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University of Groningen
Stereoselective synthesis of glycerol-based lipids
Fodran, Peter
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2015
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Download date: 10-08-2017
Stereoselective Synthesis of Glycerol-based
Lipids
Peter Fodran
1
The work described in this thesis was carried out at the Stratingh Institute for
Chemistry, University of Groningen, The Netherlands.
This work was financially supported by the Zernike Institute for Advanced Materials.
Printed by: Ipskamp Drukkers, Enschede
Cover design: Peter Fodran
Stereoselective Synthesis of
Glycerol-based Lipids
PhD thesis
to obtain the degree of PhD at the
University of Groningen
on the authority of the
Rector Magnificus Prof. E. Sterken
and in accordance with
the decision by the College of Deans
This thesis will be defended in public on
Friday 13th March 2015 at 12:45
By
Peter Fodran
born on 12th June 1985
in Bratislava, Slovak Republic
3
Supervisor
Prof. A. J. Minnaard
Assessment committee
Prof. M. H. Clausen
Prof. F. J. Dekker
Prof. J. G. Roelfes
How come it is not possible? People are flying to the moon and you want to tell me
that you cannot fix this (vacuum cleaner, stove, hairdryer…)?
(Iveta Fodranová)
5
CONTENTS
Chapter 1 An Introduction to Phospholipids
Introduction
Nomenclature
Biosynthesis
of
fatty
acids,
sphingolipids,
triacylglycerols,
glycerophospholipids
Biosynthesis of fatty acids
Biosynthesis of sphingolipids
Biosynthesis of triacylglycerols and glycerophospholipids
Biosynthesis of non-archaeal ether based lipids
Outline of this thesis
References and footnotes
Chapter 2 Synthesis of Methyl-branched Fatty Acids
Introduction
Tuberculostearic acid
Results and discussion
(R)-Tuberculostearic acid
Caspofungin fatty acid
Conclusions
Experimental part
References and footnotes
Chapter 3 Catalytic Synthesis of Enantiopure Mixed Diacylglycerols
Introduction
Results and discussion
Synthesis of enantiopure phospholipids
Enantiopurity does not decrease during the ring opening
Synthesis of the platelet-activating factor (PAF)
Conclusions
Experimental section
References and footnotes
Chapter 4 Enantiopure Triacylglycerols in Three Steps
Introduction
Reported syntheses of triacylglycerols
Results and discussion
Co[(R,R)-salen] catalyzed ring opening of glycidyl esters
Towards the automated synthesis of triacylglycerols
Conclusions
Experimental part
References and footnotes
1
2
4
and
6
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93
7
Chapter 5 A Methyl Matters
95
Introduction
96
Results and discussion
101
Chemical synthesis of the phospholipids
101
Formation of the liposomes and proteoliposomes
102
Molecular dynamics study of the bilayers
104
Calcein efflux assay
106
Conclusions and outlook
110
Experimental part
111
References and footnotes
121
Chapter 6 Synthesis of a Cyclooctyne–based Lipidation Probe
123
Introduction
124
Design of a lipophilic lipidation probe
127
Results and discussion
128
Conclusions and outlook
131
Experimental part
132
References
140
Chapter 7 A Missing Link in Archaeal Lipid Biosynthesis; a Contribution
from Organic Synthesis
143
Introduction
144
Biosynthesis of archaeal membrane lipids
145
Archaeal lipids as taxanomic markes
149
Results and discussion
149
Synthesis of 2,3-bis-O-(geranylgeranyl)-sn-glycero-1-phosphate
149
Identification of CDP-archaeol synthase
153
Catalytic alcoholysis of benzylglycidol as a key step in the synthesis of cycloarchaeol and -glucosyl-cyclo-archaeol
154
Conclusion
157
Experimental part
157
References and footnotes
167
Summary
171
Samenvatting
175
Acknowledgements
180