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Exploring Regioselective 5N-acylation of Neuraminic acid

Lilje, Simon Hans LU (2022) KEMP20 20222
Department of Chemistry
Abstract
In this project, a regioselective method to deprotect and acylate the amide on C5 of sialic acid
is explored. Sialic acid is one of the most complex monosaccharides and is an important ligand
in many higher organisms in intercellular cell communication. The most prominent example is
related to the immune system. Sialic acids are attached as the terminal carbohydrate on cell
surface glycans, which is one of the unique patterns, used to distinguish between enemy and
friend. Most pathogens need to take up sialic acid from their host, either to use it as an additional
energy source or to incorporate it in their cell surface glycans to mimic the host cells. This
mechanism leading to disguise is called molecular mimicry. The long-term aim... (More)
In this project, a regioselective method to deprotect and acylate the amide on C5 of sialic acid
is explored. Sialic acid is one of the most complex monosaccharides and is an important ligand
in many higher organisms in intercellular cell communication. The most prominent example is
related to the immune system. Sialic acids are attached as the terminal carbohydrate on cell
surface glycans, which is one of the unique patterns, used to distinguish between enemy and
friend. Most pathogens need to take up sialic acid from their host, either to use it as an additional
energy source or to incorporate it in their cell surface glycans to mimic the host cells. This
mechanism leading to disguise is called molecular mimicry. The long-term aim is to find sialic
acid derivatives to clog the transporters of the pathogens, resulting in a better immune response.
Synthesising derivatives of sialic acid isn’t trivial due to its carboxylic acid function next to the
anomeric hydroxyl group, four additional hydroxyl groups and an amide. This multitude of
functional groups requires elaborate protection group strategies, which make it possible to
address functional groups regioselectively. The simplest protecting strategy for sialic acid is the
esterification of the carboxylic acid and per acetylation of all the hydroxyl groups. The problem
was to remove just one of these acetyl groups. The new method, which is explored in this project
enables the removal of the acetamide from C5 of sialic acid, enabling an easy and fast amidation
of C5, saving four steps compared to the current synthetic pathway. However, side reactions
made the synthesis of new compounds more difficult than expected, so just a few new
compounds were observed in NMR and three were isolated. All in all, the reaction conditions,
especially for the amidation and the processing of the reactions have to be optimized before
simple synthesis is possible via this route. (Less)
Please use this url to cite or link to this publication:
author
Lilje, Simon Hans LU
supervisor
organization
course
KEMP20 20222
year
type
H2 - Master's Degree (Two Years)
subject
keywords
acylation, amide, antibacterial drugs, regioselective deprotection, sialic acid, organic chemistry
language
English
id
9102688
date added to LUP
2022-11-04 10:53:13
date last changed
2022-11-04 10:53:13
@misc{9102688,
  abstract     = {{In this project, a regioselective method to deprotect and acylate the amide on C5 of sialic acid
is explored. Sialic acid is one of the most complex monosaccharides and is an important ligand
in many higher organisms in intercellular cell communication. The most prominent example is
related to the immune system. Sialic acids are attached as the terminal carbohydrate on cell
surface glycans, which is one of the unique patterns, used to distinguish between enemy and
friend. Most pathogens need to take up sialic acid from their host, either to use it as an additional
energy source or to incorporate it in their cell surface glycans to mimic the host cells. This
mechanism leading to disguise is called molecular mimicry. The long-term aim is to find sialic
acid derivatives to clog the transporters of the pathogens, resulting in a better immune response.
Synthesising derivatives of sialic acid isn’t trivial due to its carboxylic acid function next to the
anomeric hydroxyl group, four additional hydroxyl groups and an amide. This multitude of
functional groups requires elaborate protection group strategies, which make it possible to
address functional groups regioselectively. The simplest protecting strategy for sialic acid is the
esterification of the carboxylic acid and per acetylation of all the hydroxyl groups. The problem
was to remove just one of these acetyl groups. The new method, which is explored in this project
enables the removal of the acetamide from C5 of sialic acid, enabling an easy and fast amidation
of C5, saving four steps compared to the current synthetic pathway. However, side reactions
made the synthesis of new compounds more difficult than expected, so just a few new
compounds were observed in NMR and three were isolated. All in all, the reaction conditions,
especially for the amidation and the processing of the reactions have to be optimized before
simple synthesis is possible via this route.}},
  author       = {{Lilje, Simon Hans}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Exploring Regioselective 5N-acylation of Neuraminic acid}},
  year         = {{2022}},
}