6 ,6 -di-O-(prop-2-methylidene-1,3-dienyl)-hexadeca-
O-benzyl-a-cyclodextrin (2.00 g, 0.81 mmol) in dry THF
(
(
20 mL) was added to a 0.5 M solution of 9-BBN in THF
27 mL) and the mixture was kept stirring under nitrogen
overnight. Then reaction mixture was cooled down to 0 C
and a 3 M solution of NaOH (6.5 mL) and 35% H O
ꢂ
2
5
[a] +46 (c 0.8, CH Cl ); IR (nmax): 3061, 3028, 2922,
2
2
2
D
2
were slowly added and the corresponding mixture was
kept stirring at room temperature overnight. Then, CH Cl
2869, 1726, 1604, 1495, 1452, 1352, 1207, 1093, 1027,
734, 696 cm ; H NMR (400 MHz, CDCl ): d 9.24 (br s,
ꢁ1 1
2
2
3
(
150 mL) was added and the organic layer was washed
1H, CHO), 7.22–6.91 (m, 80H, Ar–H), 5.45–5.44 (m, 4H,
CH , H-1), 5.19–5.13 (d, 3H, J ¼11.4 Hz, CH), 4.89–
with satd aq NH Cl (3ꢀ50 mL), satd aq NaCl (1ꢀ50 mL),
4
2
H,H
dried over MgSO , filtered and the filtrate was concentrated
4
4.86 (m, 3H), 4.78–4.59 (m, 10H), 4.49–3.74 (m, 37H),
3.62–3.12 (m, 21H), 2.08 (m, 1H, CH); C NMR
(100 MHz, CDCl ): d 200.9 (CO), 139.8, 139.5, 139.4,
13
to dryness. The residue was purified by flash chromato-
graphy (pentane/1:2 EtOAc–pentane) to give compound
1
(
1
d
3
2
5
6 as a syrup (1.63 g, 81%). [a]D +42 (c 0.5, CH Cl ); IR
2
138.9, 138.6, 138.4, 138.0, 137.9 (Cipso), 129.1, 128.5,
128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7,
127.6, 127.4, 127.3, 127.2, 127.0, 126.7, 126.6, 126.0
2
nmax): 3062, 3028, 2922, 2868, 1495, 1453, 1353, 1207,
ꢁ
1 1
092, 1027, 734, 696 cm ; H NMR (400 MHz, CDCl ):
3
7.24–6.91 (m, 80H, Ar–H), 5.50–5.43 (d, 4H,
(CH ), 100.0, 99.8, 99.7, 98.3, 97.7 (C-1), 82.9, 84.4,
Ar
JH,H¼10.0 Hz, CH , H-1), 5.19–5,14 (d, 2H, J ¼9.4 Hz,
82.2, 81.7, 81.5, 81.4, 81.1, 81.0, 80.7, 80.3, 79.9, 79.7,
79.4, 79.3, 77.8, 76.5, 76.3, 73.7, 73.6, 73.5, 73.1, 73.0,
72.5, 72.4, 72.2, 72.1, 72.0, 71.9, 71.6, 70.2, 69.7, 69.4,
69.3, 69.2, 69.1, 65.9, 65.6, 52.63 (CH); MS calcd for
2
H,H
CH ), 4.90 (d, 2H, J ¼9.6 Hz, CH ), 4.77–4.59 (d, 12H,
2
H,H
2
JH,H¼10.0 Hz, CH , H-1), 4.42–4.12 (m, 26 H), 4.04–3.74
2
(
m, 15H), 3.59 (d, 2H, J ¼9.6 Hz, 2CH), 3.52 (dd, 2H,
H,H
J¼4.0 Hz, J¼10.0 Hz), 3.46 (d, 2H, J¼11.2 Hz), 3.39–
C152H160O Na: 2504.1, found: 2504.4.
31
3
.22 (m, 11H), 3.01 (m, 2H), 1.70–1.43 (m, 2H, CH, OH);
C NMR (100 MHz, CDCl ): d 139.8, 139.5, 139.0,
1
3
A
D
4.1.10. 6 ,6 -Di-O-(prop-2-formyl-1,3-dienyl)-a-cyclo-
dextrin (19). Compound 18 (0.48 g, 0.19 mmol) was
dissolved in 1:1 MeOH–EtOAc (20 mL). Then Pd–C
(345 mg) and TFA (cat.) were added and the mixture was
kept stirring overnight under hydrogen atmosphere. Filtra-
tion and removal of the solvents gave 19 as a foam
3
1
1
1
1
8
7
6
38.9, 138.6, 138.4, 138.3, 138.0, 137.9 (Cipso), 128.5,
28.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7,
27.6, 127.5, 127.4, 127.2, 127.0, 126.7, 126.0 (CHAr),
00.0, 99.8, 99.7, 98.1, 97.7 (C-1), 82.4, 82.3, 81.6, 81.2,
0.8, 80.3, 80.2, 79.7, 79.1, 79.0, 77.9, 76.3, 73.6, 73.5,
3.4, 73.2, 73.0, 72.4, 72.2, 72.0, 71.9, 70.0, 69.7, 69.6,
2
5
1
(0.18 g, 90%). [a]D +104 (c 0.6, H O); H NMR
2
A–F
9.2, 68.9, 63.7 (CH OH), 41.7 (CH); Anal. Calcd for
2
(400 MHz, D O): d 5.18–5.15, 5.09–5.08 (m, 6H, H-1 ),
2
4.03–3.59 (m, 36H, H-2–H6 ), 3.39 (m, 4H, 2CH ). 2.85
2
A–F
C152H162O : C 73.47, H 6.57. Found: C 73.30, H 6.59.
31
MS calcd for C152H162O Na: 2506.1, found: 2506.3.
31
1
3
(m, 1H, CH–CHO); C NMR (100 MHz, DMSO-d6):
d 102.0, 101.8, 101.3, 101.2, 100.7, 100.3 (C-1), 834.0,
82.7, 82.4, 82.3, 82.0, 81.8, 81.6, 81.4, 80.5, 73.9, 73.8,
73.5, 72.7, 72.0, 71.7, 71.4, 70.7, 66.5, 66.3, 66.2, 66.1,
60.6, 60.1, 59.5, 59.2, 59.0 52.9 (CH–CHO); MS calcd for
C H O Na: 1063.3, found: 1062.9.
A
D
4
.1.8. 6 ,6 -Di-O-(prop-2-hydroxymethyl-1,3-dienyl)-
a-cyclodextrin (17). Compound 16 (0.60 g, 0.24 mmol)
was dissolved in 1:1 MeOH–EtOAc (20 mL). Then Pd–C
(241 mg) and TFA (cat.) were added and the mixture was
kept stirring overnight under hydrogen atmosphere. Filtra-
4
0
64 31
A
D
tion and removal of the solvents gave 17 as a foam
(
4.1.11. 6 ,6 -Di-O-(prop-2-carboxy-1,3-dienyl)-hexa-
deca-O-benzyl-a-cyclodextrin (20). A solution of 6 ,
2
5
A
0.21 g, 83%). [a]D +103 (c 0.6, H O); IR (nmax): 3445,
2
ꢁ1
1
D
2
931, 1411, 1028, 951, 708 cm ; H NMR (400 MHz,
6 -di-O-(prop-2-hydroxymethylidene-1,3-dienyl)-hexadeca-
O-benzyl-a-cyclodextrin 16 (0.79 g, 0.32 mmol) and Dess–
D O): d 5.13 (d, 1H, J ¼4.0 Hz, H-1), 5.12 (d, 1H,
2
1,2
J1,2¼3.6 Hz, H-1), 5.04–5.00 (m, 4H, H-1), 4.17 (m, 3H),
Martin periodinane reagent (0.40 g, 0.95 mmol) in CH Cl
2
2
4
.10–3.59 (m, 35H), 3.42–3.31 (m, 3H), 3.25 (t, 1H,
(35 mL) was kept at room temperature overnight and then
quenched by addition of Et O (100 mL) and a satd aq
1
3
J¼9.2 Hz), 1.96 (m, 1H, CH–CH OH);
C NMR
100 MHz, D O): d 101.6 (2C, C-1), 101.0 (2C, C-1),
2
2
(
NaHCO containing 5% of Na S O (75 mL) and kept stir-
2 2 3
2
3
1
7
00.3, 100.1 (C-1), 82.0, 81.5, 81.4, 80.3, 80.1, 74.1, 72.7,
2.6, 72.4, 72.3, 72.2, 72.1, 71.9, 71.8, 71.4, 71.2, 70.9,
ring at room temperature for 2 h. Then, the organic layer
was separated, dried over MgSO4 and concentrated to

O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
8879
dryness. To a solution of the residue in 2-methylbut-2-ene
(8 mL), BuOH (21 mL) and THF (9 mL) was added a solu-
tion of NaClO (0.65 g, 7.2 mmol) and NaH PO (0.60 g,
5.43 (dd, 4H, J1,2¼3.6 Hz, J ¼10.8 Hz, H-1, CH), 5.18
H,H
t
(d, 1H, JH,H¼9.8 Hz, CH), 5.15 (d, 1H, J ¼9.8 Hz, CH),
H,H
4.89 (d, 1H, J ¼10.0 Hz, CH), 4.88 (d, 1H, J ¼10.4 Hz,
2
2
4
H,H
H,H
5
.0 mmol) in water (5 mL) and the corresponding mixture
CH), 4.77–4.59 (m, 12 H), 4.52–4.15 (m, 22H), 4.12–3.72
(m, 18 H), 3.66–3.18 (m, 18H), 3.51 (s, 3H, OMe), 2.38
(m, 1H, CH); C NMR (100 MHz, CHCl ): d 171.9 (CO),
was kept stirring at room temperature overnight. The reac-
tion was quenched by addition of 1 M HCl (24 mL) and
the product was extracted with EtOAc (3ꢀ50 mL). The or-
1
3
3
139.8, 139.4, 138.9, 138.8, 138.6, 138.l4, 138.3, 138.2,
138.0, 137.8 (Cipso), 128.7, 128.6, 128.5, 128.4, 128.3,
128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.5, 127.2,
ganic phase was dried over MgSO , filtered and the filtrate
4
was concentrated to dryness and purified by flash chromato-
graphy (1:4 EtOAc–pentane/1:2 EtOAc–pentane contain-
ing 1% HCOOH) to give compound 20 as a syrup (0.45 g,
126.8, 126.3 (CH ), 100.0, 99.9, 99.7, 99.6, 98.1, 97.6 (C-1),
Ar
82.1, 82.0, 81.7, 81.3, 81.2, 81.1, 80.8, 80.7, 80.3, 79.9,
79.6, 79.4, 79.1, 78.9, 77.9, 77.8, 76.8, 76.3, 73.7, 73.5,
73.4, 73.1, 72.9, 72.4, 72.3, 72.2, 72.0, 71.5, 69.9, 69.6,
69.5, 69.4, 69.1, 68.9, 67.8, 67.0, 51.7 (OMe), 45.6 (CH);
2
5
5
3
6
8
6%, two steps). [a]D +41 (c 0.5, CH Cl ); IR (nmax):
2 2
061, 3028, 2923, 1774, 1495, 1452, 1352, 1027, 734,
96 cm ; H NMR (400 MHz, CDCl ): d 7.20–6.91 (m,
ꢁ
1 1
3
0H, Ar–H), 5.48–5.41 (d, 4H, JH,H¼10.0 Hz, CH), 5.16
MS calcd for C153H162O Na: 2534.1, found: 2533.8.
32
(
d, 1H, JH,H¼10.0 Hz, CH), 5.14 (d, 1H, J ¼10.0 Hz,
H,H
A
D
CH) 4.88 (d, 1H, J ¼10.4 Hz, CH), 4.77–4.58 (m, 13H),
4.1.14. 6 ,6 -Di-O-(prop-2-methoxycarbonyl-1,3-
dienyl)-a-cyclodextrin (23). Compound 22 (0.52 g,
0.21 mmol) was dissolved in 1:1 MeOH–EtOAc (50 mL).
H,H
4
1
.45–4.12 (m, 21H), 4.07–3.73 (m, 17H), 3.62–3.17 (m,
9H), 2.38 (m, 1H, CH); C NMR (100 MHz, CDCl3):
1
3
d 175.8 (CO), 139.7, 139.4, 138.9, 138.7, 138.8, 138.5,
Then Pd(OH) (150 mg) and TFA (cat.) were added and
2
1
1
1
9
8
7
7
6
2
38.3, 138.2, 138.1, 137.9, 137.8 (Cipso), 128.4, 128.3,
28.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5,
27.4, 127.3, 126.9, 126.6, 126.5, 126.0 (C ), 99.9, 99.8,
9.7, 99.6, 98.1, 97.6 (C-1), 82.1, 82.0, 81.7, 81.3, 81.2,
1.0, 80.7, 80.3, 79.9, 79.5, 79.3, 79.0, 78.9, 77.8, 77.4,
6.7, 76.2, 73.6, 73.5, 73.4, 73.2, 72.9, 72.3, 72.2, 72.0,
1.9, 71.5, 69.8, 69.5, 69.4, 69.3, 69.0. 68.9, 68.5, 67.3,
the mixture was kept stirring overnight under hydrogen
atmosphere. Filtration and removal of the solvents gave 23
2
5
as a foam (0.22 g, quant). [a]D +98 (c 0.7, H O); IR
2
Ar
ꢁ
1
1
(nmax): 3366, 2928, 1728, 1677, 950 cm
;
H NMR
(400 MHz, DMSO-d ): d 5.89–5.0 (m, 11H, OH), 4.88,
6
4.78–4.76 (m, 6H, H-1), 4.64–4.10 (m, 5H, OH), 3.96–
3.89 (m, 4H), 3.81–3.23 (m, 34H), 3.61 (s, 3H; OMe),
3.07–3.01 (m, 2H), 2.63 (m, 1H); C NMR (100 MHz,
1
3
6.5, 45.6 (CH–COOH); MS calcd for C152H160O Na:
32
520.1, found: 2520.1.
DMSO-d ): d 172.2 (CO), 102.1, 101.9, 101.4, 101.2,
6
1
00.6, 100.2 (C-1), 83.0, 82.9, 81.8, 81.3, 81.2, 80.3, 74.5,
A
D
4
.1.12. 6 ,6 -Di-O-(prop-2-carboxy-1,3-dienyl)-a-cyclo-
74.4, 74.5, 74.4, 73.0, 72.8, 72.4, 72.2, 72.0, 71.6, 71.4,
71.3, 71.2, 70.1, 69.1, 68.4, 67.8, 60.3, 59.8, 59.5, 59.4,
59.2, 51.6 (OMe), 46.5 (CH); MS calcd for C H O Na:
dextrin (21). Compound 20 (0.43 g, 0.17 mmol) was dissol-
ved in 1:1 MeOH–EtOAc (60 mL). Then Pd–C (144 mg) and
TFA (cat.) were added and the mixture was kept stirring
overnight under hydrogen atmosphere. Filtration and re-
moval of the solvents gave 21 as a foam (0.16 g, 90%).
a] +109 (c 0.4, H O); IR (nmax): 3376, 2929, 1724,
D 2
1374, 1037, 950, 708 cm ; H NMR (400 MHz, D O):
d 5.13–4.99 (m, 6H, H-1 , 4.19–3.59 (m, 36H, H-2–
H6 ), 3.35 (m, 4H, 2CH ), 2.84 (m, 1H, CH–COOH);
2
C NMR (100 MHz, D O): d 175.7 (COOH), 101.7,
2
01.5, 101.1, 101.0, 100.0 (C-1), 82.0, 81.8, 81.4, 81.0,
0.3, 80.0, 74.3, 74.2, 72.7, 72.5, 72.4, 72.3, 72.0, 71.9,
1.8, 71.7, 71.6, 71.2, 70.8, 70.0, 69.4, 68.1. 60.8, 60.6,
4
1 66 32
1093.3, found: 1092.7.
4.2. Procedure for determining the rate of oxidation
2
5
[
ꢁ
1
1
Each assay was performed on 8–16 samples (2 mL each) of
the appropriate substrate at different concentrations in 0.1 M
phosphate buffer. To each sample was added 1 mg of the cor-
responding cyclodextrin or nothing (as control) and 64 mM
2
A–F
A–F
1
3
ꢂ
1
8
7
6
H O . The reactions were followed at 25 C using UV ab-
2
2
sorption at 400 nm and typically monitored for 3 h. Veloci-
ties were determined as the slope of the progress curve of
each reaction. Uncatalysed velocities were obtained directly
from the control samples. Catalysed velocities were calcu-
lated by subtracting the uncatalysed rate from the total rate
of the appropriate cyclodextrin containing sample. The cat-
alysed velocities were used to construct Hanes plots ([S]/V
vs [S]) to ensure that the reaction followed Michaelis–
A–F
0.1 (C2–C6 ), 46.6 (CH–COOH); MS calcd for
C H O Na: 1079.3, found: 1078.5.
4
0
64 32
A
D
4.1.13. 6 ,6 -Di-O-(prop-2-methoxycarbonyl-1,3-di-
enyl)-hexadeca-O-benzyl-a-cyclodextrin (22). A solution
A
D
of 6 ,6 -di-O-(prop-2-carboxylic acid-1,3-dienyl)-hexa-
deca-O-benzyl-a-cyclodextrin (20) (0.8 g, 0.32 mmol) in
SOCl was kept at room temperature for 1 h. Then SOCl
Menten kinetics. In that case K and V
m
using least square non-linear regression fitting to the Vmax vs
S curve. kcat was calculated as Vmax/[cyclodextrin]. kuncat was
were determined
max
2
2
was removed under reduced pressure and the residue was
dissolved in CH Cl (4 mL). Triethylamine (0.1 mL) was
determined as the slope from a plot of V
ꢂ
vs [S]. The
2
2
uncat
ꢂ
added and the solution was cooled down to 0 C, when
MeOH (4 mL) was added dropwise. After warming up to
room temperature, the solution was kept at that temperature
for 3 h. Removal of the solvents and column chromato-
graphy (pentane/1:3 EtOAc–pentane) afforded 22 as
following extinction coefficients (25 C, pH 7) and wave-
lengths were determined and used: 3-aminophenoxaz-
2-one, 0.42 mM cm at 400 nm.
ꢁ1
ꢁ1
Acknowledgements
2
5
a white foam (0.72 g, 89%). [a]D +42 (c 0.6, CH Cl ); IR
(
2
2
nmax): 3062, 3028, 2922, 2869, 1739, 1605, 1496, 1453,
;
We acknowledge the Danish National Science Research
Council (SNF) and the Lundbeck foundation for financial
support.
ꢁ1
1
1
(
352, 1039, 1027, 909, 755, 696 cm
H NMR
400 MHz, CHCl ): d 7.23–6.89 (m, 80H, Ar–H), 5.50–
3

8880
O. L. Lopez et al. / Tetrahedron 63 (2007) 8872–8880
16. Takahashi, Y.; Ogawa, T. Carbohydr. Res. 1987, 164,
References and notes
2
7. Sato, T.; Nakamura, H.; Ohno, Y. Carbohydr. Res. 1990, 199,
77–296.
1
1
1
2
1
2
3
4
5
6
. Breslow, R.; Dong, S. D. Chem. Rev. 1998, 98, 1997–2011.
. D’Souza,V. T.;Bender, M. L.Acc.Chem. Res. 1987, 20, 146–152.
. Tabushi, I. Acc. Chem. Res. 1982, 15, 66–72.
. Hedges, A. R. Chem. Rev. 1998, 98, 2035–2044.
. Szejtli, J. Chem. Rev. 1998, 98, 1743–1753.
. Tabushi, I.; Kuroda, Y.; Yokota, K.; Yuan, L. C. J. Am. Chem.
Soc. 1981, 103, 1–6.
. Khan, A. R.; Forgo, P.; Stine, K. J.; D’Souza, V. T. Chem. Rev.
3
1–35.
8. Lecourt, T.; Herault, A. J.; Pearce, M.; Sollogoub, M.; Sina €y , P.
Chem.—Eur. J 2004, 10, 2960–2971.
9. Pearce, A. J.; Sina €y , P. Angew. Chem., Int. Ed. 2000, 39,
3
0. Rousseau, C.; Ortega-Caballero, F.; Nordstrøm, L. U.;
610–3612.
Christensen, B.; Petersen, T. E.; Bols, M. Chem.—Eur. J
2
7
8
9
005, 11, 5094–5101.
1
998, 98, 1977–1996.
. Engeldinger, E.; Armspach, D.; Matt, D. Chem. Rev. 2003, 103,
147–4173.
. Wang, W.; Pearce, A. J.; Zhang, Y.; Sina €y , P. Tetrahedron:
Asymmetry 2001, 12, 517–523.
2
2
2
2
2
2
2
2
1. Isobe, M.; Ichikawa, Y.; Bai, D.-L.; Masaki, H.; Goto, T.
Tetrahedron 1987, 43, 4767–4776.
2. Cossy, J.; Bauer, D.; Bellosta, V. Tetrahedron 2002, 58, 5909–
4
5
922.
3. Waddell, S. T.; Eckert, J. M.; Blizzard, T. A. Heterocycles
996, 43, 2325–2332.
4. Zhang, Y. L.; Shing, T. K. M. J. Org. Chem. 1997, 62, 2622–
624.
5. Phukan, P.; Sasmal, S.; Maier, M. E. Eur. J. Org. Chem. 2003,
733–1740.
1
1
1
1
1
1
0. Rousseau, C.; Nielsen, N.; Bols, M. Tetrahedron Lett. 2004, 45,
709–8711.
1. Ortega-Caballero, F.; Bjerre, J.; Laustsen, L. S.; Bols, M.
J. Org. Chem. 2005, 70, 7217–7226.
2. Rousseau, C.; Christensen, B.; Petersen, T. E.; Bols, M. Org.
Biomol. Chem. 2004, 2, 3476–3482.
3. Rousseau, C.; Christensen, B.; Bols, M. Eur. J. Org. Chem.
1
8
2
1
6. Dias, L. C.; Ba ꢀu , R. Z.; de Sousa, M. A.; Zukerman-Schpector,
J. Org. Lett. 2002, 4, 4325–4327.
7. Day, B. W.; Kangani, C. O.; Avor, K. S. Tetrahedron:
Asymmetry 2002, 13, 1161–1166.
8. Clausen, M. H.; Jørgensen, M. R.; Thorsen, J.; Madsen, R.
J. Chem. Soc., Perkin Trans. 1 2001, 543–551.
2005, 2734–2739.
4. Marinescu, L.; Molbach, M.; Rousseau, C.; Bols, M. J. Am.
Chem. Soc. 2005, 127, 17578–17579.
5. Marinescu, L. G.; Bols, M. Angew. Chem., Int. Ed. 2006, 45,
4590–4593.