Synthesis of Indole Alkaloids and Development of New Methodology

Forskningsoutput: AvhandlingDoktorsavhandling (sammanläggning)

Abstract

Natural products are compounds that exist naturally in living organisms, e.g.,
plants, animal and fungi. These compounds are likely biologically active and can
be used as pharmaceuticals for various diseases. Evolution has made it possible for
living organisms to produce these natural products as a defence mechanism against
various threats. In most cases, the organism only produces a small amount of the
natural product in question which makes it very difficult to get hold of a reasonable
amount to study, and even more so if we would like to use it as a medicine.
Furthermore, most natural products have a very complex three-dimensional
structure. The complexity of these molecules makes it very difficult to synthesise
them efficiently and have therefore enticed the synthetic organic community.
Besides the optimal goal of accessing the natural products, method development
can also lead to drug candidates with higher selectivity which ultimately means
that we can use less of a drug and experience much fewer side effects. Our research
interest is to develop strategies and methodologies and implement them on the
syntheses of natural products. In this thesis, we have explored several strategies
towards total syntheses of natural products as well as working with method
development.

The first part describes our efforts towards the total synthesis of perophoramidine
and its synthetic analogue, dehaloperophoramidine. Perophoramidine can be found
in a marine ascidian that is native to the south Pacific ocean. We wanted to utilise
the inherent structure and symmetry of the natural product in our planning to
maximize the likelihood of reactions leading to so-called "domino processes". We
then applied this strategy to the synthesis of perophoramidine and
dehaloperophoramidine, the latter with great success. We successfully made
dehaloperophoramidine in eight steps starting from isoindigo, a compound that can
be easily accessed.

The second part outlines our efforts towards the total synthesis of strictamine,
which is an alkaloid that can be isolated from the leaves of the Rhazya stricta plant.
The complexity of this natural product is ascribed to the highly congested
polycyclic structure. We intended to adopt a methodology that was previously
disclosed in our group to construct the complex ring system found in strictamine.
The synthesis is currently at an advanced state. The core structure of strictamine
was established and to complete the synthesis, two additional steps are required.
The third part of this thesis deals with the development of a new methodology to
access important scaffolds, indolines, that can be used in the synthesis of natural
products. The indoline scaffolds are reoccurring in natural products, and many of
of which have pharmaceutical properties. We were interested in synthesising
indoline scaffolds that have an all-carbon quaternary stereocenter.

Detaljer

Författare
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Naturvetenskap
  • Organisk kemi

Nyckelord

Bidragets titel på inmatningsspråkSyntes av Indol Alkaloider och Utveckling av Ny Metod
Originalspråkengelska
KvalifikationDoktor
Tilldelande institution
Handledare/Biträdande handledare
Tilldelningsdatum2019 apr 12
UtgivningsortLund
Förlag
  • Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering
Tryckta ISBN978-91-7422-645-4
Elektroniska ISBN978-91-7422-646-1
StatusPublished - 2019 mar
PublikationskategoriForskning

Nedladdningar

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Relaterad forskningsoutput

Anita Hoang, Popov, K. & Peter Somfai, 2017 feb 17, I : Journal of Organic Chemistry. 82, 4, s. 2171-2176 6 s.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Popov, K., Anita Hoang & Peter Somfai, 2015, I : Angewandte Chemie (International edition).

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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