Elucidating mechanism of glycosylation reactions with computational methods

Glycosylation reaction is the central reaction for chemically constructing a manifold of biologically active molecules. An understanding of the mechanism of the glycosylation reaction promise to guide the rational design of glycosyl donors, acceptors, and addictive agents for accomplishing high ster...

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Main Author: Guo, Aoxin
Other Authors: Liu Xuewei
Format: Thesis-Doctor of Philosophy
Language:English
Published: Nanyang Technological University 2021
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Online Access:https://hdl.handle.net/10356/152273
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Institution: Nanyang Technological University
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spelling sg-ntu-dr.10356-1522732023-02-28T23:43:08Z Elucidating mechanism of glycosylation reactions with computational methods Guo, Aoxin Liu Xuewei School of Physical and Mathematical Sciences XueWei@ntu.edu.sg Science::Chemistry Glycosylation reaction is the central reaction for chemically constructing a manifold of biologically active molecules. An understanding of the mechanism of the glycosylation reaction promise to guide the rational design of glycosyl donors, acceptors, and addictive agents for accomplishing high stereo- and regio- selectivity, which has been keenly pursued by glycochemists for decades. With the striding developments in computer hardware, algorithm, physical theory, and numerical methods over the past decades, simulation of chemical systems comprising up to ~200 atoms, which encompass a large fraction of the experimentally synthesized organic molecules, with quantum mechanical (QM) theory, especially the density functional theory (DFT) based methods, could now be achieved on a practical timescale and cost, with satisfactory reliability and accuracy. DFT calculations enable predictions of the geometry structures, energies, and spectroscopic properties of the reagents, products, intermediates, and most importantly, transition states, which are not amenable to experimental characterizations with most of the routinely employed techniques and have become a powerful tool for rationalizing the reaction mechanism for organic reactions. Following a brief background introduction in Chapter 1, Chapter 2 presents a theoretical investigation on the mechanistic details giving rise to acceptor-dependent stereoselectivity of glycosylation by the 2-cynobenzyl glucose donor developed by Le Mai Huang and Liu. Then, Chapter 3 presents a novel phosphazene superbase catalyzed regio- and stereoselective glycosylation of alcohols by glycal donors, as well as the theoretical investigations on the mechanism of the reaction leading to the 4-position-substituent-dependent stereoselectivity and the regioselectivity. Finally, Chapter 4 presents the development of a novel alpha-selective glycal glycosylation reaction catalyzed by a simple iridium-metal catalyst, and the application of DFT theory calculations in elaborating the mechanisms giving rise to the alpha-stereoselectivity of the reactions. Doctor of Philosophy 2021-07-28T06:27:54Z 2021-07-28T06:27:54Z 2021 Thesis-Doctor of Philosophy Guo, A. (2021). Elucidating mechanism of glycosylation reactions with computational methods. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/152273 https://hdl.handle.net/10356/152273 10.32657/10356/152273 en This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
spellingShingle Science::Chemistry
Guo, Aoxin
Elucidating mechanism of glycosylation reactions with computational methods
description Glycosylation reaction is the central reaction for chemically constructing a manifold of biologically active molecules. An understanding of the mechanism of the glycosylation reaction promise to guide the rational design of glycosyl donors, acceptors, and addictive agents for accomplishing high stereo- and regio- selectivity, which has been keenly pursued by glycochemists for decades. With the striding developments in computer hardware, algorithm, physical theory, and numerical methods over the past decades, simulation of chemical systems comprising up to ~200 atoms, which encompass a large fraction of the experimentally synthesized organic molecules, with quantum mechanical (QM) theory, especially the density functional theory (DFT) based methods, could now be achieved on a practical timescale and cost, with satisfactory reliability and accuracy. DFT calculations enable predictions of the geometry structures, energies, and spectroscopic properties of the reagents, products, intermediates, and most importantly, transition states, which are not amenable to experimental characterizations with most of the routinely employed techniques and have become a powerful tool for rationalizing the reaction mechanism for organic reactions. Following a brief background introduction in Chapter 1, Chapter 2 presents a theoretical investigation on the mechanistic details giving rise to acceptor-dependent stereoselectivity of glycosylation by the 2-cynobenzyl glucose donor developed by Le Mai Huang and Liu. Then, Chapter 3 presents a novel phosphazene superbase catalyzed regio- and stereoselective glycosylation of alcohols by glycal donors, as well as the theoretical investigations on the mechanism of the reaction leading to the 4-position-substituent-dependent stereoselectivity and the regioselectivity. Finally, Chapter 4 presents the development of a novel alpha-selective glycal glycosylation reaction catalyzed by a simple iridium-metal catalyst, and the application of DFT theory calculations in elaborating the mechanisms giving rise to the alpha-stereoselectivity of the reactions.
author2 Liu Xuewei
author_facet Liu Xuewei
Guo, Aoxin
format Thesis-Doctor of Philosophy
author Guo, Aoxin
author_sort Guo, Aoxin
title Elucidating mechanism of glycosylation reactions with computational methods
title_short Elucidating mechanism of glycosylation reactions with computational methods
title_full Elucidating mechanism of glycosylation reactions with computational methods
title_fullStr Elucidating mechanism of glycosylation reactions with computational methods
title_full_unstemmed Elucidating mechanism of glycosylation reactions with computational methods
title_sort elucidating mechanism of glycosylation reactions with computational methods
publisher Nanyang Technological University
publishDate 2021
url https://hdl.handle.net/10356/152273
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