1-(4-Nitrophenoxycarbonyl)-7-pyridin-4-yl indolizine: A new versatile fluorescent building block. Application to the synthesis of a series of fluorescent β-cyclodextrins

Article abstract of DOI:10.1016/j.tet.2005.02.063

The synthesis of a series of new fluorescent building blocks 1a-d incorporating a pyridinoindolizine unit and two potentially reactive sites is described. The reaction of 1a-d with the mono-6-amino-6-deoxy-β- cyclodextrin provides the corresponding fluorescent water soluble hosts 2a-d in good yield. The sensor properties of 2a-d in the presence of 1-adamantanol is described.

Full text of DOI:10.1016/j.tet.2005.02.063

Tetrahedron 61 (2005) 3939–3945
1-(4-Nitrophenoxycarbonyl)-7-pyridin-4-yl indolizine:
a new versatile fluorescent building block. Application to the
synthesis of a series of fluorescent b-cyclodextrins
*
Franc¸ois Delattre, Patrice Woisel, Gheorghe Surpateanu, Francine Cazier and Philippe Blach
` ´ ˆ
Laboratoire de Synthese Organique et Environnement, EA2599, Universite du Littoral Cote d’Opale, 145, avenue Maurice Schumann,
59140 Dunkerque, France
Received 17 November 2004; revised 11 February 2005; accepted 22 February 2005
Abstract—The synthesis of a series of new fluorescent building blocks 1a–d incorporating a pyridinoindolizine unit and two potentially
reactive sites is described. The reaction of 1a–d with the mono-6-amino-6-deoxy-b-cyclodextrin provides the corresponding fluorescent
water soluble hosts 2a–d in good yield. The sensor properties of 2a–d in the presence of 1-adamantanol is described.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
but also antioxidant properties.12 In addition to exhibiting a
spectrum of pharmacological effects, synthetic indolizinic
derivatives are also well known for their fluorescence
properties and some of them have already been used as
dyes13 and biological markers.14
Designing functionalisable fluorescent organic compounds
which can be used as building blocks for the synthesis of
new chromogenic derivatives with distinctly different
physical and/or chemical properties is a great interest to
biologists1 and organic materials chemists.2 Such reactive
fluorophores are, for example, widely employed as
fluorescent labels in the study of complex biological
systems (DNA hybridisation)3 and in analytical HPLC
derivatisation reactions4 in order to overcome the problem
of low detection limits. It has been shown that the presence
of a functionality on the fluorescent backbone could also
offer the opportunity to modify their solubility by introdu-
cing long chain or ionic moieties with the aim to improving
the solubility in organic solvents and water, respectively.5
Considering the well known fluorescence properties of
indolizine derivatives, the incessant need for new reactive
fluorophores and the increasing importance of fluorescence
spectroscopy in both biological and supramolecular recog-
nition fields, we were interested on the synthesis on new
fluorescent building blocks including an indolizinic unit
bearing two potential different reactive functions, e.a a
4-nitrophenoxycarbonyl leaving group (site A) and a free
pyridinic moiety (site B), as sites for further structural
modifications (Fig. 1).
Herein, we describe the convenient synthesis and the
characterisation of the new type fluorescent building block
1 and its successful incorporation into the primary face of
the b-cyclodextrin through the reactivity of the nitrophenyl-
ester group (site A). Fluorescence properties of graft
compounds 2a–d are also described through, notably, the
evaluation of their sensitivity factors in the presence of
1-adamantanol.
The attachment of fluorophores to synthetic receptors has
also received considerable interest over the last few years, in
endeavours to furnish new fluorescent sensors.6 In particu-
lar, fluorescent cyclodextrins have generated considerable
interest from the synthetic community as witnessed by
recent articles dealing with their synthesis and emphasizing
their sensory,7 but also their biochemical8 and photoelec-
tronic9 properties. On the other hand, indolizinic derivatives
are of interest as biologically active products and are well
known to exhibit a variety of pharmacological effects
including cardiovascular,10 anti-inflammatory activities11
2. Results and discussion
2.1. Synthesis and characterisation
Keywords: b-Cyclodextrins; Fluorophores; Indolizinic derivatives.
*
Corresponding author. Tel.: C33 32865 8246; fax: C33 32865 8260;
e-mail: woisel@univ-littoral.fr
Scheme 1 displays the strategy involved for the preparation
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.02.063

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F. Delattre et al. / Tetrahedron 61 (2005) 3939–3945
Figure 1. The new fluorescent building block 1 and its corresponding b-cyclodextrin fluorescent sensor 2.
Scheme 1. Synthesis of 1a–e.
of the new reactive fluorophore 1. The literature offers
several methods for the construction of the indolizinic
unit.15 Among them, due to the easy access of 1,3 dipoles
derived from cycloimmonium salts and the wide range of
dipolarophiles commercially available, the 1,3-dipolar
cycloaddition of pyridinium ylide derivatives with activated
double or triple bonds has been shown to be a highly
effective and powerful strategy to build this pentatomic
framework.16
electron-deficient compound 7 to give primary cycloadducts
8a–d which spontaneously furnish, after rearomatisation,
finals compounds 1a–d, in good yields (Table 1). It should
be noted, that, to the best of our knowledge, the
dipolarophile 7 was used for the first time in this type of
chemical transformation. Moreover the presence of the
leaving group (4-NO2PhO–) in its structure does not affect
the yield compared to other dipolarophiles previously
used.16b,k Thus, this activated dipolarophile could offer
various applications with the aim to functionalising other
heterocyclic frameworks. The structure of 1a–d were
deduced from their spectroscopic data. IR spectra of 1a–d
showed three characteristic absorption bands at z1610,
1725, 1520 cmK1 ascribed to n (C]O), n (O–C]O) and n
(NO2), respectively. The C13 spectra exhibited two signals
z185 and 160 ppm for 1a–d, which confirm the presence of
a ketone and a carboxylic acid derivative, respectively.
Examination of the crude reaction mixture by 400 MHz 1H
Thus, the salt method17 has been applied in order to obtain
the bipyridinium ylides 6. Quaternization of the bipyridine 3
at room temperature in dry acetone with the commercially
available 4-substituted u-bromoacetophenones 4a–d gave
the corresponding monosalts 5a–d in high yields. Next these
salts in the presence of triethylamine (TEA) form the
monosusbstituted carbanions ylides 6a–d ‘in situ’ which
undergo a 1,3-dipolar cycloaddition reaction with the

F. Delattre et al. / Tetrahedron 61 (2005) 3939–3945
3941
Table 1. Emission variations of 2a–d, measured in phosphate buffer (pHZ7.0, 25 8C) with [2a–d]0Z0.01 mM and [1-adamantanol]Z0.1 mM
Compound
Yield (%)
DI/I0
lexc (nm)
Kb (MK1
)
1a
1b
1c
1d
2a
2b
2c
2d
49
53
57
46
52
54
58
38
—
—
—
—
0.449
0.306
0.094
0.321
—
—
—
—
274
273
275
276
—
—
—
—
79,500
91,200
192,000
127,600
NMR spectroscopy revealed the formation of 1a–d as a
single regioisomer. The assignments of most of the proton
signals were performed using 1D NMR experiment (see
Section 4) and the complete structure elucidation, including
the determination of the relative regiochemistry, were
secured through two-dimensional techniques (COSY-LR
and NOE). The absence in the COSY-LR spectra and in
NOESY experiments of crossed signals between H05 and
H06 allowed the unambiguous assignment of the regio-
chemistry of 1a–d.
compounds 2a–d. All Roesy spectra do not display NOE
cross peaks between the H-3 and H-5 protons of
thecyclodextrin part and aromatics protons of the pyridino-
indolizinic moiety, which indicate distinctly that the
fluorophore arm is located outside the cavity. In a previous
paper,21 we described for the first time the reactivity of
cycloimmonium ylides with the electroactive propinamido-
bCD. This new tool for the functionalisation of the primary
face of the b-cyclodextrin has resulted in the synthesis of
2a–d. Here, the new proposed method offers two major
advantages, as it furnish significant higher yields (20–30%
higher) and because it offers the possibility to graft directly
this new fluorescent arm into another molecular scaffolds
with the aim to obtain new fluorescent artificial receptors.
The mono-6-amino-6-deoxy-b-cylodextrin 9 was synthe-
sised via a three step process involving a preliminary
regioselective tosylation into the primary face of bCD,18
following, by the displacement of the tosyl leaving group
19
with NaN3 and the reduction of the azido group via the
2.2. Fluorescence study
Stau¨dinger reaction.20 (Scheme 2) Then, the mono-6-
amino-6-deoxy-b-cylodextrin 9 was treated with 1a–d in
NMP (N-Methylpyrrolidone) at 50 8C to give the corre-
sponding fluorescent b-CD. Crude 2a–d were isolated by
precipitation from acetone and then successively purified
using Sephadex CM25 and G15 chromatography, respect-
ively. Analysis of 2a–d by FTIR, NMR, ESIMS and
elemental analysis are in agreement with the proposed
structures and with the literature data. The NMR spectra of
2a–d display the characteristic signal of the amide proton
around 8.2 ppm and the 13C spectra show clearly two
chemical shift values near 164 and 180 ppm belonging to
the CONH and the COAr groups, respectively. To obtain
further evidence about the initial geometry, 2D-ROESY
experiments have been performed in D2O for all fluorescent
The purpose here is to check if the new fluorescent moiety
appended to the b-cyclodextrin can induce change in
fluorescence emission upon addition of a guest such
1-adamantanol in aqueous solution. 1-Adamantanol was
chosen for its ability to strongly bind to b-CD and also due
to its non-fluorescent nature, which will not interfere with
subsequent fluorescence measurements.
Figure 2 shows the fluorescence spectra of 2a (2b–d display
the same fluorescent behaviour in studied concentrations)
alone, and in the presence of various concentrations of
1-adamantanol in aqueous solution (phosphate buffer, pHZ
7.0), respectively. Upon addition of 1-adamantanol to an
aqueous solution of 2a, a decrease in the fluorescence
Scheme 2. Preparation of the fluorescent b-cyclodextrins 2a–d.

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F. Delattre et al. / Tetrahedron 61 (2005) 3939–3945
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded with a Bruker AM
400 spectrometer with tetramethylsilane as internal stan-
dard. The abbreviations used are: s (singlet), d (doublet), t
(triplet) and m (multiplet). Mass spectra were measured
using a Platform II Micromass Apparatus. IR spectra were
recorded using a Perkin–Elmer instrument. Melting points
were obtained with a Reichert Thermopan apparatus and are
uncorrected. Fluorescence spectra were recorded using a
Perkin–Elmer LS50B spectrometer. Chromatographic sepa-
rations were carried out on Aldrich G25 and G15. All
reagents were used as purchased unless otherwise stated.
Solvents were dried according to standard procedures.24
All reactions were performed under N2. The reagents were
transferred by syringe
Figure 2. Emission spectra in phosphate buffer (pHZ7.0, 25 8C) of 2a
(0.01 mM) at various concentrations of 1-adamantanol (0–1.8 mM).
intensity with a shift toward shorter wavelength were
observed. The result obtained suggests that the pyridino-
indolizine linker, which is attached onto the primary face of
the b-cyclodextrin, is displaced into a more polar environ-
ment when the 1-adamantanol is added. To calculate the
molecular recognition abilities of 2a–d, the DI/I0 value was
used as the sensitive factor, where DIZI0KI; I and I0 are
the emission intensities in the presence and the absence of
1-adamantanol, respectively. Table 1 shows the DI/I0 values
obtained with 1-adamantanol at 0.1 mM. 2a,b and 2d show
a significant sensitivity factors when recorded in the
presence of 1-adamantanol. Compared to the well known
dansyl appended b-cyclodextrin derivative (DI/I0Z0.390 in
Phosphate Buffer, pHZ7.0),22 2a displays a comparable
sensitivity factor (DI/I0Z0.449) in the presence of 1-ada-
mantanol. On the other hand, 2c shows a surprisingly very
low sensitivity. So in order to examine the possible
correlation between the fluorescence variation and the
bindings ability of the hosts, the binding constants have
been calculated. The guest-induced fluorescence variation
was employed to calculate the binding constants of the
different hosts using the previously method reported by
Ueno.23 The results are shown in Table 1. While 2a, 2b and
2d display almost the same binding behaviour, which is
consistent with the corresponding sensitivity factors
obtained, 2c (RZOCH3) has the strongest binding affinity
and the lowest sensitivity factor. This means that the
sensitivity value given for 2c is relative, and not an absolute,
measure of its sensory ability.
4.1.1. General procedure for the synthesis of 1-substi-
tuted-[4,40] bipyridium bromides 5a–d. The u-brom-
acetophenone compounds 4a–d are commercially available.
A solution of u-bromacetophenone 4a–d (8.8 mmol) in
acetone (200 mL) was added at room temperature to a
solution of bipyridine 3 (1.37 g, 8.8 mmol) in acetone
(100 mL). The solution was warmed to 40 8C for 10 h. The
crude product precipitated, filtered off and washed with
acetone to give colourless solids.
1H and C13 spectra of compound 5a, 5c were consistent with
literature data.25
4.1.2. 1-(4-Methylbenzoylmethyl)-[4,40]bipyridinium
1
bromide (5b). Mp 350 8C. H NMR (DMSO/TMS): dZ
2.46 (s, 3 H, CH3), 6.54 (s, 2 H, CH2NC), 7.51 (d, JZ
8.1 Hz, 2H, Hmeta/CO), 8.01 (d, JZ8.1 Hz, 2H, Hortho/CO),
8.10 (d, JZ5.8 Hz, 2H, Hmeta/N), 8.78 (d, JZ6.6 Hz, 2H,
Hmeta/NC), 8.91 (d, JZ5.8 Hz, 2H, Hortho/N), 9.18 (d, JZ
6.6 Hz, 2H, Hortho/NC); 13C NMR (DMSO/TMS): dZ22.2,
66.6, 122.9, 126.0, 129.3, 130.6, 131.9, 141.7, 146.4, 147.7,
151.9, 153.8, 191.0; IR (KBr): n~Z3024 cmK1, 2949, 1678,
1643, 1602, 1410, 804; MS (ESC, cone 10); m/z (%): 289
(100) [MKBr]; C19H17BrN2O: Calcd C 61.80, H 4.64, N
7.59; found C 62.02, H 4.72, N 7.46.
4.1.3. 1-(4-Chlorobenzoylmethyl)-[4,40]bipyridinium
1
bromide (5d). Mp 350 8C. H NMR (DMSO/TMS): dZ
6.51 (s, 2 H, CH2NC), 7.78 (dd, JZ8.6 Hz, 2H, Hmeta/CO),
8.10 (m, 4H, Hortho/COCHmeta/N), 8.77 (d, JZ6.9 Hz, 2H,
Hmeta/NC), 8.91 (d, JZ4.5 Hz, 2H, Hortho/N), 9.14 (d, JZ
6.9 Hz, 2H, Hortho/NC); 13C NMR (DMSO/TMS): dZ66.0,
122.2, 125.3, 129.5, 130.3, 132.5, 140.0, 141.0, 147.0,
151.2, 153.3, 190.0; IR (KBr): n~Z3018 cmK1, 2927, 1693,
1642, 1588, 1495, 795; MS (ESC, cone 10); m/z (%):309
(100) [MKBrK2], 311 (100) [MKBr]; C18H14BrClN2O:
Calcd C 55.48, H 3.62, N 7.19; found C 55.62, H 3.73, N
7.05.
3. Conclusion
We have described in this paper the synthesis and the
characterisation of a series of new functionalisable fluoro-
phores. For their preparation, a new efficient activated
dipolarophile was developed. The different fluorescence
arms were connected to the primary face of the
b-cyclodextrin leading corresponding fluorescent macro-
cycles in good yields. Fluorescent sensor properties were
also proved through the variation of the fluorescence
emission of 2a–d upon addition of 1-adamantanol. The
preparation, using the second reactive site B, of polymeric
supramolecular systems bearing this new fluorescent moiety
(with and without the cylodextrin moiety) is underway.
4.2. General procedure for the synthesis 3-(4-substi-
tutedbenzoyl)-1-(4-nitrophenylcarbonyl)-7-pyridin-4-
ylindolizines 1a–d
A solution of freshly distilled Et3N (2.7 mmol) was added to

F. Delattre et al. / Tetrahedron 61 (2005) 3939–3945
3943
a stirred solution of 5a–e (2.4 mmol) and 4-nitrophenylpro-
piolate 726 (2.4 mmol) in dry NMP at 0 8C under N2, in the
absence of light. The reaction mixture was maintained at
0 8C over 2 days. The crude product precipitated, filtered
and washed with a large amount of methanol.
129.8, 130.9, 134.6, 137.2, 139.0, 143.5, 145.1, 151.8,
155.3, 160.5, 183.9; IR (KBr): n~Z3069 cmK1, 1728, 1616,
1591, 1469, 1344, 798; MS (ESC, cone 60); m/z (%): 498
(100) [MCH], 500 (32) [MCHC2], 520 (31) [MCNa],
522 (10) [MCNaC2]; C27H16ClN3O5: Calcd C 65.13, H
3.24, N 8.44; found C 65.23, H 3.11, N 8.51.
4.2.1. 3-(Benzoyl)-1-(4-nitrophenoxycarbonyl)-7-pyri-
din-4-ylindolizine 1a. Mp 288–289 8C; 1H NMR
(DMSOC5% CF3COOD/TMS): dZ7.60–7.74 (m, 5H,
Hmeta/NO2CHmeta/COCHpara/CO), 7.90 (d, JZ6.6 Hz,
2H, Hortho/CO), 8.00–7.85 (m, 2H, H03CH06), 8.37 (d, JZ
9.0 Hz, 2 H, Hortho/NO2), 8.60 (d, JZ6.7 Hz, 2H, H02), 8.90
(s, 1H, H05), 9.08 (d, J Z6.7 Hz, 2H, H01), 9.94 (d, JZ
7.9 Hz, 1H, H04); 13C NMR (DMSOC5% CF3COOD/
TMS): dZ105.7, 114.5, 118.3, 123.4, 123.6, 124.5, 125.3,
128.6, 128.7, 128.9, 129.8, 132.4, 134.0, 138.7, 138.8,
143.0, 145.1, 152.5, 155.4, 160.6, 185.2; IR (KBr): n~Z
3060 cmK1, 1727, 1611, 1523, 1478, 1347, 861; MS (ESC,
cone 60); m/z (%): 464 (100) [MCH], 486 (40) [MCNa];
C27H17N3O5: Calcd C 69.97, H 3.70, N 9.07; found C 70.08,
H 3.74, N 8.98.
4.3. General procedure for the synthesis of N-(6A-deoxy-
b-cyclodextrin-6a-yl)-1-amido-3-(4-substitutedbenzo-yl)-
1-(4-nitrophenylcarbonyl)-7-pyridin-4-ylindolizines
2a–d.21
A solution of 1a–d (1 mmol) in dry NMP (10 mL) was
added dropwise to a stirred solution of 9 (1 mmol) in dry
DMF (30 mL) at 50 8C under N2. The reaction mixture was
maintained at 50 8C over 24 h. The yellow solution was then
poured in acetone (300 mL) and the crude compound
collected by filtration. The latter was dissolved in water and
the unreacted starting material 1a–d was removed by
filtration and the filtrate was poured again in acetone
(300 mL). The resultant precipitate was passed through a
CM-25 column by eluting with water. The fractions
containing the fluorescent b-cyclodextrin were combined,
concentrated in vacuum. Finally, the mixture was applied to
gel filtration using Sephadex G-15 to give 2a–d as fine
yellow powders.
4.2.2. 3-(4-Methylbenzoyl)-1-(4-nitrophenoxycarbonyl)-
7-pyridin-4-ylindolizine 1b. Mp 260–261 8C; 1H NMR
(DMSOC5% CF3COOD/TMS): dZ2.43 (s, 3H, CH3), 7.42
(d, JZ8.1 Hz, 2H, Hmeta/CO), 7.63 (d, JZ9.1 Hz, 2H,
Hmeta/NO2), 7.80 (d, JZ8.1 Hz, 2H, Hortho/CO), 7.95 (d,
JZ7.3 Hz, 1H, H03), 7.97 (s, 1H, H06), 8.35 (d, JZ9.1 Hz,
2H, Hortho/NO2), 8.59 (d, JZ6.8 Hz, 2H, H02), 8.87 (s, 1H,
H05), 9.08 (d, JZ6.8 Hz, 2 H, H01), 9.96 (d, JZ7.3 Hz, 1H,
H04); 13C NMR (DMSOC5% CF3COOD/TMS): dZ21.4,
105.4, 114.4, 118.1, 123.4, 123.6, 124.1, 125.3, 128.5,
129.1, 129.3, 129.7, 134.1, 135.9, 138.7, 142.7, 143.6,
145.0, 151.7, 155.3, 184.8; IR (KBr): n~Z3072 cmK1, 1725,
1600, 1522, 1464, 1345, 861; MS (ESC, cone 60); m/z (%):
478 (100) [MCH], 500 (25) [MCNa]; C28H19N3O5: Calcd
C 70.43, H 4.01, N 8.80; found C 70.87, H 4.14, N 8.71.
4.3.1. N-(6A-Deoxy-b-cyclodextrin-6A-yl)-1-amido-3-
benzoyl-7-pyridin-4-ylindolizine 2a. 1H NMR (DMSO/
TMS): 3.25–3.90 (m, 42H, H-2, H-4, H-3, H-5, H-6A,B),
4.28–4.58 (m, 6H, –OH6), 4.84–5.01 (m, 7H, H-1), 5.63–
6.08 (m, 14H, –OH2, –OH3), 7.52–7.76 (m, 4H, H03, H meta/
CO, H para/CO), 7.902 (d, JZ8.3 Hz, 2H, H ortho/CO), 7.94
(d, JZ5.9 Hz, 2H, H 2), 8.21 (s, 1H, H06), 8.39 (m, 1H, NH),
8.73 (d, JZ5.9 Hz, 2H, H01), 9.02 (s, 1H, H05), 9.92 (d, JZ
7.3 Hz, 1H, H04); 13C NMR (DMSO-d6, d): 60.8, 60.9, 71.0,
72.8, 73.2, 74.0, 81.9, 82.3, 82.5, 82.7, 85.1, 102.7, 103.1,
113.8, 117.3, 121.2, 126.4, 128.7, 128.8, 129.3, 131.8,
150.8, 164.2, 185.4; m/z (%): 1481 (MCNa, 100), 1459
(MC1, 15); C63H83N3O36$5H2O: Calcd C 48.87, H 6.05, N
2.71; found C 48.98, H 6.13, N 3.02.
4.2.3. 3-(4-Methoxybenzoyl)-1-(4-nitrophenoxycarbo-
nyl)-7-pyridin-4-ylindolizine 1c. Mp 272–273 8C; 1H
NMR (DMSO C5% CF3COOD/TMS): dZ3.84 (s, 3H,
CH3), 7.15 (d, JZ8.6 Hz, 2H, Hmeta/CO), 7.64 (d, JZ
9.1 Hz, 2H, Hmeta/NO2), 7.87–7.94 (m, 3H, H03CHortho
/
4.3.2. N-(6A-Deoxy-b-cyclodextrin-6A-yl)-1-amido-3-(4-
methylbenzo yl)-7-pyridin-4-ylindolizine 2b. 1H NMR
(DMSO/TMS): 2.44 (s, 3H, –CH3), 3.13–3.84 (m, 42H, H-2,
H-3, H-4, H-5, H-6A,B), 4.38–4.58 (m, 6H, –OH6), 4.78–
4.97 (m, 7H, H-1), 5.58–6.01 (m, 14H, -OH2, OH3), 7.14 (d,
JZ8.8 Hz, 2H, H meta/CO), 7.76 (dd, JZ1.9, 7.4 Hz,1H,
H03), 7.85 (d, JZ5.8 Hz, 2H, H02), 7.89 (d, JZ8.8 Hz, 2H, H
ortho/CO), 8.15 (s, 1H, H06), 8.34 (m, 1H, NH), 8.73 (d, JZ
5.7 Hz, 2H, H01), 8.95 (s, 1H, H05), 9.84 (d, JZ7.4 Hz, 1H,
H04); 13C NMR (DMSO): 21.9, 60.6, 60.9, 71.2, 73.2, 73.3,
73.9, 74.0, 82.1, 82.5 (2!), 85.0, 102.7, 102.7, 103.1,
114.6, 117.8, 121.6, 126.7, 129.3, 130.1, 151.5, 164.3,
185.2; m/z (%): 1495 (MCNa, 100); 1473 (MC1, 18);
C64H85N3O36$5H2O: Calcd C 49.20, H 6.13, N 2.69; found
C 49.28, H 6.10, N 2.73.
CO), 7.95 (s, 1H, H06), 8.36 (d, JZ9.1 Hz, 2H, Hortho/NO2),
8.59 (d, JZ6.7 Hz, 2H, H02), 8.86 (s, 1H, H05), 9.07 (d, JZ
6.7 Hz, 2H, H01), 9.90 (d, JZ7.6 Hz, 1H, H04); 13C NMR
(DMSOC5% CF3COOD/TMS): dZ55.6, 105.6, 114.5,
118.4, 123.4, 123.9, 124.5, 125.4, 127.9, 129.9, 131.0,
131.6, 133.7, 138.6, 142.9, 142.7, 145.2, 152.3, 154.8,
155.2, 160.7, 184.4; IR (KBr): n~Z3078 cmK1, 1723, 1597,
1520, 1478, 1345, 799; MS (ESC, cone 60); m/z (%): 494
(100) [MCH], 516 (40) [MCNa]; C28H19N3O6: Calcd C
68.15, H 3.88, N 8.52; found C 68.23, H 3.92, N 8.43.
4.2.4. 3-(4-Chlorobenzoyl)-1-(4-nitrophenoxycarbonyl)-
7-pyridin-4-ylindolizine 1d. Mp 255–256 8C; 1H NMR
(DMSOC5% CF3COOD/TMS): dZ7.74 (m, 4H, Hmeta
/
NO2CHmeta/CO), 7.90 (d, JZ8.3 Hz, 2H, Hortho/CO), 7.96
(s, 1H, H03), 7.96 (s, 1H, H06), 8.35 (d, JZ8.9 Hz, 2H,
Hortho/NO2), 8.57 (d, JZ6.0 Hz, 2H, H02), 8.86 (s, 1H, H05),
9.06 (d, JZ6.0 Hz, 2H, H01), 9.94 (d, JZ7.0 Hz, 1H, H04);
13C NMR (DMSOC5% CF3COOD/TMS): dZ105.7,
114.6, 118.1, 123.4, 123.6, 124.2, 125.3, 128.5, 128.9,
4.3.3. N-(6A-Deoxy-b-cyclodextrin-6A-yl)-1-amido-3-(4-
methoxybenzoyl)-7-pyridin-4-ylindolizine 2c. 1H NMR
(DMSO/TMS): 3.03–3.88 (m, 42H, H-2, H-3, H-4, H-5,
H-6A,B), 3.95 (s, 3H, –OCH3), 4.33–4.59 (m, 6H, –OH6),
4.78–4.97 (m, 7H, HK1), 5.54–6.07 (m, 14H, –OH2, OH3),

3944
F. Delattre et al. / Tetrahedron 61 (2005) 3939–3945
7. (a) Nakashima, H.; Takenka, Y.; Higashi, M.; Yoshida, N.
J. Chem. Soc., Trans. 2 2001, 2096–2103. (b) Heck, R.;
Marsura, A. Tetrahedron Lett. 2004, 2, 281–284. (c) Corradini,
R.; Dossena, A.; Galaverna, G.; Marchelly, R.; Paragia, A.;
Sartor, G. J. Org. Chem. 1997, 62, 6283–6289. (d) Narita, M.;
Koshizaka, S.; Hamada, F. J. Inclusion Phenom. 1999, 35,
605–610. (e) Teranishi, K.; Komoda, A.; Hisamastu, M.;
Yamada, T. Carbohydr. Res. 1998, 306, 177–187. (f) Tanabe,
T.; Touma, K.; Hamasaki, K.; Ueno, A. Anal. Chem. 2001, 73,
3126–3130. (g) Liu, Y.; Li, L.; Zhang, H. Y.; Liang, P.; Wang,
H. Carbohydr. Res. 2003, 338, 1751–1757.
7.14 (d, JZ8.7 Hz, 2H, H meta/CO), 7.73 (d, JZ7.4 Hz,
1H, H03), 7.89 (d, JZ8.7 Hz, 2H, H ortho/CO), 8.21 (s, 1H,
H06), 8.23 (d, JZ6.1 Hz, 2H, H02), 8.40 (m, 1H, NH), 8.88
(d, JZ6.1 Hz, 2H, H01), 9.03 (s, 1H, H05), 9.82 (d, JZ
7.38 Hz, 1H, H04); 13C NMR (DMSO): 56.4, 60.5, 60.8,
60.9, 71.0, 72.2–74.34, 82.0–82.7, 85.0, 102.6, 102.8, 103.0,
113.8, 114.8, 119.4, 123.4, 126.2, 129.3, 132.3, 146.5,
163.2, 184.5; m/z (%): 1511 (MCNa, 100), 1489 (MCH,
20); C64H85N3O37$6H2O: Calcd C 48.15, H 6.12, N 2.63;
found C 48.23, H 6.30, N, 2.82.
4.3.4. N-(6A-Deoxy-b-cyclodextrin-6A-yl)-1-amido-3-(4-
chlorobenzoy-l)-7-pyridin-4-ylindolizine 2d. 1H NMR
(DMSO/TMS): 3.23–3.90 (m, 42H, H-2, H-4 H-3, H-5,
H-6A,B), 4.20–4.57 (m, 6H, –OH6), 4.76–4.94 (m, 7H, H-1),
5.51–5.99 (m, 14H, –OH2, OH3), 7.64 (d, JZ8.5 Hz, 2H, H
meta/CO), 7.70 (dd, JZ2.4, 7.4 Hz, 1H, H03), 7.81 (d, JZ
8.5 Hz, 2H, H ortho/CO), 7.83 (d, JZ6.1 Hz, 2H, H02), 8.15
(s, 1H, H06), 8.26 (m, 1H, NH), 8.7 (d, JZ6.1 Hz, 2H, H01),
8.94 (s, 1H, H05), 9.87 (d, JZ7.5 Hz 1H, H04); 13C NMR
(DMSO): 60.4, 60.5, 60.8, 71.1, 72.76–74.04, 81.9, 82.0,
82.1, 82.5, 82.6, 82.9, 85.1, 102.7, 102.9, 103.1, 114.4,
117.9, 121.7, 127.1, 129.4, 129.5, 131.7, 151.5, 164.2,
184.2; m/z (%): 1516 (MCNa, 32), 1514 (MCNaK2);
C63H82ClN3O36$5H2O: Calcd C 47.81, H 5.86, N 2.65;
found C 47.98, H 6.00, N 2.75.
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