Expanding the Synthetic Library of C7 N-acetylneuraminic Acid Analogues
(2023) KEMR30 20231Department of Chemistry
- Abstract
- Sialic acids are prominent on the cell surfaces of mammalian cells and partake in modulating cellular mechanisms. N-acetyl neuraminic acid (Neu5Ac) is one of the most prominent sialic acids on mammalian cells. Bacterial pathogens can acquire Neu5Ac from the environment and display them on their cell surfaces, in a process known as molecular mimicry, thus evading the immune system. Many pathogens also utilize Neu5Ac for metabolic purposes.
Proteus mirabilis and Staphylococcus aureus are associated with a wide range of infectious diseases and they acquire Neu5Ac via a sialic acid transporter (SiaT). The SiaT of the two bacterial pathogens shares homology. Thus there is an interest in inhibiting the sialic acid transporter to suppress... (More) - Sialic acids are prominent on the cell surfaces of mammalian cells and partake in modulating cellular mechanisms. N-acetyl neuraminic acid (Neu5Ac) is one of the most prominent sialic acids on mammalian cells. Bacterial pathogens can acquire Neu5Ac from the environment and display them on their cell surfaces, in a process known as molecular mimicry, thus evading the immune system. Many pathogens also utilize Neu5Ac for metabolic purposes.
Proteus mirabilis and Staphylococcus aureus are associated with a wide range of infectious diseases and they acquire Neu5Ac via a sialic acid transporter (SiaT). The SiaT of the two bacterial pathogens shares homology. Thus there is an interest in inhibiting the sialic acid transporter to suppress bacterial growth. Previous work has focused on the modification of other positions of Neu5Ac.
In this thesis, the aim was to investigate different synthetic modifications on C7 of Neu5Ac. Neu5Ac is not a trivial carbohydrate, it possesses multiple functional groups such as a carboxylic acid, an acetamide, and a glycerol side chain. Hence protecting groups in the form of a methyl ester and a thioglycoside were employed to selectively convert the glycerol side chain to an aldehyde. The C7 aldehyde was then subjected to various reactions such as epoxidation, olefinations, and azide formation all with varying degrees of success. The deprotection of the thioglycoside was optimized by conducting the reaction in the absence of
light. (Less) - Popular Abstract
- Carbohydrates are an ambiguous group of molecules and are often associated with being either a vital or harmful source of nutrition. Contrary to popular belief, carbohydrates play a pivotal role in the defense system of our bodies. The outermost part of our cells is decorated with a dense layer of glycoconjugates that are important in modulating communication between the cell and the surrounding environment. The most prominent carbohydrate on the terminal position of the glycoconjugates is sialic acid. Sialic acids help the immune system differentiate between endogenous (self) and exogenous (other) substances. Bacterial pathogens can acquire sialic acids from the environment and decorate their cell surfaces with
it in a phenomenon known... (More) - Carbohydrates are an ambiguous group of molecules and are often associated with being either a vital or harmful source of nutrition. Contrary to popular belief, carbohydrates play a pivotal role in the defense system of our bodies. The outermost part of our cells is decorated with a dense layer of glycoconjugates that are important in modulating communication between the cell and the surrounding environment. The most prominent carbohydrate on the terminal position of the glycoconjugates is sialic acid. Sialic acids help the immune system differentiate between endogenous (self) and exogenous (other) substances. Bacterial pathogens can acquire sialic acids from the environment and decorate their cell surfaces with
it in a phenomenon known as ‘molecular mimicry’ thus disguising themselves as endogenous cells. This allows the pathogens to evade the immune system of the host.
According to WHO (the World Health Organization), the increase of antibiotic resistance amongst bacterial pathogens is a major threat as it is becoming more difficult to treat infectious diseases. Pathogens that use molecular mimicry can acquire sialic acids with the help of specific sialic acid transporters found in their cell membranes. The interest lies in inhibiting the specific transport proteins with a suitable sialic acid analog.
This thesis aimed to investigate possible synthetic modifications on one of the most prominent sialic acids in nature, N-acetylneuraminic acid (Neu5Ac). This carbohydrate consists of a nine-carbon backbone with different functional groups, rendering it challenging to work with. The main focus was to synthesize different analogs of Neu5Ac, with modifications on the seventh position. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9123425
- author
- Khwaja, Sakina LU
- supervisor
- organization
- course
- KEMR30 20231
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Carbohydrates, Neuraminic acid, Organic Chemistry, Sialic Acids
- language
- English
- id
- 9123425
- date added to LUP
- 2023-06-14 10:18:32
- date last changed
- 2023-06-14 10:18:32
@misc{9123425,
abstract = {{Sialic acids are prominent on the cell surfaces of mammalian cells and partake in modulating cellular mechanisms. N-acetyl neuraminic acid (Neu5Ac) is one of the most prominent sialic acids on mammalian cells. Bacterial pathogens can acquire Neu5Ac from the environment and display them on their cell surfaces, in a process known as molecular mimicry, thus evading the immune system. Many pathogens also utilize Neu5Ac for metabolic purposes.
Proteus mirabilis and Staphylococcus aureus are associated with a wide range of infectious diseases and they acquire Neu5Ac via a sialic acid transporter (SiaT). The SiaT of the two bacterial pathogens shares homology. Thus there is an interest in inhibiting the sialic acid transporter to suppress bacterial growth. Previous work has focused on the modification of other positions of Neu5Ac.
In this thesis, the aim was to investigate different synthetic modifications on C7 of Neu5Ac. Neu5Ac is not a trivial carbohydrate, it possesses multiple functional groups such as a carboxylic acid, an acetamide, and a glycerol side chain. Hence protecting groups in the form of a methyl ester and a thioglycoside were employed to selectively convert the glycerol side chain to an aldehyde. The C7 aldehyde was then subjected to various reactions such as epoxidation, olefinations, and azide formation all with varying degrees of success. The deprotection of the thioglycoside was optimized by conducting the reaction in the absence of
light.}},
author = {{Khwaja, Sakina}},
language = {{eng}},
note = {{Student Paper}},
title = {{Expanding the Synthetic Library of C7 N-acetylneuraminic Acid Analogues}},
year = {{2023}},
}