Synthesis of Indole Alkaloids and Development of New Methodology

Research output: ThesisDoctoral Thesis (compilation)

Abstract

This thesis describes our efforts towards the total synthesis of natural products and the development of a new
methodology to afford a synthetically important scaffold.

Chapter 2 outlines our efforts towards the total synthesis of a marine natural product, perophoramidine as well
as our completed synthesis of dehaloperophoramidine. The focus of the studies was to develop an efficient and
concise strategy to afford the natural products. We aimed at utilising the inherent structure and symmetry of the
natural product to encourage domino processes and gain access to the key features. The vicinal quaternary
stereocenters were installed by employing Overman’s diastereoselective dialkylation protocol. Two new domino
processes were discovered. The first domino process led to the formation of the ortho-amide and careful
investigation of its reactivity led to the discovery of the second domino process which ultimately delivered
dehaloperophoramidine. The synthesis was completed in eight steps starting from isoindigo.

Chapter 3 describes our efforts towards the total synthesis of strictamine. The key features of strictamine that
need to be addressed when pursuing the synthesis are: (i) the quaternary stereocenter, (ii) the central
cyclohexane moiety (D ring) with four stereocenters, and (iii) the cage-like methanoquinolizidine core. We aimed
at accessing these key features through intramolecular Heck reaction to access the central D ring with parts of
the substitution pattern already present and the quaternary stereocenter. For the methanoquinolizidine core, we
planned to adopt our previously described domino carbopalladation/carbonylation protocol. The synthesis is in
an advanced state with two additional functionalisation left in order to access the target compound. Described in
this chapter is our effort to access the core structure of strictamine with all the rings installed.

The third part of this thesis deals with the development of a new methodology to access indoline scaffolds that
feature an all-carbon quaternary stereocenter. We were able to synthesise allyl anilines through the regio- and
stereoselective ring-opening of vinyl aziridines with 2-iodoaniline. The final indoline scaffold was furnished by
intramolecular Heck reaction with concomitant formation of the quaternary stereocenter.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Natural Sciences
  • Organic Chemistry

Keywords

  • total synthesis, indole alkaloids, Domino reactions, vicinal quaternary stereocenters, quaternary stereocenter, indoline synthesis, communesin alkaloid, perophoramidine, dehaloperophoramidine, akuammiline alkaloids, strictamine, intramolecular Heck reaction, domino carbopalladation carbonylation, indoline alkaloids
Translated title of the contributionSyntes av Indol Alkaloider och Utveckling av Ny Metod
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2019 Apr 12
Place of PublicationLund
Publisher
  • Lund University, Faculty of Science, Center for Chemistry and Chemical Engineering
Print ISBNs978-91-7422-645-4
Electronic ISBNs978-91-7422-646-1
Publication statusPublished - 2019 Mar
Publication categoryResearch

Bibliographic note

Defence details Date: 2019-04-12 Time: 09:00 Place: Sal B, Kemicentrum, Naturvetarvägen 14, Lund External reviewer(s) Name: Poulsen, Thomas Title: Ass. Professor Affiliation: Aarhus University, Denmark ---

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