Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance
Variolin B, a marine natural product isolated from the Antarctic sponge Kirkpatrickia variolosa, possesses a rare heterocyclic framework and is a potent CDK inhibitor. Such properties have prompted the industry partner associated with this project, namely the German chemical commodities company BASF...
Main Author: | |
---|---|
Format: | Doctoral or Postdoctoral Thesis |
Language: | English |
Published: |
2018
|
Subjects: | |
Online Access: | http://hdl.handle.net/1885/151313 https://doi.org/10.25911/5d514ee4c4d8f https://openresearch-repository.anu.edu.au/bitstream/1885/151313/5/b2879994x_Sharp_Phillip%20Patrick.pdf.jpg |
id |
ftanucanberra:oai:openresearch-repository.anu.edu.au:1885/151313 |
---|---|
record_format |
openpolar |
spelling |
ftanucanberra:oai:openresearch-repository.anu.edu.au:1885/151313 2024-01-14T10:01:56+01:00 Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance Sharp, Phillip Patrick 2018-11-21T08:49:02Z 1 v. (various pagings). http://hdl.handle.net/1885/151313 https://doi.org/10.25911/5d514ee4c4d8f https://openresearch-repository.anu.edu.au/bitstream/1885/151313/5/b2879994x_Sharp_Phillip%20Patrick.pdf.jpg en_AU eng b2879994 http://hdl.handle.net/1885/151313 doi:10.25911/5d514ee4c4d8f https://openresearch-repository.anu.edu.au/bitstream/1885/151313/5/b2879994x_Sharp_Phillip%20Patrick.pdf.jpg Author retains copyright QD421.S53 2011 Alkaloids Synthesis Organic compounds Synthesis Sponges Antarctic Ocean Marine natural products Thesis (PhD) 2018 ftanucanberra https://doi.org/10.25911/5d514ee4c4d8f 2023-12-15T09:33:10Z Variolin B, a marine natural product isolated from the Antarctic sponge Kirkpatrickia variolosa, possesses a rare heterocyclic framework and is a potent CDK inhibitor. Such properties have prompted the industry partner associated with this project, namely the German chemical commodities company BASF, to select this compound as a lead for the development of new agrochemicals. This thesis details the development of new synthetic methods specifically designed to produce complex heterocyclic frameworks related to variolin B. The synthetic plan, which involved consecutive electrophile-promoted nucleophilic ring-closure reactions of 1-[2-(buta-1,3-diynyl)pyridyl]ureas potentially leading to pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidin-9(8H)-ones, is outlined in Chapter One. The first part of Chapter Two describes the synthesis of alkynylphenylureas as model cascade cyclisation precursors and the second part details the outcomes of reactions of these model compounds with various sources of iodine. The reactions delivered mono-cyclised compounds in some cases although intermolecular side-reactions prevented cascading cyclisation reactions from occurring. Details of the successful development of consecutive gold-catalysed nucleophilic ring-closure reaction of 2-(buta-1,3-diynyl)phenylureas that deliver pyrimido[1,6-a]indol-1(2H)-ones are provided in Chapter Three. The effect that substituents have on the outcome of these gold-promoted reactions were also assessed and it was found that N,N'-disubstituted cyclisation precursors give 1-methylene-1H-imidazo[1,5-a]indol-3(2H)-ones as the major products. Chapter Four outlines the preparation of pyridine-based cyclisation precursors and attempts to synthesise variolin B by applying the gold-catalysed cyclisation methodology to them. These reactions led to mono-cyclised products in some cases but side reactions were also observed. Many of the heterocycles produced during the course of this work are unprecedented and, accordingly, they are being tested for their agrochemical ... Doctoral or Postdoctoral Thesis Antarc* Antarctic Antarctic Ocean Australian National University: ANU Digital Collections Antarctic The Antarctic Antarctic Ocean |
institution |
Open Polar |
collection |
Australian National University: ANU Digital Collections |
op_collection_id |
ftanucanberra |
language |
English |
topic |
QD421.S53 2011 Alkaloids Synthesis Organic compounds Synthesis Sponges Antarctic Ocean Marine natural products |
spellingShingle |
QD421.S53 2011 Alkaloids Synthesis Organic compounds Synthesis Sponges Antarctic Ocean Marine natural products Sharp, Phillip Patrick Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
topic_facet |
QD421.S53 2011 Alkaloids Synthesis Organic compounds Synthesis Sponges Antarctic Ocean Marine natural products |
description |
Variolin B, a marine natural product isolated from the Antarctic sponge Kirkpatrickia variolosa, possesses a rare heterocyclic framework and is a potent CDK inhibitor. Such properties have prompted the industry partner associated with this project, namely the German chemical commodities company BASF, to select this compound as a lead for the development of new agrochemicals. This thesis details the development of new synthetic methods specifically designed to produce complex heterocyclic frameworks related to variolin B. The synthetic plan, which involved consecutive electrophile-promoted nucleophilic ring-closure reactions of 1-[2-(buta-1,3-diynyl)pyridyl]ureas potentially leading to pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidin-9(8H)-ones, is outlined in Chapter One. The first part of Chapter Two describes the synthesis of alkynylphenylureas as model cascade cyclisation precursors and the second part details the outcomes of reactions of these model compounds with various sources of iodine. The reactions delivered mono-cyclised compounds in some cases although intermolecular side-reactions prevented cascading cyclisation reactions from occurring. Details of the successful development of consecutive gold-catalysed nucleophilic ring-closure reaction of 2-(buta-1,3-diynyl)phenylureas that deliver pyrimido[1,6-a]indol-1(2H)-ones are provided in Chapter Three. The effect that substituents have on the outcome of these gold-promoted reactions were also assessed and it was found that N,N'-disubstituted cyclisation precursors give 1-methylene-1H-imidazo[1,5-a]indol-3(2H)-ones as the major products. Chapter Four outlines the preparation of pyridine-based cyclisation precursors and attempts to synthesise variolin B by applying the gold-catalysed cyclisation methodology to them. These reactions led to mono-cyclised products in some cases but side reactions were also observed. Many of the heterocycles produced during the course of this work are unprecedented and, accordingly, they are being tested for their agrochemical ... |
format |
Doctoral or Postdoctoral Thesis |
author |
Sharp, Phillip Patrick |
author_facet |
Sharp, Phillip Patrick |
author_sort |
Sharp, Phillip Patrick |
title |
Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
title_short |
Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
title_full |
Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
title_fullStr |
Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
title_full_unstemmed |
Consecutive gold[I]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
title_sort |
consecutive gold[i]-catalysed cyclisation reactions leading to polyfused heterocycles of agrochemical relevance |
publishDate |
2018 |
url |
http://hdl.handle.net/1885/151313 https://doi.org/10.25911/5d514ee4c4d8f https://openresearch-repository.anu.edu.au/bitstream/1885/151313/5/b2879994x_Sharp_Phillip%20Patrick.pdf.jpg |
geographic |
Antarctic The Antarctic Antarctic Ocean |
geographic_facet |
Antarctic The Antarctic Antarctic Ocean |
genre |
Antarc* Antarctic Antarctic Ocean |
genre_facet |
Antarc* Antarctic Antarctic Ocean |
op_relation |
b2879994 http://hdl.handle.net/1885/151313 doi:10.25911/5d514ee4c4d8f https://openresearch-repository.anu.edu.au/bitstream/1885/151313/5/b2879994x_Sharp_Phillip%20Patrick.pdf.jpg |
op_rights |
Author retains copyright |
op_doi |
https://doi.org/10.25911/5d514ee4c4d8f |
_version_ |
1788056735805603840 |