Glycosylation of Amino Acids and Efficient Synthesis of Glycosphingolipids

68 Pages·2015·3.1 MB·English

Georgia State University
ScholarWorks @ Georgia State University
Chemistry Theses Department of Chemistry
8-11-2015
Glycosylation of Amino Acids and Efficient
Synthesis of Glycosphingolipids
Jonathan Wooten
Georgia State University
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Recommended Citation
Wooten, Jonathan, "Glycosylation of Amino Acids and Efficient Synthesis of Glycosphingolipids." Thesis, Georgia State University,
2015.
http://scholarworks.gsu.edu/chemistry_theses/74
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GLYCOSYLATION OF AMINO ACIDS AND EFFICIENT SYNTHESIS OF
GLYCOSPHINGOLIPIDS

by

JONATHAN VALENTINE WOOTEN

Under the Direction of Peng George Wang, PhD

ABSTRACT
Glycoscience is an emerging field of science that focuses on the study of the structure,
biosynthesis, biology, and evolution of saccharides (sugars). It covers a broad range of subjects
including microwave-assisted synthesis as well as sphingolipid synthesis. In this field,
knowledge is limited due to the complexity of carbohydrates and their derivatives. Therefore, it
is all the more important that synthesis of these complex molecules occurs in order to fully
understand their biological significance. The following report summarizes two aspects of
glycoscience and discusses their biological applications.

INDEX WORDS: Microwave-assisted synthesis, Peracetylation, Diazotransfer reagent,
Glycoconjugate
GLYCOSYLATION OF AMINO ACIDS AND EFFICIENT SYNTHESIS OF
GLYCOSPHINGOLIPIDS

by

JONATHAN VALENTINE WOOTEN

A Thesis Submitted in Partial Fulfillment of the Requirements for the Degree of
Masters of Science Degree
in the College of Arts and Sciences
Georgia State University
2015
Copyright by
Jonathan Valentine Wooten
2015
GLYCOSYLATION OF AMINO ACIDS AND EFFICIENT SYNTHESIS OF
GLYCOSPHINGOLIPIDS

by

JONATHAN VALENTINE WOOTEN

Committee Chair: Peng George Wang

Committee: Maged Henary
Gangli Wang
Peng George Wang

Electronic Version Approved:

Office of Graduate Studies
College of Arts and Sciences
Georgia State University
August 2015
iv

DEDICATION
I dedicate this thesis to my family and my friends.
v

ACKNOWLEDGEMENTS
I would like to extend thanks and gratitude to my committee chairman and major advisor,
Dr. Peng G. Wang. Without his guidance, this work would not have been possible. Thanks are
also due to my supervisory mentor Dr. Yunpeng Liu and committee members, Dr. Maged
Heanry and Dr. Gangli Wang, for all of their help and guidance in completion of this research.
The support of my friends: Kristina Gardner, Zaikuan Yu, and Shukkoor Kondengaden
was invaluable in the completion of this project. In conclusion, I would like to thank my parents,
Joe and Karen Wooten, for always giving me support and love throughout my lifelong
endeavors.
1
TABLE OF CONTENTS
ACKNOWLEDGEMENTS ............................................................................................. v
LIST OF TABLES ............................................................................................................ 4
LIST OF FIGURES .......................................................................................................... 5
1 Comparison of Conventional and Microwave-assisted Synthesis of Glycosylated
Amino Acids .................................................................................................................................. 7
1.1 Introduction ......................................................................................................... 7
1.1.1 9 common sugars .......................................................................................... 10
1.2 Purpose of the Study ......................................................................................... 10
1.3 Expected Results ................................................................................................ 13
1.3.1 Scheme of O-Mannose attached Fmoc-serine (microwave) ....................... 13
1.3.3 Scheme O-Mannose attached Fmoc-Threonine (microwave) .................... 13
1.3.4 Scheme of O-Mannose attached Fmoc-serine (conventional) .................... 14
1.3.5 Scheme of O-Mannose attached Fmoc-Threonine (conventional)............. 14
1.4 EXPERIMENT .................................................................................................. 15
1.4.1 Microwave-assisted synthesis of Glycosylated Serine and Theronine. ....... 15
1.4.2 Mechanism of Fmoc-serine synthesis .......................................................... 15
1.4.3 Conventional synthesis of Glycosylated Serine and Threonine .................. 16
1.5 RESULTS ........................................................................................................... 17
1.5.1 Proton NMR Glycosylated Serine-microwave ............................................. 17
2
1.5.2 Carbon NMR Glycosylated Serine-microwave ............................................ 18
1.5.3 Mass Spectrometry (ESI) Glycosylated Serine-microwave ......................... 18
1.5.4 Proton NMR Glycosylated Serine-conventional .......................................... 19
1.5.5 Carbon NMR Glycosylated Serine-conventional ......................................... 19
1.5.6 Table. Microwave Reaction conditions ....................................................... 20
1.6 DISCUSSION .................................................................................................... 21
1.7 CONCLUSION .................................................................................................. 22
2 Efficient synthesis of glycosphingolipids using N-phenyltrifluoroacetimidates as
a leaving group ............................................................................................................................ 23
2.1 INTRODUCTION ............................................................................................. 23
2.1.1 Figure 12: Biosynthesis of a sphingolipid ................................................... 24
2.2 Purpose of Study ............................................................................................... 26
2.3 Expected Results ................................................................................................ 29
2.4 Experiment ......................................................................................................... 29
2.4.1 Synthesis of azidosphingosine ...................................................................... 29
2.4.2 Figure 17: Synthesis of azidosphingosine.................................................... 30
2.4.3 Synthesis of Diazotransfer reagent 1—Trifluoromethanesulfonyl azide
(TfN3) 30
2.4.4 Synthesis of Diazotrasnfer reagent 2—Imidazole-1-sulfonyl Azide ........... 31
2.4.5 Synthesis of a Glycosphingolipid .................................................................. 31
3
2.4.6 Figure 18: Final synthesis of azidosphingosine (1), preparation of the
glycosyl donor (2). Glycosylation of azidosphingosine (3) .................................................. 32
2.5 Results ................................................................................................................ 32
2.6 DISCUSSION .................................................................................................... 33
2.6.1 Figure 19: Comparison of TfN3 and Imidazole-1-sulfonyl Azide ............... 34
2.6.2 Figure 20: Synthetic Scheme of Imidazole-1-sulfonyl Azide ...................... 35
2.7 CONCLUSION .................................................................................................. 36
REFERENCES ................................................................................................................ 37
APPENDICES ................................................................................................................ 43
Appendix A .................................................................................................................. 43
Appendix B .................................................................................................................. 45