Enantiomere Erkennungsmechanismen von Cyclodextrinen [Elektronische Ressource] : ein NMR spektroskopischer und gaschromatographischer Ansatz zur Evaluierung der Rolle der Kavität bei enantioselektiven Wechselwirkungen ; Anwendung von Acyclodextrinen in Enantiodiskriminierungsexperimenten = Enantiorecognition mechanism of cyclodextrins / vorgelegt von Giuseppe Sicoli

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Enantiomere Erkennungsmechanismen von Cyclodextrinen: Ein NMR spektroskopischer und gaschromatographischer Ansatz zur Evaluierung der Rolle der Kavität bei enantioselektiven Wechselwirkungen. Anwendung von „Acyclodextrinen“ in Enantiodiskriminierungsexperimenten Enantiorecognition mechanism of cyclodextrins: an NMR spectroscopic and gas-chromatographic approach to evaluate the role of the cavity in the enantioselective interactions. Applications of “acyclodextrins” in enantiodiscrimination experiments DISSERTATION der Fakultät für Chemie und Pharmazie der Eberhard-Karls-Universität Tübingen zur Erlangung des Grades eines Doktors der Naturwissenschaften 2006 vorgelegt von GIUSEPPE SICOLI Tag der mündlichen Prüfung: 26. Januar 2006 Dekan: Prof. Dr. S. Laufer 1. Berichterstatter: Prof. Dr. V. Schurig 2. Berichterstatter: Prof. Dr. K. Albert 3. Berichterstatter: Prof. Dr. W. Lindner, Wien Die vorliegend Arbeit wurde unter der Leitung von Prof. Dr.
Publié le : dimanche 1 janvier 2006
Lecture(s) : 19
Source : W210.UB.UNI-TUEBINGEN.DE/DBT/VOLLTEXTE/2006/2210/PDF/DISSERTATIONGS.PDF
Nombre de pages : 187
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Enantiomere Erkennungsmechanismen von Cyclodextrinen: Ein NMR
spektroskopischer und gaschromatographischer Ansatz zur Evaluierung
der Rolle der Kavität bei enantioselektiven Wechselwirkungen. Anwendung
von „Acyclodextrinen“ in Enantiodiskriminierungsexperimenten



Enantiorecognition mechanism of cyclodextrins: an NMR spectroscopic
and gas-chromatographic approach to evaluate the role of the cavity in the
enantioselective interactions. Applications of “acyclodextrins” in
enantiodiscrimination experiments





DISSERTATION

der Fakultät für Chemie und Pharmazie
der Eberhard-Karls-Universität Tübingen
zur Erlangung des Grades eines Doktors
der Naturwissenschaften



2006

vorgelegt von
GIUSEPPE SICOLI


























Tag der mündlichen Prüfung: 26. Januar 2006

Dekan: Prof. Dr. S. Laufer
1. Berichterstatter: Prof. Dr. V. Schurig
2. Berichterstatter: Prof. Dr. K. Albert
3. Berichterstatter: Prof. Dr. W. Lindner, Wien




Die vorliegend Arbeit wurde unter der Leitung von Prof. Dr. Volker Schurig im der Zeitraum
von November 2002 bis November 2005 am Institut für Organische Chemie der Eberhard-
Karls-Universität Tübingen durchgeführt.





What I see in Nature is a magnificent structure that we can comprehend only very
imperfectly, and that must fill a thinking person with a feeling of humility. This is
a genuinely religious feeling that has nothing to do with mysticism.

Albert Einstein (1879-1955)

















I wish to thank my supervisor Prof. Dr. Volker Schurig for the extremely interesting
discussions about the fascinating world of chirality. I would like to thank all my colleagues
for their continuous assistance.
I also wish to thank the “Graduiertenkolleg – Chemie in Interphasen” for the financial support
of my Ph. D.






























Index



















Index
Index………………………………………………………………………………………........I
Abbreviations………………………………………………………………………..............VII
Summary.....................................................................................................................................1
Introduction………………………………………………….……………………………........7

1. Enantiorecognition mechanism by cyclic and acyclic dextrins: an overview.............. 13
1.1. Enantiodiscrimination in solution..................................................................................... 15
1.2. NMR spectroscopic and CE studies of enantiorecognition.............................................. 15
1.3. Computational studies of cyclodextrins and their derivatives.......................................... 18
1.4 Ability of acyclic oligosaccharides to form complexes and their use for chiral
separation................................................................................................................................. 20
1.5. Enantioselective gas chromatography.............................................................................. 29
1.5.1. CSPs based on amino acid derivatives.......................................................................... 30
1.5.2. CSPs based on cyclodextrin derivatives........................................................................ 30
1.6. Enantioseparation of amino acid derivatives, saturated hydrocarbons, halogenomethanes
and chlorinated/fluorinated ethers (inhalation anaesthetics)……………...………………… 32
1.7. Enantiorecognition mechanism in gas chromatography involving modified
cyclodextrins............................................................................................................................ 37

2. Results and discussion; Part I: Synthesis and characterization of cyclic and acyclic
dextrin derivatives................................................................................................................... 39
2.1. Introduction...................................................................................................................... 41
2.2. Linear dextrins derived from cyclodextrins..................................................................... 42
2.3. Synthesis and characterization of acetyl/TBDMS cyclic and acyclic dextrins by NMR
spectroscopy............................................................................................................................ 43
2.3.1. Heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin 5..................... 46
2.3.2. Heptakis[(2,3-di-O,4’’-O)-acetyl-(1’-O,6-O)-tert-butyldimethylsilyl]-maltoheptaose
(10)…………...……………………………………………………………………………... 49
2.3.3. Octakis[(2,3-di-O,4’’-O)-acetyl-(1’-O,6-O-tert-butyldimethylsilyl)]maltooctaose
(12)......................................................................................................................................... 53
2.3.4. Tris[(2,3-di-O,4’’-O)-acetyl-(1’-O,6-O)-tert-butyldimethylsilyl]-maltotriose (14)….. 53
2.3.5. (2,3,4-tri-O-acetyl-1,6-di-O-tert-butyldimethylsilyl)-D-glucose (16) and (2,3,4-tri-O-
acetyl-1,6-di-O-tert-butyldimethylsilyl)-L-glucose (18)……………………………………. 54
2.4. Synthesis of per-O-methyl-D-maltoheptaose (19)………………………………........... 55
IIIIndex
2.5. Synthesis of D-maltoheptaose bonded to a polydimethylsiloxane via an undecenyl
spacer....................................................................................................................................... 57
2.6. Synthesis of acyclic ‘Lipodex E’ (28).............................................................................. 60
2.7. Molecular modeling analysis............................................................................................ 62

3. Results and discussion; Part II: Enantiorecognition by NMR spectroscopy in
solution.................................................................................................................................... 65
3.1. Introduction...................................................................................................................... 67
3.2. Enantiodiscrimination of halogenated compounds……………...................................... 68
3.2.1. Enantiodiscrimination of ‘compound B’ by CD 7 (5)................................................... 71
3.3. Premilinary study of ‘acyclodextrins’ in solution............................................................ 85

4. Results and discussion; Part III: Enantioseparation by gas chromatography................ 91
4.1. Introduction...................................................................................................................... 93
4.2. Enantioseparation of halogenated anaesthetics and ‘compound B’................................. 93
4.3. Enantioseparation of α-amino acid derivatives................................................................ 96
4.4. Further enantioseparation of various derivatized and underivatized compounds............ 98
4.5. How does the degree of oligomerization in acyclic dextrins affect the
enantioselectivity....................................................................................................................108
4.6. Preliminary study on acyclic dextrins with differrent derivatization patterns.................113
4.7. Enantioseparation of saturated aliphatic hydrocarbons...................................................118
4.8. Thermodynamic data obtained from retention increment R’ analysis.............................122

Conclusions............................................................................................................................125

Experimental section............................................................................................................131
Materials and Methods...........................................................................................................133
Heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)- β-cyclodextrin (5)...........................134
Hexakis(2,3-di-O-acetyl-6-O-terteα4) ...........................134
Octakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-γ-cyclodextrin (6)..............................134
Heptakis[(1’-O,6-O)-tert-butyldimethylsilyl]-maltoheptaose (9)..........................................135
Heptakis[(2,3-di-O,4’’-O)-acetyl-(1’-O,6-O)-tert-butyldimethylsilyl]-maltoheptaose (10)..135
Octakis[(1’-O,6-O)-tert-butyldimethylsilyl]-maltooctaose (11).............................................136
Octakis[(2,3-di-O,4’’-O)-acetyl-(1’-O,6-O)-tert-butyldimethylsilyl]-maltooctaose (12)…..136
IV

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