Header

UZH-Logo

Maintenance Infos

Preparation of Indolenines via Nucleophilic Aromatic Substitution and Synthesis of Mangrolide Hybrids


Roesslein, Joel. Preparation of Indolenines via Nucleophilic Aromatic Substitution and Synthesis of Mangrolide Hybrids. 2021, University of Zurich, Faculty of Science.

Abstract

Within this PhD thesis two different areas of organic chemistry, heterocycles and antibiotics, will be discussed. In the first part a new method for the synthesis of indolenine, a benzo-fused N-heterocycle, will be introduced and in the second part the total synthesis of the antibiotic mangrolide hybrids will be presented.
Chapter 1: Heterocycles are important building blocks in natural products and drug development. Especially the N-benzo-fused heterocyclic indole and indolenine scaffolds are key in this area. A new method for the synthesis of indolenines has been developed giving a new access to this interesting type of heterocycles. Treatment of synthetic easily accessible nitriles with organolithium reagents lead upon heating to the indolenine formation. In the first part a broad substrate scope was prepared to show the flexibility and the wide acceptance of different functional groups by this new method. In the second part a mechanistic study was performed to give insight into the mechanism of this reaction and similar systems were tested. Finally, as an application new indolenine-based dyes have been synthesized.
Chapter 2: With the widespread resistance of bacteria to antibiotics new antibiotics are urgently needed. Therefore, isolation of antibiotic natural products and their synthesis is an important field in current research. The macrolide mangrolide A was isolated by the MacMillan group and was reported to have high activity against Gram-negative bacteria by a mode of action known from aminoglycosides. The optimized synthesis of the epoxide precursor of the D-mycaminose used in the first total synthesis approach of Dr. H. Hattori is reported and a short summary of Dr. H. Hattoris total synthesis of this structurally challenging natural product is provided. We hypothesized that mainly the carbohydrate part is responsible for the high activity of this antibiotic and therefore new mangrolide-hybrids have been synthesized for further studies of the activity of mangrolide A.

Abstract

Within this PhD thesis two different areas of organic chemistry, heterocycles and antibiotics, will be discussed. In the first part a new method for the synthesis of indolenine, a benzo-fused N-heterocycle, will be introduced and in the second part the total synthesis of the antibiotic mangrolide hybrids will be presented.
Chapter 1: Heterocycles are important building blocks in natural products and drug development. Especially the N-benzo-fused heterocyclic indole and indolenine scaffolds are key in this area. A new method for the synthesis of indolenines has been developed giving a new access to this interesting type of heterocycles. Treatment of synthetic easily accessible nitriles with organolithium reagents lead upon heating to the indolenine formation. In the first part a broad substrate scope was prepared to show the flexibility and the wide acceptance of different functional groups by this new method. In the second part a mechanistic study was performed to give insight into the mechanism of this reaction and similar systems were tested. Finally, as an application new indolenine-based dyes have been synthesized.
Chapter 2: With the widespread resistance of bacteria to antibiotics new antibiotics are urgently needed. Therefore, isolation of antibiotic natural products and their synthesis is an important field in current research. The macrolide mangrolide A was isolated by the MacMillan group and was reported to have high activity against Gram-negative bacteria by a mode of action known from aminoglycosides. The optimized synthesis of the epoxide precursor of the D-mycaminose used in the first total synthesis approach of Dr. H. Hattori is reported and a short summary of Dr. H. Hattoris total synthesis of this structurally challenging natural product is provided. We hypothesized that mainly the carbohydrate part is responsible for the high activity of this antibiotic and therefore new mangrolide-hybrids have been synthesized for further studies of the activity of mangrolide A.

Statistics

Downloads

0 downloads since deposited on 09 Feb 2022
0 downloads since 12 months

Additional indexing

Item Type:Dissertation (monographical)
Referees:Gademann Karl, Holland Jason Philip, Juricek Michal
Communities & Collections:07 Faculty of Science > Department of Chemistry
UZH Dissertations
Dewey Decimal Classification:540 Chemistry
Language:English
Place of Publication:Zurich
Date:2021
Deposited On:09 Feb 2022 08:00
Last Modified:19 Dec 2023 16:18
OA Status:Closed