eprintid: 1446184
rev_number: 8
eprint_status: archive
userid: 636
dir: disk0/01/44/61/84
datestamp: 2017-07-24 10:02:12
lastmod: 2017-07-24 10:02:12
status_changed: 2017-07-24 10:02:12
type: thesis
metadata_visibility: show
item_issues_count: 0
creators_name: Walters, M
title: Synthesis of A83586C/citropeptin hybrid and synthetic studies toward azinothricin
ispublished: unpub
note: Thesis digitised by ProQuest.
abstract: The Azinothricin family of cyclodepsipeptides are a class of antitumour antibiotics whose antitumour properties are attributed to their ability to selectively repress the expression of genes essential for the progression of the cell cycle from G1 to S phase. They have been shown to inhibit E2F transcription factors, which are critical regulators of mammalian cellular proliferation. This biological observation has made them a potentially important new therapeutic target for the control of proliferative diseases, such as cancer. An asymmetric total synthesis of an A83586C-citropeptin hybrid is presented in this thesis, along with a synthetic route to the azinothricin cyclodepsipeptide. The A83586C- citropeptin hybrid will serve as a useful intracellular probe that will provide valuable insights into the mechanism of the antitumour action of this class, which may contribute to a greater understanding of cancer biology. The cyclodepsipeptide components of these molecules have been assembled via a 2+2+2 -fragment condensation strategy and a HATU-mediated macrolactamisation. In the case of the A83586C-citropeptin hybrid, a chemoselective coupling was performed between the fully elaborated N-hydroxybenzotriazole activated ester and the citropeptin cyclodepsipeptide.
date: 2007-04-30
id_number: PQ ETD:593515
oa_status: green
full_text_type: other
thesis_class: doctoral_open
language: eng
thesis_view: UCL_Thesis
primo: open
primo_central: open_green
verified: verified_manual
full_text_status: public
pages: 506
institution: UCL (University College London)
department: Department of Chemistry
thesis_type: Doctoral
citation:        Walters, M;      (2007)    Synthesis of A83586C/citropeptin hybrid and synthetic studies toward azinothricin.                   Doctoral thesis , UCL (University College London).     Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1446184/1/Walters.M.Thesis.pdf