Synthesis and biological evaluation of rare monosaccharides and their mimics

Liu, Z

Abstract:: This thesis describes work in the synthesis and biological evaluation of different carbohydrates and their derivatives.

Azetidine carboxylic acid (Aze), as a pharmacophore in medicinal chemistry, is attracting more and more researchers in recent years. As a four membered ring analogue of proline, this nature occurring compound can be mis-incorporated into proteins and can cause changes in protein conformation and therefore induce toxic effects. It is therefore useful to study how...
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APA Style

Liu, Z. (2016). Synthesis and biological evaluation of rare monosaccharides and their mimics [PhD thesis]. University of Oxford.

MLA Style

Liu, Z. Synthesis and Biological Evaluation of Rare Monosaccharides and Their Mimics. 2016. University of Oxford, PhD thesis.

Chicago Style

Liu, Z. 2016. “Synthesis and Biological Evaluation of Rare Monosaccharides and Their Mimics.” PhD thesis, University of Oxford.
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Files:: Zilei Liu_Thesis_final.pdf

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Authors

+ Liu, Z More by this author

Division:: MSD
Department:: Biochemistry
Role:: Author

Contributors

+ Fleet, G

Role:: Supervisor

+ Wormald, M

Role:: Supervisor

DOI:: 10.5287/ora-nrx2k5vej
Type of award:: DPhil
Level of award:: Doctoral
Awarding institution:: University of Oxford

Language:: English
Keywords:: Azetidine Carboxylic Acid

Rhamnose operon

Rare Sugar

Iminosugar

Rhamnose
Subjects:: Glycobiology

Carbohydrate Chemistry
UUID:: uuid:bc101d4a-f19b-4a2e-816c-fa7db7936a6d
Deposit date:: 2016-07-21
ARK identifier:: ark:/29072/ora_bc101d4af19b4a2e816cfa7db7936a6d

Related item:: 3‐Fluoroazetidinecarboxylic Acids and trans,trans-3,4-Difluoroproline as Peptide Scaffolds: Inhibition of Pancreatic Cancer Cell Growth by a Fluoroazetidine Iminosugar
Description:: Reverse aldol opening renders amides of 3-hydroxyazetidinecarboxylic acids (3-OH-Aze) unstable above pH 8. Aze, found in sugar beet, is mis-incorporated for proline in peptides in humans and is associated with multiple sclerosis and teratogenesis. Aze-containing peptides may be oxygenated by prolyl hydroxylases resulting in potential damage of the protein by a reverse aldol of the hydroxyazetidine; this, rather than changes in conformation, may account for the deleterious effects of Aze. This paper describes the synthesis of 3-fluoro-Aze amino acids as hydroxy-Aze analogues which are not susceptible to aldol cleavage. 4-(Azidomethyl)-3-fluoro-Aze and 3,4-difluoroproline are new peptide building blocks. trans,trans-2,4-Dihydroxy- 3-fluoroazetidine, an iminosugar, inhibits the growth of pancreatic cancer cells to a similar degree as gemcitabine.
Related item:: L‐Fucose from Vitamin C with Only Acetonide Protection
Description:: Addition of human milk oligosaccharides (HMO) to baby foods may protect infants from disease. As many simple HMOs are fucosylated this is likely to increase the demand for L-fucose as a synthetic building block. Any chemical synthesis must be cheap to compete with a biotechnological process. Acetonide is the only protecting group we have used in this new synthesis of L-fucose from vitamin C in 27% overall yield (purification by recrystallization; no chromatography required in the entire sequence).
Related item:: Short and Sweet: d-Glucose to l-Glucose and l-Glucuronic Acid
Description:: The scarcity and expense of access to l-sugars and other rare sugars have prevented the exploitation of their biological potential; for example d-psicose, only recently available, has been recognized as an important new food. Here we give the definitive and cheap synthesis of 99.4% pure l-glucose from d-glucose which requires purification of neither intermediates nor final product other than extraction into and removal of solvents; a simple crystallization will raise the purity to > 99.8%.

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Copyright holder:: Liu, Z; Zilei Liu.

Licence:: Terms and Conditions of Use for Oxford University Research Archive

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Synthesis and biological evaluation of rare monosaccharides and their mimics

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Synthesis and biological evaluation of rare monosaccharides and their mimics

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