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Efficient synthesis of phospholipids from glycidyl phosphates
Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology.
Linköping University, The Institute of Technology. Linköping University, Department of Physics, Chemistry and Biology, Organic Chemistry .
2002 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 67, no 1, p. 194-199Article in journal (Refereed) Published
Abstract [en]

New efficient routes to enantiopure phospholipids, starting from (S)-glycidol, are described. Lysophosphatidic acids and phosphatidic acids were obtained in good overall yields from (S)-glycidol, in only three and four steps, respectively. Moreover, the strategy can also be used to produce phosphatidylcholines in three steps. Using dialkylphosphoramidites, (S)-glycidol was phosphorylated to give (R)-1-O-glycidyl dialkyl phosphates. Regiospecific epoxide opening, using hexadecanol or cesium palmitate, followed by phosphate deprotection, provided lysophosphatidic acids. 2-O-Esterification prior to phosphate deprotection provided 1,2-O-diacyl and 1-O-alkyl-2-O-acyl phosphatidic acids. Phosphorylation of (S)-glycidol using phosphorus oxychloride followed by in situ treatment with choline tosylate produced (R)-glycidyl phosphocholine. Subsequent nucleophilic opening of the epoxide using cesium palmitate produced 1-O palmitoyl-sn-glycero-3-phosphocholine, which has been used in syntheses of phosphatidylcholines.

Place, publisher, year, edition, pages
2002. Vol. 67, no 1, p. 194-199
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-47127DOI: 10.1021/jo010734+OAI: oai:DiVA.org:liu-47127DiVA, id: diva2:268023
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2021-10-01
In thesis
1. Phosphorylated Monomolecular Layers: Design, Synthesis, Characterization and Application
Open this publication in new window or tab >>Phosphorylated Monomolecular Layers: Design, Synthesis, Characterization and Application
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the design, synthesis and characterization of organo-phosphatemonomolecular layers, so called self-assembled monolayers, using the strategy of linking organosulfur substances to a gold surface. Moreover there is also a paper included, which describes the development of synthetic pathways to various phospholipids, for which I have developed an interest in later projects.

For the first study of the properties of phosphates, and also for concomitant application of developed systems, analogues of the amino acids serine, threonine and tyrosine, phosphorylated and non-phosphorylated, were synthesized. 16-Mercaptohexadecanamide based analogues were characterized as monolayers and large polar and charge effects were observed, introduced by the phosphate. Problems were, however, encountered as a post modification of phosphates was applied and a disordering of the monolayers observed. Moreover there were no expected effects observable upon interaction with Ca2+ and Mg2+.

Based on the conclusions from the first study 3-mercaptopropionamide based analogues were used instead. Characterization of the analogues including counter ion exchange (H+,Na+, Ca2+ and Mg2+) revealed large electronic and possible structural differences depending on the counter ion.

Again the charge and polar effects induced by the phosphate were investigated, and the study was also extended to interaction of the phosphate with Ca2+ and Mg2+. Strong effects were observed, which were also dependent on the ion concentration within a significant range. The polarity and charge properties of the phosphate layer were thus found to be variable.

In the fourth study an additional Ca2+ and Mg2+ sensitive system was applied in combination with the phosphate surface. Phosphate surface/phospholipid vesicle interactions were studied under different conditions of Mg2+ (Ca2+) treatment. For comparison, the corresponding hydroxyl and sulphate surfaces were included and also the most well characterized surface concerning phospholipid vesicle interaction, SiO2. Most importantly, supported phospholipid bilayer (SPB) formation was found to be inducible on both the phosphate and sulphate surfaces, however at defined conditions of Mg2+ (Ca2+) treatment and concentration. The conclusion is that the processes of phospholipid vesicle adsorption and SPB formation are largely dependent on vesicle/surface interaction and vesicle stability.

The last paper included in this thesis is a synthetic method development aimed at easy preparations of various phospholipid derivatives. In the future these methods could be used for synthesis of functionalized lipids and aid in the development of models mimicking biological systems such as artificial cell membranes.

Place, publisher, year, edition, pages
Linköping: Linköping University, 2002. p. 51
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 764
National Category
Physical Chemistry
Identifiers
urn:nbn:se:liu:diva-179557 (URN)9173733954 (ISBN)
Public defence
2002-09-27, hörsal Planck, Fysikhuset,, Linköpings Universitet, Linköping, 13:00
Opponent
Available from: 2021-09-24 Created: 2021-09-24 Last updated: 2023-03-07Bibliographically approved
2. Synthesis and Development of Methods for Preparation of Inositolphosphoglycans, Glycoglycerolipids and Glycerophospholipids
Open this publication in new window or tab >>Synthesis and Development of Methods for Preparation of Inositolphosphoglycans, Glycoglycerolipids and Glycerophospholipids
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the synthesis of a series of myo-inositol-containing oligosaccharides, and the exploration of using the chiral epoxide (S)-glycidol in short synthetic routes to glycoglycerolipids and glycerophospholipids.

In chapter 2, synthesis of the core heptasaccharyl myo-inositol Galp(α1-6)Galp(α1 -3)Galf(β1-3)[Glcp(α1-P04-6)Manp](α1-3)Manp(α1-4)GlcNp(α1-6)Ins-1-P04, found in the lipophosphoglycans of Leishmania parasites, is described. This part primarily deals with problematic deprotections of complex carbohydrates. In this context, the stability of anomeric phosphodiesters towards hydrolytic cleavage was studied.

In chapter 3, a short synthetic route to protected derivatives of 2-amino-2-deoxy-α-D-glucopyranosyl-(1➔6)-D-myo-inositol is presented. These derivatives are key building blocks in the synthesis of inositolphosphoglycans (IPGs) and glycosylphosphatidylinositol (GPI)-anchors.The building blocks were subsequently used for synthesis of IPGs, analogous to putative second messengers to insulin, to provide a small targeted library of compounds. A thiol-terminated spacer was introduced by radical elongation of allyl ethers with benzyl mercaptan, for immobilization of the IPGs by coupling to maleimide-functionalized solid phases, proteins or various probes. The aim of this project was to provide IPGs for evaluation of biological activity, isolation of antibodies, and identification of receptors for the second messengers to insulin.

Chapters 4 and 5 describe syntheses of galactoglycerolipids and glycerophospholipids via glycosylation or phosphorylation of the three-carbon synthon (S)-glycidol. Using this approach, three galactoglycerolipids and the corresponding glycerolipid were synthesized and an oxidation-reduction procedure for tritiation of the glycerolipid was developed. Two of the galactolipids have recently been identified in the human colon carcinoma cell line HT29. The synthetic method developed for the galactolipids was subsequently used to explore a new efficient route to enantiomerically pure glycerophospholipids. Lysophosphatidic acids and phosphatidic acids were obtained in good overall yields from (S)-glycidol, in only three and four steps, respectively. Moreover, a strategy for synthesis of lysophosphatidylcholines, in only three steps, is also described.

Place, publisher, year, edition, pages
Linköping: Linköping University, 2002. p. 59
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 770
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-179768 (URN)9173734209 (ISBN)
Public defence
2002-09-13, Planck, Fysikhuset, Linköpings Universitet, Linköping, 13:15
Opponent
Note

All or some of the partial works included in the dissertation are not registered in DIVA and therefore not linked in this post.

Available from: 2021-10-01 Created: 2021-10-01 Last updated: 2023-03-07Bibliographically approved

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Lindberg, JanEkeroth, JohanKonradsson, Peter

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