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Application of HRMAS 1H NMR Spectroscopy To Investigate Interactions between Ligands and Synthetic Receptors.

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7.7 mmol). The solution was stirred 0.5 h at 78 8C and then
another 5 h at RT. The resulting solution was added dropwise at
78 8C to a solution of ClP¼C(SiMe3)2 (1.74 g 7.7 mmol) in
diethyl ether (30 mL). After stirring for 1 h at low temperature
the solvent was removed under reduced pressure. The residue
dissolved in n-hexane and then filtrated. After concentration of
the filtrate solution 1 a precipitates in crystalline form as
isomeric mixture rac/meso-1 a ¼ 4:1. MS (16 eV): m/z (%) ¼
636 (8) [M]þ , 562 (66) [MSiMe3]þ , 73 (100) [SiMe3]þ ;
P NMR(CH2Cl2, 25 8C): d ¼ 386.2, 388.1 ppm (rac/meso-1 a).
a) D. Jerchel, S. Noetzel, K. Thomas, Chem. Ber. 1960, 93, 2966 ±
2970; b) M. D. Rausch, D. J. Ciapenelli, J. Organomet. Chem.
1967, 10, 127 ± 136.
The free l-N2P2[CH(SiMe3)2]2 ligand 4 prefers a syn-chair-chair
conformation in the solid state.[8] The ligand 5 retains the
conformation of the ate-complex 3. S. Ekici, M. Nieger, E.
Niecke, unpublished results.
H. J. Kr¸ger, Chem. Ber. 1995, 128, 531 ± 539.
Selected bond lengths [pm] and angles [8] of 2. Li1-N1 209.7(8),
Li1-N33 211.8(7), Li1-P1 244.5(7), Li1-P2 250.1(7); N1-Li1-N33
86.9(3), N1-Li1-P1 87.3(3), N1-Li1-P2 86.9(3), N33-Li1-P1
86.2(3), N33-Li1-P2 87.4(2), P1-Li1-P2 171.6(3). The analogous
phosphamethanide-complex bearing four SiMe3 groups instead
of the four phenyl groups in 2 has a similar structure.[9]
Crystal data: 3: C55H115ClFeLi3N7P2Si6, Mr ¼ 1217.14, triclinic,
space group P
1 (no. 2), a ¼ 13.6549(1), b ¼ 14.6901(2), c ¼
19.2675(2) ä, a ¼ 102.043(1), b ¼ 92.848(1), g ¼ 103.988(1)8,
V ¼ 3647.28(7) ä3, Z ¼ 2, m(MoKa) ¼ 0.422 mm1, F(000) ¼ 1320,
43 173 reflections (2qmax ¼ 508), thereof 12 849 unique, wR2(F2) ¼
0.1142, R(F) ¼ 0.0406, 670 parameters, 309 restraints. 2:
C72H106Li2N2O5Si4, Mr ¼ 1267.77; orthorhombic, space group
(no. 19),
a ¼ 16.8587(2),
b ¼ 20.3906(3),
21.2944(3) ä, V ¼ 7320.1(2) ä3, Z ¼ 4, m(MoKa) ¼ 0.173 mm1,
F(000) ¼ 2736, 70 978 reflections (2qmax. ¼ 508), thereof 12 972
unique, wR2(F2) ¼ 0.2342, R(F) ¼ 0.0766, 759 parameters, 505
restraints. The absolute configuration could not be determined
reliably (x ¼ 0.40(14)). 6: C52H68CuN2P2Si4þ CF3SO3, Mr ¼
1107.99, triclinic, space group P
1 (no. 2), a ¼ 11.2089(5), b ¼
15.2256(7), c ¼ 18.0123(10) ä, a ¼ 99.324(2), b ¼ 91.194(2), g ¼
111.352(2)8, V ¼ 2814.5(2) ä3, Z ¼ 2, m(MoKa) ¼ 0.619 mm1,
F(000) ¼ 1164, 13085 reflections (2qmax. ¼ 508), thereof 9316
unique, wR2(F2) ¼ 0.2148, R(F) ¼ 0.0802, 606 parameters, 581
restraints (disordered CHTms2 groups). 7: C38H69NOP2Si6FeNi¥Et2O, Mr ¼ 975.10, triclinic, space group P
1 (no. 2), a ¼
15.0304(1), b ¼ 18.0995(2), c ¼ 20.0055(2) ä, a ¼ 85.709(1), b ¼
88.418(1), g ¼ 69.915(1)8, V ¼ 5097.0(1) ä3, Z ¼ 4, m(MoKa) ¼
0.891 mm1, F(000) ¼ 2088, 65 240 reflections (2qmax ¼ 508),
thereof 17 943 unique, wR2(F2) ¼ 0.1170, R(F) ¼ 0.0424, 986
parameters, 92 restraints (disordered solvent Et2O). All structure data were collected on a Nonius KappaCCD diffractometer
using MoKa-radiation. The structures were solved by direct
methods (SHELXS-97) and refined anistropically on F2, the Hatoms were refined using a riding model (SHELXL-97). CCDC181615 (2), CCDC-181616 (3), CCDC-190910 (6), and CCDC190911 (7) contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge via (or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (þ 44) 1223-336-033; or deposit SHELXS-97: G. M. Sheldrick, Acta Crystallogr. Sect. A 1990, 46, 467 ± 473 SHELXL-97: G. M. Sheldrick,
Universit‰t Gˆttingen, 1997.
a) H. H. Karsch, G. M¸ller, J. Chem. Soc. Chem. Commun. 1984,
569 ± 570; b) W. Clegg, S. Doherty, K. Izod, P. O©Shaughnessy,
Chem. Commun. 1998, 1129 ± 1130, and references therein.
™Structures of Lithium Salts of Heteroatom Compounds∫: F.
Pauer, P. P. Power in Lithium Chemistry (Eds.: A.-M. Saspe,
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
P. von Rague Schleyer), Wiley-Interscience, New York, 1995,
p. 295.
M. Melnik, L. Macaskova, C. E. Holloway, Coord. Chem. Rev.
1993, 126, 71 ± 92.
CuI-complexes of diazapyridinophanes do not display geometries that are comparable to 6; H. J. Kr¸ger, personal communication.
The polarized UV/Vis absorption spectra were recorded using a
particular micro single-crystal UV/Vis spectrometer. Details
about this instrument are prevalent in the literature: E. Krausz,
Aust. J. Chem. 1993, 46, 1041 ± 1054. The investigated crystal of
compound 6 had a cross-section of 0.20 î 0.08 mm2, (thickness
0.05 mm), the crystal of compound 4 was notably smaller with a
cross-section of 0.10 î 0.05 mm2 (thickness ¼ 0.05 mm).
J. Grobe, N. Krummen, R. Wehmschulte, B. Krebs, M. L‰ge, Z.
Anorg. Allg. Chem. 1994, 620, 1645 ± 1658.
CV: v ¼ 200 mV s1; CH2Cl2/nBu4NBF4 0.1m ; calomel/GCE/Pt
(GCE ¼ glassy carbon electrode). MeCN/nBu4NPF6 ; reference
electrode: calomel E ¼ 0.24 V; IR-compensation (kW) 3: 2.5; 5,
6: 0.2; 7: 4.5.
HRMAS NMR Spectroscopy
Application of HRMAS 1H NMR Spectroscopy
To Investigate Interactions between Ligands and
Synthetic Receptors**
Heidi H‰ndel, Elke Gesele, Klaus Gottschall, and
Klaus Albert*
Dedicated to Professor G¸nther Jung
on the occasion of his 65th birthday
Molecular recognition processes are predicted to become the
basis of all advanced separation techniques. The investigation
of intermolecular interactions in the interphase between a
chromatographic support and a substrate dissolved in a
mobile phase is the crucial condition for understanding
chromatographic separation mechanisms and for the design
of tailored stationary phases. In solution and also in suspension ligand±receptor interactions can be studied using methods of high-resolution (HR) NMR spectroscopy, for example
by employing the nuclear Overhauser enhancement (NOE)
[*] Prof. Dr. K. Albert, Dr. H. H‰ndel, Dr. E. Gesele
Institut f¸r Organische Chemie
Universit‰t T¸bingen
Auf der Morgenstelle 18, 72076 T¸bingen (Germany)
Fax: (þ 49) 7071-295-875
Dr. K. Gottschall
Dr. Gottschall INSTRUCTION
Gesellschaft f¸r Technische Chromatographie mbH
Donnersbergweg 1, 67059 Ludwigshafen (Germany)
[**] This work was funded by Dr. Gottschall INSTRUCTION mbH,
Ludwigshafen. HRMAS ¼ high-resolution magic-angle spinning.
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Angew. Chem. Int. Ed. 2003, 42, No. 4
or 2D NOESY technique.[1] The NOE can provide information on the distance between protons in close spatial
proximity[1] within a given molecule and can also be used to
detect ligand±receptor interactions in complex mixtures
(bioaffinity NMR spectroscopy)[2] and in solutions of chiral
selectors and optical isomers.[3] Specific interactions between
macromolecules and low-molecular-weight compounds (ligands or substrates) with equilibrium constants K in the mm
to mm range, the so-called fast-exchange regime, are revealed
by the transferred NOE (trNOE) effects.
High-molecular-weight compounds, such as proteins or
polymers, exhibit a strong negative NOE effect with a fast
build-up rate. If a low-molecular-weight compound binds to a
macromolecule, it acquires the motional correlation time tC of
the macromolecule thus developing a negative NOE in the
bound state. This negative NOE will be transferred to the
NOE cross-peaks associated with the free ligand (in fast
exchange within the NMR time scale) to an extent which
depends on the lifetimes in the free and bound states and the
spin-lattice relaxation times in the free state.
If there is a binding equilibrium between a small-molecule
ligand and a polymeric support, the intramolecular NOEs
normally observed for free ligands alone (typically weak
positive NOEs) will exhibit increased negative amplitudes
because of the trNOE effect. The trNOE effect, however,
vanishes for weak affinities as well for high affinities. A
particular advantage of the trNOE is that it can be detected
even in the presence of a large free-ligand excess. Furthermore, since the trNOE derives from the bound state, it
strongly depends on the interproton distance providing
information upon the geometry of the ligand in the bound
state.[1] Thus, a weaker trNOE could be the result of a slightly
increased interproton distance or of a weaker binding affinity
between the ligand the polymeric support.
trNOE measurements are performed for the detection of
interactions between biologically active compounds (e.g.
saccharides and their derivatives) and proteins and for the
fast screening of substance libraries for new active compounds.[4±7]
In the field of separation science NMR spectroscopic
investigations have been performed mainly for the characterization of stationary phases. Here, the application of solidstate NMR spectroscopy resulted in a deeper understanding
of the structure and dynamics of stationary phases.[8±14] The
investigation of interactions between analytes and chromatographic supports in the presence of a mobile phase is feasible
with the help of HR magic-angle spinning (HRMAS) NMR
spectroscopy. This technique allows the application of HR
NMR spectroscopy to suspended solid- or gel-like samples.
Under MAS conditions spectral resolution can approach the
typical values obtainable in the liquid state. Thus, an insoluble
sample swollen in an appropriate solvent can be rapidly
characterized by HRMAS 1H NMR spectroscopy.[15±20]
We have utilized 2D NOESY techniques together with
HRMAS 1H NMR spectroscopy to characterize the interactions between new chromatographic supports and the
following low-molecular-weight compounds containing secondary amine, carbonyl, and carboxy groups: methylphenylsuccinimide (1), methylphenylhydantoin (2), and phenylproAngew. Chem. Int. Ed. 2003, 42, No. 4
pionic acid (3). The current investigations are focussed at
obtaining a qualitative insight into the role of hydrogenbonding, ionic, and hydrophobic interactions. Two new coated
silica-gel chromatographic supports have been investigated: 4
with a polyvinylamine coat containing 8 % formamide groups
and 5 with a polyvinylamine coat containing 14 % benzylcarbamate groups.[21]
Figure 1 shows the HRMAS 2D NOESY spectrum in D2O
for a suspension of 1 and silica gel coated with 4. The ligand in
solution (fast exchange between free and bound forms) shows
well-resolved narrow signals while the polymer gel gives
broad signals for CH and CH2 protons. The strongest crosspeak is that between the unresolved phenyl-group signal (d ¼
7.3 ppm) and the singlet of the methyl group (d ¼ 1.65 ppm)
of the ligand, and is negative because of the trNOE effect and
the binding equilibrium. If the ring CH2 group in 1 is replaced
by an NH group as in 2, the interaction between ligand and
polymer is increased, as reflected in a twofold increase in the
negative amplitude for the phenyl–CH3 cross-peak observed
for ligand 2 versus ligand 1.
Hydrophobic interactions between receptor and ligand
are expected to dominate with water as a solvent. Therefore,
the binding energy observed for 1 should exceed that of 2
because 1 is less polar, less soluble in water, and has a larger
hydrophobic contact area. Despite the aqueous environment,
hydrogen bonds seem to be responsible for the observed
binding energies of the investigated ligands: the hydantoin
can engage in more hydrogen bonds simultaneously than the
The interaction of 2 with the silica-gel coating 5 is also
sensitive to changes in the solvent composition of the mobile
phase. Various D2O/[D3]acetonitrile mixtures (100/0, 90/10,
10/90, and 0/100) were investigated, and the phenyl±CH3
cross-peak integrals for ligand 2 were evaluated (Figure 2).
The negative cross-peak integral is three-times larger in
100 % D2O than in 100 % [D3]acetonitrile, which indicates
that water increases the equilibrium constant for binding in 2.
However, the minimum NOE amplitude was obtained in
D2O/[D3]acetonitrile 10/90 The same solvent effect is also
reflected in the chromatographic retention data for 2, for
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Figure 1. HRMAS 2D NOESY spectrum (400 MHz) of a suspension containing 1 and silica gel coated with the 4 in D2O (300 K, mixing time
100 ms). The 1D HRMAS 1H NMR spectrum of 1 together with the stationary phase 4 is depicted in the F2 and the F1 directions. The narrow signals of the substrate are labeled in the 1D trace with roman letters; the broad signals of the coating 4 of the swollen polymeric phase are labeled
with italic letters. Only a negative intramolecular phenyl±CH3 cross-peak (trNOE) was observed (correlation depicted in blue).
Figure 2. Relative integrals for the negative intramolecular NOE crosspeak between the phenyl and methyl groups of 2 in a suspension of 2
and silica gel coated with the 5 in D2O/[D3]acetonitrile solvent mixtures.
which a maximum retention occurs at 100 % water.[21] To
discriminate between polar and nonpolar binding contributions as a function of the solvent composition is a major
objective of ongoing investigations.
NOE measurements can also be used to investigate the
efficiency of various stationary phases for binding 3. Dis-
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Figure 3. Relative integrals for the intramolecular phenyl±CH2 NOE
cross-peak recorded in D2O for 3 alone (a) and in suspensions containing: silica gel (b), aminopropyl silica gel (c), polyvinylamine 5
(Mr ¼ 10 000±20 000 Dalton) (d), silica gel coated with 5 (e).
solved in D2O compound 3 exhibits a weak positive NOE
between the aromatic ortho protons of the phenyl rings and
the neighboring methylene protons at C-3 (Figure 3 a). This
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Angew. Chem. Int. Ed. 2003, 42, No. 4
Figure 4. HRMAS 2D NOESY spectrum (400 MHz) of a suspension containing dissolved 3 and silica
gel coated with 4 in D2O (300 K, mixing time 100 ms). Substrate and are labeled with roman letters
and polymer signals with italic letters. Only negative intramolecular (correlation depicted in blue)
and intermolecular (correlation depicted in red) trNOE cross-peaks are observed.
NOE did not change when underivatized silica gel was added
(Figure 3 b), which indicates very weak or even no binding of
ligand 3. With aminopropyl silica gel coated in 4 as the
stationary phase a weak negative NOE is observed (Figure 3 c), corresponding to a trNOE effect as a result of a
moderate ligand±polymer interaction. A slightly larger negative NOE is observed in the presence of the pure derivatized
5 which had not been immobilized to silica gel (Figure 3 d).
Finally, when polymer 5 was immobilized on silica gel, the
negative phenyl±CH2 cross-peak intensity increased eightfold
(Figure 3 e). This phenomenon may be explained by the
increase in the effective correlation time tC for the polymer
when bound to the silica gel together with an significant
increase of the equilibrium constant K for the ligand±receptor
The interaction between 3 and silica gel coated with the 4
was illustrated in more detail by the HRMAS 2D NOESY
experiment shown in Figure 4. Negative intramolecular
NOEs were observed for the phenyl protons to methylene
protons on C-2 and C-3 of the ligand. In addition, a negative
intermolecular cross-peak was observed arising from the
phenyl protons (also from the protons on C-2 and C-3) of the
ligand to CH2 groups of the polymer backbone of the
stationary phase.
Angew. Chem. Int. Ed. 2003, 42, No. 4
Isooctane was used as a reference ligand which did not interact
with the investigated stationary
phases and exhibited no trNOEs
for any of the systems studied. This
result indicates that a hydrophilic
interaction may be prerequisite for
additional hydrophobic effects.
The model ligands employed
here and the 2D NOESY data
obtained in the presence of several
stationary phases illustrate how the
trNOE can be used to evaluate
ligand binding affinities of novel
synthetic receptors developed for
separation or binding purposes. We
could show that HRMAS 1H NMR
spectroscopy and 2D NOESY experiments can be efficiently used to
observe interactions between the
analyte and the stationary phase as
well as the influence of chemical
modifications of the stationary
phase and the contribution of solvent effects. Thus, the trNOE effect
can provide valuable information
for the design and implementation
of novel, task-specific or tailored
stationary phases. In addition,
become a potent method for visualizing the binding epitopes in molecular recognition processes.
Experimental Section
All NMR spectroscopic studies were conducted at 400 MHz with a
Bruker ARX-400 NMR spectrometer equipped with an HRMAS
accessory. HRMAS 1H NMR spectra were recorded with 4 mm ZrO2
rotors (detection volume 60 mL) at a rotation rate of 4500 Hz at
300 K. Ligand concentrations in stock solutions were 0.1 mol L1 (the
concentration of ligand 3 was lower for solubility reasons). Suspensions were prepared by adding the stationary phase (3.5 mg) to the
stock solution (60 mL). According to the total number of monomer
units in the polymer the receptor concentration was approximately
145 mm, the amount of strong binding sites was estimated to 1±3 %.
The standard phase-sensitive 2D NOESY pulse sequence was
modified to include solvent suppression, either by presaturation for a
single solvent peak (D2O) or using frequency-selective 908 pulses
(Gaussian) for multicomponent solvents. 2D NOESY spectra of
ligands alone were recorded with a mixing time of 900 ms; for ligand±
polymer mixtures a mixing time of 100 ms was used. A total of
512 increments with 128 transients and 1 K data points with a spectral
width (SW) of 8 kHz were acquired in both dimensions for the 2D
NOESY spectra. A zero filling up to 1 K data points in the F1
dimension and multiplication with a shifted sine bell function
(factor 2) in both dimensions were performed. Phase correction was
performed to give negative absorption lineshapes for diagonal peaks
in both dimensions. Positive and negative NOEs then result in
positive and negative cross-peaks, respectively.
Received: August 5, 2002 [Z19893]
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Molecular Knots
[1] D. Neuhaus, M. P. Williamson, The Nuclear Overhauser Effect in
Structural and Conformational Analysis, Wiley-VCH, Weinheim,
[2] W. Jahnke, H. C. Kolb, M. J. J. Blommers, J. L. Magnani, B.
Ernst, Angew. Chem. 1997, 109, 2715 ± 2719; Angew. Chem. Int.
Ed. Engl. 1997, 36, 2603 ± 2607.
[3] N. M. Maier, S. Schefzick, G. M. Lombardo, M. Feliz, K.
Rissanen, W. Lindner, K. B. Lipkowitz, J. Am. Chem. Soc.
2002, 124, 8611 ± 8629.
[4] a) B. Meyer, T. Weimar, T. Peters, Eur. J. Biochem. 1997, 246,
705 ± 709; b) T. Peters, B. Meyer, DE-B 19649359 1996; [ Chem.
Abs. 1998, 128, 17 7880z].
[5] D. Henrichson, B. Ernst, J. L. Magnani, W.-T. Wang, B. Meyer, T.
Peters, Angew. Chem. 1999, 111, 106 ± 110; Angew. Chem. Int.
Ed. 1999, 38, 98 ± 102.
[6] H. Maaheimo, P. Kosma, L. Brade, H. Brade, T. Peters,
Biochemistry 2000, 39, 12 778 ± 12 788.
[7] F. Casset, T. Peters, M. Etzler, E. Korchagina, N. Nifant©ev, S.
Pÿrez, A. Imberty, Eur. J. Biochem. 1996, 239, 710 ± 719.
[8] H. O. Fatunmbi, M. D. Bruch, M. J. Wirth, Anal. Chem. 1993, 65,
2048 ± 2054.
[9] A. B. Scholten, J. W. de Haan, H. A. Claessens, L. J. van de Ven,
C. A. Cramers, Langmuir 1996, 12, 4741 ± 4757.
[10] K. Albert, T. Lacker, M. Raitza, M. Pursch, H.-J. Egelhaaf, D.
Oelkrug, Angew. Chem. 1998, 110, 809 ± 812; Angew. Chem. Int.
Ed. 1998, 37, 777 ± 780.
[11] K. Albert, TrAC Trends Anal. Chem. 1998, 17, 648 ± 658.
[12] M. Pursch, L. C. Sander, K. Albert, Anal. Chem. 1999, 71, 733A741A.
[13] M. Raitza, J. Wegmann, S. Bachmann, K. Albert, Angew. Chem.
2000, 112, 3629 ± 3632; Angew. Chem. Int. Ed. 2000, 39, 3486 ±
[14] S. Bachmann, C. Hellriegel, J. Wegmann, H. H‰ndel, K. Albert,
Solid State Nucl. Magn. Reson. 2000, 17, 39 ± 51.
[15] P. C. Anderson, M. A. Jarema, M. J. Shapiro, J. P. Stokes, M.
Ziliox, J. Org. Chem. 1995, 60, 2650 ± 2651.
[16] P. A. Keifer, L. Baltusis, D. M. Rice, A. A. Tymiak, J. N.
Shoolery, J. Magn. Reson. Ser. A 1996, 119, 65 ± 75.
[17] P. A. Keifer, J. Org. Chem. 1996, 61, 1558 ± 1559.
[18] M. Pursch, G. Schlotterbeck, L.-H. Tseng, K. Albert, W. Rapp,
Angew. Chem. 1996, 108, 3034 ± 3036; Angew. Chem. Int. Ed.
Engl. 1996, 35, 2867 ± 2869.
[19] L.-H. Tseng, D. Emeis, M. Raitza, H. H‰ndel, K. Albert, Z.
Naturforsch. B 2000, 55, 651 ± 656.
[20] J. Klein, R. Meinecke, M. Mayer, B. Meyer, J. Am. Chem. Soc.
1999, 121, 5336 ± 5337.
[21] Dr. Gottschall Instruction, DE-19855173 2000, PCT/EP99/
09200 (WO 0032649), 2000, PCT/EP/09199 (WO 0032648), 2000,
[ Chem. Abs. 2000, 133, 18 027p], [ Chem. Abs. 2000, 133,
31 037m].
[22] G. Gottschall, unpublished results.
A Topologically Chiral Molecular Dumbbell**
Oleg Lukin, Janosch Recker, Athanasia Bˆhmer,
Walter M. M¸ller, Takateru Kubota, Yoshio Okamoto,
Martin Nieger, Roland Frˆhlich, and Fritz Vˆgtle*
™Knotaxanes∫,[1] as we call the hitherto unknown rotaxanes
bearing knots as stoppers, are an as yet unrealised dream in
topological chemistry.[2] A prerequisite for these systems is a
™dumbbell∫[3] in which at least one molecular knot forms the
topologically chiral stoppers. To connect two molecular knots
in such a way necessitates the availability of a monosubstituted knot. Our recent efforts involved removal of one
to three benzyl groups from the periphery of tris(benzyloxy)knotane to yield an inseparable mixture of hydroxyknotanes.[4] We have now extended the idea of protecting-group
chemistry in the knotane architecture to synthesize the
tris(allyloxy)knotane 1 in 5 % yield by utilizing our already
well-developed one-pot procedures for the preparation of
amide-based knots.[5, 6]
Twelve of the reaction batches were collected and purified
by column chromatography and resulted in 1 g of the knotane
1, which gave diffraction-quality crystals upon recrystallization from CHCl3/CH3OH. Single-crystal X-ray analysis[7]
revealed (Figure 1) that molecule 1 is indeed a chiral knotted
structure and adopts a conformation which is very similar to
that of the unsubstituted knot:[5] all the 2,6-pyridindicarbamide moieties form outer edges of the three loops of the
[*] Prof. Dr. F. Vˆgtle, Dr. O. Lukin, Dr. J. Recker, Dipl.-Chem. A. Bˆhmer,
W. M. M¸ller
Kekulÿ-Institut f¸r Organische Chemie und Biochemie
Rheinische Friedrich-Wilhelms-Universit‰t Bonn
Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
Fax: (þ 49) 228-73-5662
Dr. T. Kubota, Prof. Dr. Y. Okamoto
Department of Applied Chemistry
Graduate School of Engineering, Nagoya University
Chikusa-ku, Nagoya, 464-8603 (Japan)
Dr. M. Nieger
Institut f¸r Anorganische Chemie
Rheinische Friedrich-Wilhelms-Universit‰t Bonn
Gerhard-Domagk-Strasse 1, 53121 Bonn (Germany)
Dr. R. Frˆhlich
Organisch-chemisches Institut
Universit‰t M¸nster
Corrensstrasse 40, 48149 M¸nster (Germany)
[**] A part of this work was presented on September 9, 2002 at the ™14th
International Symposium on Chirality∫ in Hamburg. Financial
assistance by the Deutsche Forschungsgemeinschaft is gratefully
acknowledged (Sonderforschungsbereich 624). O.L. thanks the
Alexander von Humboldt Foundation for a fellowship. We would
also like to express our thanks to Mr. S. Bitter and Mr. S. Buschbeck
for recording MALDI-TOF mass spectra and Dr. C. A. Schalley for
helpful discussions.
Supporting information for this article is available on the WWW
under or from the author.
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1433-7851/03/4204-0442 $ 20.00+.50/0
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synthetic, spectroscopy, interactions, nmr, application, investigated, hrmas, receptors, ligand
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