An excursion into the chemistry of N- and C-glycosides of D-galacturonic acid [Elektronische Ressource] / vorgelegt von Gnuni Karapetyan
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An excursion into the chemistry of N- and C-glycosides of D-galacturonic acid [Elektronische Ressource] / vorgelegt von Gnuni Karapetyan

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AN EXCURSION INTO THE CHEMISTRY OF N- AND C-GLYCOSIDES OF D-GALACTURONIC ACID DISSERTATION zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Rostock vorgelegt von Gnuni Karapetyan geb. am 08.09.1981 Rostock, April 2008 [urn:nbn:de:gbv:28-diss2008-0045-2] Dekan: Prof. Dr. Dieter Neßelmann Gutachter der Dissertation: 1. Prof. Dr. Christian Vogel 2. Prof. Dr. Udo Kragl Termin der mündlichen Prüfung: 21.05.2008 1. Prüfer: Prof. Dr. Christian Vogel (Hauptfach: Organische Chemie) 2. Prüfer: PD. Dr. Birgit Tiefenbach (Nebenfach: Toxikologie) Termin des wissenschaftlichen Kolloqiums: 03.06.2008 If you want to build a ship don’t herd people together to collect wood and don’t assign them tasks and work, but rather teach them to long for the endless immensity of the sea. Antoine-Marie-Roger de Saint-Exupery ___________________________________________________________________________ Preface The presented work in this dissertation was carried out from July 2005 till November 2007 at the Institute of Chemistry at the University of Rostock. I would like to thank my supervisor Prof. Dr. Christian Vogel, for his continuous support and insightful comments on my work. I have highly benefited from his scientific and personal experience. Prof.

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Published 01 January 2008
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AN EXCURSION INTO THE CHEMISTRY OF
N- AND C-GLYCOSIDES OF
D-GALACTURONIC ACID




DISSERTATION
zur
Erlangung des akademischen Grades
doctor rerum naturalium (Dr. rer. nat.)
der Mathematisch-Naturwissenschaftlichen Fakultät
der Universität Rostock




vorgelegt von
Gnuni Karapetyan
geb. am 08.09.1981



Rostock, April 2008


[urn:nbn:de:gbv:28-diss2008-0045-2]










Dekan: Prof. Dr. Dieter Neßelmann


Gutachter der Dissertation:
1. Prof. Dr. Christian Vogel
2. Prof. Dr. Udo Kragl


Termin der mündlichen Prüfung: 21.05.2008
1. Prüfer: Prof. Dr. Christian Vogel (Hauptfach: Organische Chemie)
2. Prüfer: PD. Dr. Birgit Tiefenbach (Nebenfach: Toxikologie)

Termin des wissenschaftlichen Kolloqiums: 03.06.2008













If you want to build a ship don’t herd people together to collect wood and don’t assign them
tasks and work, but rather teach them to long for the endless immensity of the sea.
Antoine-Marie-Roger de Saint-Exupery















___________________________________________________________________________
Preface

The presented work in this dissertation was carried out from July 2005 till November 2007 at
the Institute of Chemistry at the University of Rostock.
I would like to thank my supervisor Prof. Dr. Christian Vogel, for his continuous support and
insightful comments on my work. I have highly benefited from his scientific and personal
experience.
Prof. Dr. Otto Holst (Research Center Borstel, Leibniz Center for Medicine and Biosciences,
Germany) is greatly acknowledged for the excellent scientific and personal support that I
received during my stay in Borstel. The special thanks to all my colleges and friends from
Research Center Borstel for creating brilliant working atmosphere and for providing me with
the effective training. It was my great pleasure to be a part of international club
“Ausländerbande-Borstel”.
I would like to express my gratitude to Prof. Dr. Aida Avetisyan (Faculty of Chemistry,
Yerevan State University, Armenia) for her kind support.
Herbstreith & Fox and especially Dr. Hans-Ulrich Endress is acknowledged for financial
support. The analytical measurements in presented work were performed by analytical staff of
the Institute of Chemistry and Leibniz Institute for Catalysis at the University of Rostock. All
colleagues are gratefully acknowledged for their excellent cooperation. Among others my
special thanks to Prof. Helmut Reinke for X-ray studies, Dr. Roland Ruth and Dr. Christina
Fischer for MS measurements, Dr. Dirk Michalik, Brigitt Schimanski for NMR
measurements, Dr. Ursula Bentrup, Dr. Annegret Tillak and Angela Niemann for IR
measurements. Furthermore, I thank group members of Prof. Christian Vogel for a good
teamwork in the lab. I highly appreciate the hours of very interesting and motivating
discussions I had with Dr. Anahit Pews-Davtyan and Dr. Leonid Kononov. My very special
thanks to Dr. Man Kin Tse. This manuscript benefited greatly from his meticulous corrections.
Last but not least, I deeply indebted to my father, who regardless of the distance has always
been next to me, to Arevik, my wife, for her unconditional understanding and patience during
this thesis journey. A big thank you to all my friends spread all over the world. I am lucky and
happy that you all exist. You all give me a spiritual power for science and for life.

Gnuni Karapetyan
April 2008, Rostock
TABLE OF CONTENTS
Abbreviations i
1. Introduction........................................................................................................................ 1
1.1. The Plant Cell wall..................................................................................................... 1
1.2. Pectic Polysaccharides............................................................................................... 2
1.2.1. Composition and Structure................................................................................. 2
1.2.2. The Biological Activities ................................................................................... 4
1.2.3. Pectin in Human Diet. Natural Cation Exchanger ............................................. 5
1.2.4. Pectin in Cancer Research.................................................................................. 5
1.3. Objectives................................................................................................................... 7
2. Results & Discussion ......................................................................................................... 8
2.1. Synthesis of D-Galactopyranosyl Uronate N-Glycosides........................................... 8
2.1.1. Synthesis of Differently Protected D-Galactopyranosyl Uronate Azides as
Glycosamino Acid Precursors........................................................................... 8
2.1.2. Derivatisation of Azido Group......................................................................... 16
2.2. D-Galactopyranosyluronate C-Glycosides ............................................................... 20
2.2.1. Synthesis of β-D-Galactopyranosyluronate Cyanide (56)................................ 20
2.2.2. Synthesis of O-Acyl Protected C-Allyl α-D-Galactopyranuronates................. 23
2.2.3. C-Allyl α-D-Galactopyranuronates and Their Temperature Controlled
Benzoylation.................................................................................................... 31
2.2.4. Derivatisation of C-Allyl Group ...................................................................... 36
2. Summary.......................................................................................................................... 40
4. Experimental Section....................................................................................................... 46
4.1. General..................................................................................................................... 46
4.2. Synthesis of Differently Protected D-Galactopyranosyl Uronate Azides ................ 47
4.3. Derivatisation of Azido Group................................................................................. 67
4.4. Synthesis of β-D-Galactopyranosyruronate Cyanide (56)........................................ 74
4.5. Synthesis of O-Acyl Protected C-Allyl α-D-Galactopyranuronates......................... 77
4.6. O-Benzoyl Protected C-Allyl- α-D-Galyctopyranuronates: The Temperature
Controlled Benzoylation ...................................................................................................... 92
4.7. Derivatisation of C-Allyl Group ............................................................................ 102
5. References...................................................................................................................... 116
6. Appendix........................................................................................................................ 122 ABBREVIATIONS i
ABBREVIATIONS

1-HOBT 1-hydroxybenzotriazole
abs. absolute
Ac acetyl
All allyl
aq aqueous
ATR attenuated total reflection
Bz benzoyl
Bn benzyl
br. broud
calcd calculated
CI chemical ionization
COSY correlated spectroscopy
CP citrus pectin
dd doublet of doublets
ddd doublet of doublet of doublets
dddd doublet of doublet of doublet of doublets
dec. decomposition
DEPT distortionless enhancement by polarisation transfer
Dha 3-deoxy-D-lyxo-2-heptulosaric acid
DIPEA diisopropylethylamine
DM degree of methyl esterification
DMAP N,N’-dimethyl-4-aminopyridine
DMF N,N-dimethylformamide
DMSO dimethylsulfoxide
DNA deoxyribonucleic acid
dq doublet of quartets
dt doublet of triplets
dRG dimmer of rhamnogalacturonan
EDC 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
EI electron impact
ELISA enzyme linked immuno sorbent assay
ESI electrospray
Et ethyl
FAB fast atom bombardment
Fig. figure
GAA glycosylamino acid
GalA galacturonic acid
GalpA galactopyranuronic aicd
HG homogalacturonan
HMBC heteronuclear multiple bond correlation
HMPT hexamethylphosphoramide
HPLC high performance liquid chromatography
HRMS high-resolution mass spectroscopy
HSQC heteronuclear single quantum coherence
Hz hertz
IR Infrared spectroscopy
Kdo 2-keto-3-deoxy-D-manno-octulosonic acid
LC-MS coupled liquid chromatography-mass spectroscopy ABBREVIATIONS ii
lit. literature
m multiplet
mAb monoclonal antibody
MCP modified citrus pectin
Me methyl
MHz megahertz
mp melting point
MPLC medium pressure liquid chromatography
MS Mass spectroscopy
MS 4Å molecular siev 4 angstrem
m/z mass to charge ratio
ND not determined
NMR Nuclear magnetic resonance (spectroscopy)
NOESY nuclear overhauser effect spectroscopy
pD pondus deutorii
PG polygalacturonase
pH pondus hydrogenii
Ph phenyl
PME pectin methyl esterase
q quartet
ref. referenced
R organic moiety, rest
R retention factor f
RG rhamnogalacturonan
RP reversed phase
r.t. room temperature
s singlet
SAA sugar amino acid
t triplet
TEMPO 2,2,6,6-tetramethylpiperidine-1-oxyl
THF tetrahydrofuran
TLC thin layer chromatography
Trt trityl
XGA xylogalacturonan
[α] optical rotation
δ chemical shift