Towards the Syntheses of Biologically Relevant Secondary Metabolites
Date
2016
Authors
Harris, Eric Benjamin Jacques
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
The realm of natural product synthesis constitutes a major part
of the interactions between chemistry and the living world. By
designing and developing new synthetic routes to natural
products, a better insight is gained in terms of new methodology,
biological activity and structural novelty. As the field of
natural products chemistry advances, ideal syntheses must be
strived towards with the investigation of new methodology with
high efficiency. Outlined herein are efforts towards the
synthesis of four natural products of varying synthetic
interests. Although many factors drive interest in their
synthesis, they are united by a common goal of pursuing good
synthesis.
(+-)-Angelmarin (43) has potential a therapeutic agent in the
treatment of pancreatic cancer and was synthesised in only 7
linear steps without the use of protecting groups. This was
enabled by the recently developed gold(I) catalysed
intramolecular hydroarylation chemistry which allowed synthesis
of the key coumarin heterocycle in (+-)-columbianetin (44) under
mild conditions from the propiolate ester.
Investigations were made into the synthesis of the ochrosamines A
(117) and B (118), isolated from the endangered rainforest tree
Ochrosia moorei, exploring the scope and limitations of novel
chemistry such as the vinyl aziridine rearrangement and
interrupted Fischer indole synthesis. A number of interesting
results were obtained from which much was learnt about the
polycyclic system.
The hasubanan framework (204) was of synthetic interest as the
unnatural enantiomer has potential as a new opiate analogue. The
research hoped to expand on recently developed methodology for an
intramolecular Alder-ene reaction and its application in a high
value context.
Lastly, significant progress was made towards the synthesis of
bicuculline (228) with the successful synthesis of the advanced
intermediate (326) utilising an innovative osmium catalysed
intramolecular amidohydroxylation reaction. This carries the
possibility of developing an enantioselective synthesis. It is
hoped that the natural product can ultimately be synthesised from
this late stage material.
Description
Keywords
Bicuculline, amidohydroxylation, hasubanan, ochrosamine, columbianetin, angelmarin, chemistry, natural products
Citation
Collections
Source
Type
Thesis (PhD)
Book Title
Entity type
Access Statement
License Rights
Restricted until
Downloads
File
Description