Enantioselective Synthesis of Functionalised Vinyl Sulfones

Files in This Item:
 File SizeFormat
Download103036191.pdf11.35 MBAdobe PDF
Title: Enantioselective Synthesis of Functionalised Vinyl Sulfones
Authors: Shen, Wen
Permanent link: http://hdl.handle.net/10197/13027
Date: 2022
Online since: 2022-08-02T14:14:34Z
Abstract: Peptidyl vinyl sulfones are a class of irreversible protease inhibitors due to their covalent bonding to a cysteine residue in the enzyme active site and have proven anti-trypanosomal activity. The traditional linear synthesis route is limited to commercially available single enantiomer precursors. Therefore, only the (S)-configuration vinyl sulfone can be formed and the range of substituents available is also limited. Presented herein is a new synthetic route to the vinyl-sulfone-based protease inhibitors. This new strategy features an enantioselective a-amination Horner-Wadsworth-Emmons reaction and the obtained enantioenriched N,N’-di-protected trans-[phenyl(sulfonyl)]vinyl hydrazine intermediates were successfully converted into both diastereomers of dipeptidyl vinyl sulfones. Chapter 1 introduces the chemistry and biology of vinyl sulfones. It briefly covers the background of cysteine proteases and specific bioactivity of cysteine proteases in parasites and viruses. Chapter 2 describes the attempts to synthesise peptide-based vinyl sulfones through an aminooxylation Horner-Wadsworth-Emmons reaction and the problematic reductions of the intermediate ¿-azido vinyl sulfones. Chapter 3 describes the development of an a-amination Horner-Wadsworth-Emmons featured synthetic route. The conversion of these ¿-hydrazino vinyl sulfones to the desired ¿-amino substituted compounds was achieved through a Boc-deprotection, Zn reduction, N-functionalisation sequence. This process enabled synthesis of the aimed dipeptide-based vinyl sulfones inhibitors, including the well-studied cysteine proteases inhibitor K11777 and its diastereomer. The deprotected enantioenriched vinyl sulfone hydrazinium salts in this sequence were also converted into the corresponding N-heterocycle vinyl sulfones. Chapter 4 includes the experimental details for Chapters 2 and 3 and an Appendix contains selected spectroscopic details.
Type of material: Doctoral Thesis
Publisher: University College Dublin. School of Chemistry
Qualification Name: Ph.D.
Copyright (published version): 2022 the Author
Keywords: Organic chemistryEnantioselective synthesisCysteine protease inhibitors
Language: en
Status of Item: Peer reviewed
This item is made available under a Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Appears in Collections:Chemistry Theses

Show full item record

Page view(s)

checked on Aug 14, 2022


checked on Aug 14, 2022

Google ScholarTM


If you are a publisher or author and have copyright concerns for any item, please email research.repository@ucd.ie and the item will be withdrawn immediately. The author or person responsible for depositing the article will be contacted within one business day.