Solution and solid phase synthesis of N, N-̓diacetyl chitotetraoses [Elektronische Ressource] / von Balakumar Vijayakrishnan

Balakumar Vijayakrishnan

Informations

• Publié par: universitat_potsdam
• Publié le: 01 janvier 2008
• Nombre de lectures: 8
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

Institut für Chemie
Arbeitsgruppe Naturstoffchemie





Solution and solid phase synthesis of N,N’-diacetyl chitotetraoses









Dissertation
zur Erlangung des akademischen Grades
"doctor rerum naturalium"
(Dr. rer. nat.)
in der Wissenchaftsdisziplin ORGANISCHE CHEMIE







eingereicht an der
Mathematisch-Naturwissenschaflichen Fakultät
der Universität Potsdam



von
Balakumar Vijayakrishnan
aus Trichy, Indien


Potsdam, April 2008



This work is licensed under a Creative Commons License:
Attribution - Noncommercial - Share Alike 3.0 Unported
To view a copy of this license visit
http://creativecommons.org/licenses/by-nc-nd/3.0/










































Online published at the
Institutional Repository of the Potsdam University:
http://opus.kobv.de/ubp/volltexte/2008/1883/
urn:nbn:de:kobv:517-opus-18830
[http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-18830]

Die vorliegende Arbeit enstand in der Zeit Von September 2004 bis Dezember 2007 am
Institut für Chemie an der Universität Potsdam unter der Leitung Von Herren Prof. Dr. Martin
G. Peter.


























Gutachter: Prof. Dr. Martin G. Peter, Universität Potsdam
Prof. Dr. Bernd Schmidt, Universität Potsdam
Prof. Dr. Thomas Ziegler, Universität Tübingen


Tag der Disputation: 11 June 2008






















dedicated to my amma, appa, and anna

















Acknowledgement


I take this opportunity to express my heartfelt gratitude to my supervisor Prof. Dr. Martin G.
Peter for giving me this opportunity to work in his research group. I would like to thank for
his constant encouragement during the odd times, discussions and the freedom he gave me
throughout the research work. With out his help, this thesis could not be made.

I would like to thank Prof. Dr. Bernd Schmidt, Prof. Dr. Thomas Ziegler and Prof. Dr. Jürgen
Liebscher for agreeing to be my thesis reviewer.

I thank Dr. Michael Sefkow for the valuable discussions especially the experimental setup for
solid-phase synthesis and also his kind support.

I thank Dr. Haebel for teaching me to handle the MALDI-TOF machine and allow me to use
it according to my convenience.

I thank Dr. Heydenreich and Frau. Krtitschka for measuring the NMR data and also for the
discussions.

I thank Dr. Starke and Frau. Fürstenberg for measuring the ESI MS and Frau. Hannemann for
measuring the IR and Elemental analysis.

I would like to thank my colleague Dr. Arisara Issaree for the nice friendship. I thank all the
past members of Prof. Peter for their friendship and support during my stay. I would like to
thank the present members stephan, matthias and ericcson for the nice companionship. I
would like to thank Frau. Patzelt and Frau. Bastian for their administrative help. I would like
to thank the graduate students and diploma students working in the Department of Chemistry,
University of Potsdam for their timely help on various issues.

I would like to thank IMPRS on biomimetic systems for providing the scholarship and a
special thanks goes to the coordinator Dr. Angelo Valleriani.
I would like to thank Prof. S. Baskaran, IIT-Madras, Chennai, for his encouragement and I
thank Dr. Ganapati reddy, Dr. Kishore Kumar, Mr. A. Aravind and Dr. S.K. Mohanty for their
help during the initial stages of my research career.

I thank raj, lakshmanan, priya, sajani, vinod, raveendra, chitra, neha, padhu, tijo, paruthi,
nambi, umesh, sunil and arun for their wonderful company and support during my stay in
germany. I would like to thank manju, naren and karan for their friendship and kind support.

I also would like to thank my classmates sathish, tk, venkat, subbu, hari, bharathwaj, vbr,
balu, murali and durai for their nice company.

For above all, I would like to thank my father, mother and brother for their unconditional love
and moral support throughout these years.




















Abstract - German

Synthese von N,N’-Diacetylchitotetraosen in Lösung und an Fester Phase


Die drei wichtigsten Biopolymere sind Proteine, Nukleinsäuren und Glykokonjugate. Sie sind
von fundamentaler Bedeutung für lebenswichtige Prozesse, wie z.B. den Informationstransfer.
Die biologische Bedeutung von Proteinen und Nukleinsäuren ist eingehend erforscht,
während Oligosaccharide in Form von Glykokonjugaten erst in neuerer Zeit an Bedeutung
gewonnen haben. Die β-(1 →4) verknüpfte N-Acetylglucosamin (GlcNAc) Einheit kommt
häufig als in vielen natürlichen und biologisch wichtigen Oligosacchariden und ihren
Konjugaten vor. Chitin, ein Polymer von GlcNAc, ist in der Natur weit verbreitet, während
das verwandte Polysaccharid Chitosan (Polymer of GlcN und GlcNAc) in gewissen Pilzen
auftritt. Chitooligosaccharide gemischter Acetylierungsmuster sind von Bedeutung für die
Bestimmung von Substratwirkungen und für den Mechanismus von Chitinasen. In dieser
Arbeit beschreiben wir die chemische Synthese von drei Chitotetraosen, nämlich GlcNAc-
GlcN-GlcNAc-GlcN, GlcN-GlcNAc-GlcNAc-GlcN and GlcN-GlcN-GlcNAc-GlcNAc.
Benzyloxycarbonyl (Z) und p-Nitrobenzyloxycarbonyl (PNZ) wurden aufgrund ihrer
Fähigkeit, die β-Verknüpfung während der Glykosylierung durch die
Nachbargruppenbeteiligung zu steuern, als Aminoschutzgruppen verwendet. Zur Aktivierung
der Donoren wurde die Trichloracetamidat Methode angewendet. Monomere und dimere
Akzeptoren und Donoren wurden unter Verwendung von Z und PNZ Gruppen hergestellt. Die
Kupplung von geeigneten Donoren und Akzeptoren in Gegenwart einer Lewis Säure ergaben
die Tetrasaccharide. Schließlich ergab die Entschützung von PNZ, gefolgt von der
Reacetylierung der Aminogruppe und Abspalten der übrigen Schutzgruppen die N,N’-
Diacetylchitotetraosen in guten Ausbeuten. Weiterhin wird die erfolgreiche Synthese der
geschützten Diacetylchitotetraosen durch Festphasensynthese beschrieben.

Schlüsselwörter: Chitooligosaccaride, Chemische Synthese, Festphasensynthese,
Glykosylierung.






Abstract

Solution and solid phase synthesis of N,N’-diacetyl chitotetraoses

The three major biopolymers, proteins, nucleic acids and glycoconjugates are mainly
responsible for the information transfer, which is a fundamental process of life. The biological
importance of proteins and nucleic acids are well explored and oligosaccharides in the form of
glycoconjugates have gained importance recently. The β-(1 →4) linked N-acetylglucosamine
(GlcNAc) moiety is a frequently occurring structural unit in various naturally and biologically
important oligosaccharides and related conjugates. Chitin which is the most abundant polymer
of GlcNAc is widely distributed in nature whereas the related polysaccharide chitosan
(polymer of GlcN and GlcNAc) occurs in certain fungi. Chitooligosaccharides of mixed
acetylation patterns are of interest for the determination of the substrate specificities and
mechanism of chitinases. In this report, we describe the chemical synthesis of three
chitotetraoses namely GlcNAc-GlcN-GlcNAc-GlcN, GlcN-GlcNAc-GlcNAc-GlcN and
GlcN-GlcN-GlcNAc-GlcNAc.
Benzyloxycarbonyl (Z) and p-nitrobenzyloxycarbonyl (PNZ) were used for the amino
functionality due to their ability to form the β-linkage during the glycosylation reactions
through neighboring group participation and the trichloroacetimidate approach was utilized
for the donor. Monomeric, dimeric acceptors and donors have been prepared by utilizing the
Z and PNZ groups and coupling between the appropriate donor and acceptors in the presence
of Lewis acid yielded the protected tetrasaccharides. Finally cleavage of PNZ followed by
reacetylation and the deblocking of other protecting groups afforded the N,N’-diacetyl
chitotetraoses in good yield. Successful syntheses for the protected diacetyl chitotetraoses by
solid phase synthesis have also been described.

Keywords: Chitooligosaccharides, Chemical synthesis, Solution phase synthesis, Solid phase
synthesis, Glycosylation.






Contents


1 Introduction


1.