Synthese von cyclischen Disacchariden durch intramolekulare Glycosylierung [Elektronische Ressource] / vorgelegt von Patrick Claude

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SYNTHESE VON CYCLISCHEN DISACCHARIDEN DURCH INTRAMOLEKULARE GLYCOSYLIERUNG Dissertation der Fakultät Chemie-Pharmazie der Eberhard-Karl- Universität Tübingen zur Erlangung des Grades eines Doktors der Naturwissenschaftten 2005 vorgelegt von

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• Publié par: eberhard_karls_universitat_tubingen
• Publié le: 01 janvier 2005
• Nombre de lectures: 23
• Langue: Deutsch
• Poids de l'ouvrage: 2 Mo

Exrait

SYNTHESE VON CYCLISCHEN


DISACCHARIDEN


DURCH


INTRAMOLEKULARE GLYCOSYLIERUNG






Dissertation



der Fakultät Chemie-Pharmazie

der Eberhard-Karl- Universität Tübingen


zur Erlangung des Grades eines Doktors

der Naturwissenschaftten




2005


vorgelegt von

Patrick Claude



































Tag der Mündlichern Prüfung: Juni 3 2005



Dekan : Prof. Dr.rer.nat. S. Laufer


1. Berichterstatter: Prof. Dr. rer. nat. T. Ziegler

2. Berichterstatter: Prof. Dr. rer. nat. M. Maier








Aknowledgements



My scientific research work has been carried out partially at the University of Cologne
and, University of Tübingen under the supervision of Professor Dr. Thomas Ziegler, to
whom I would like to express my warmest gratitude for communicating to me his
fruitful instructions and knowledge in exploring the vast and important specialty of
carbohydrate chemistry that allowed me to grow as an organic chemist.


I express my best thanks to

To the members of the jury Professor Dr. Thomas Ziegler, Professor Dr. Martin Maier,
Professor Dr. Lars Wesemann, Professor Dr. Stefan Laufer, and Professor Dr. Ulrich Nagel for
taking their precious time to read and appreciate my written thesis.

Dr. Subramanian for his disponibility and very fruitful scientific and administrative advices.

Dr. H Schmickler at the University of Cologne for the numerous measurements of one and
two dimensional-NMR spectroscopies, and also for his very fruiful advices concerning the
NMR analysis.

Mrs. Hoven at the University of Cologne for the NMR –measurements.

Mr. Paul Schuler from the University of Tübingen for measuring the NMR –spectrums from
the 600 MHz instrument, and for taking his time to install the X-Win-NMR 3.0 program for
our working group.

Mrs. NGuyen for the one and two dimensional spectrum measurements on the 400Mhz.

Dr. H. Müller and Mr.G. Nicholson for the High Resolution Mass Spectroscopy
measurements.

Dr. Christian Lehman from the University of Lausanne who graciously accepted our
invitation by taking his precious time to hold an important seminar about Molecular
Modelling to our institute and his important lecture to our working group.
I thank him very much for the molecular modelling measurements of my compounds
and his instructing advices.

Dr. Gregor Lemanski for his good scientific advices.

To all the collegues from the group of Pr. Dr. Thomas Ziegler for the creative atmosphere
and research discussions.


























The beauty of scientific research is the endless learning

process and adventure, that leaving us so many

universes to discover which requires

on our part , regardless our level

Wisdom and modesty























Dedication


I dedicate my thesis to my wonderful parents who endlessly manifested toward me

their deepest affection and support throughout all the all the delicate periods of my life.

I am so lucky to have you as parents, and I deeply love you


To the rest of my family who showed me much mental support during this crucial period of my

dissertation, and to the good friends of the family as well as mines who manifested the same

support.

I thank you very much, you all have my great considerations.





















TABLE OF CONTENTS


1. Abbreviations
2. Introduction............................................................................................................ 1-8
3. Chapter I.
Leaving Group Bases Intramolecular Glycosylation................................................10- 29
4. Chapter II.
Linkage of the Accepting Atom via Bifunctional Group. .......................................30 - 62
5. Chapter III.
Spacer- Mediated Linkage via Nonreacting Centers..............................................63 - 115
6. Chapter IV.
Intramolecular Glycosylation via Succinylamide alkyl Spacer and
Molecular Modelling........................................................................................... 116 - 161
7. Experimental Part.
Instrumentation, reagents and material. ................................................................ 162 - 163
Nomencature of synthesized compounds. ............................................................. 164 - 166
Experimental Procedures. ..................................................................................... 167 - 187
8. Zuzammenfassung (Summary). ..........................................................................188 -193
9. Bibliography. .................................................................................................... 194 - 198














Abbreviations


Ac Acetyl

Ac O Acetic anhydride 2

AgOTf Silver trifluoromethanesulphonate

Bn Benzyl

BnBr Benzyl bromide

Bz Benzoyl

BzCl Benzoyl chloride

BF Et O Boron trifluoride etherate 3. 2

Bu SnO Dibutyl tin oxide 2

(Bu) NHSO Tetrabutylammoniumhydrogensulphate 4 4

t Bu tert-Butyl

CH Cl Dichloromethane 2 2

CH I Methyl iodide 2 2

Ce(NH ) NO Cerium(IV) ammonium nitrate 4 4 3

CsF Cesium fluoride

COSY Correlated Spectroscopy

DAST Dimethylaminosulfurtrifluoride

DCC N,N-Dicyclohexylcarbodiimide

DCE Dichloroethane

DDQ 2,3-Dichloro-5,6-dicyano-p-benzochinone

DEPT Distortionless Enhancement by Polarization Transfer

DMAP 4-(Dimethylamino) pyridine

DMST Dimethyl (methylthio)sulphonium triflate


DMF N,N-Dimethylformamide

DTBP 2,6-di-tert-butyl-pyridine

DTBMP 2,6-di-tert-butyl-methylpyridine

Et O Diethylether 2

EtOH Ethanol

EtOAc Ethyl acetate

Et N Triethyl amine 3

Fmoc 9-Fluorenylmethoxycarbonyl

Fuc Fucose

Gal. Galactose

Glc Glucose

GlcNAc N-Acetylglucosamine

h Hour

HBr Hydrobromic acid

HCl Hydrochloric acid

HCO H Formic acid 2

H SO Sulfuric acid 2 4

HPLC High pressure liquid chromatography

HMBC Heteronuclear multi-bond correlation

HV High vacuum

HOBt 1-Hydroxy- benzotriazol

Man Mannose

MeOH Methanol

MeOTf Methy Triflate

MeCN Acetonitrile

min Minute

Ms Mesylate

MBnBr Methoxybenzyl bromide

Me SiCl Dimethylsilyl chloride 2 2

MeNO Nitromethane 2

MPM para-Methoxy-benzylchloride

NBS N-bromosuccinimide

NIS N- Iodosuccinimide

NMR Nuclear magnetic resonance

NOESY Nuclear Overhauser effect spectroscopy

NaH Sodium hydride

NaBH Sodium borohydride 4
CN Sodium cyanoborohydride 3

Ph Phenyl

PMB p-Methoxybenzyl

PMBCl p-Methoxybenzylchloride

PhSK Potassium benzothionolate

PheSeK Potassium phenylselenate

Pd(Ph ) Tetra-kis phenyl palladium 3 4
) RhCl Tetra-kis tetraphenyl palladium rhodium chloride (Willkinson’s catalyst) 3 4

Pd(OH) Palladium (II) hydroxide 2

PhTh Phthaloyl

Rha Rhamnose

SnCl Tin(II) chloride 2

Tf Trifluoromethanesulphonyl


TfOH Trifluoromethane sulphonic acid

TFA Trifluoroacetic acid

TMS Trimethylsilyl

TMSOTf Trifluoromethanesulphonic acid trimethylsilylster

TOCSY Total correlation spectroscopy

Trt Trityl

Ts Tosyl

p-TsOH p-Toluosulphonic acid

Z Benzyloxycarbonyl