Syntheses of natural bioactive 3-acyltetramic acids and derivatives

This thesis was divided into four major parts. The first three parts were dedicated to the syntheses of macrocidin A and related analogues, to the synthesis of torrubiellone D and to the syntheses of quinolactacin A2 and B2. The last part involved the synthesis of potential adenylyl cyclase inhibitors and their biochemical evaluation. The main tasks of this thesis revolved around the natural product macrocidin A and its analogues (incorporating different ring sizes or additional donor atoms in the side chain). Therefore, a L tyrosine derived tetramic acid was coupled to different side chains, which were synthesised separately, by applying varying 3 acylation conditions. Macroetherification via palladium catalysis and subsequent deprotection provided the desired macrocycles. The second target natural product of this thesis was torrubiellone D. The synthesis consisted of two major parts: the preparation of the tetramic acid core and of the unsaturated aldehyde fragment, needed to install the 3-acyl side chain. The coupling of both fragments by ketenylidene(triphenyl)phosphorane mediated 3-acylation has been tested, but the desired product could not be purified and isolated to date. The last natural products covered in this thesis were quinolactacins A2 and B2. Quinolactacin A2 was synthesised in a new and efficient way employing two different routes. The same sequences were carried out to generate quinolactacin B2, but the route could not be completed to date. In the last part of the thesis, potential tetramic acid based inhibitors for the adenylyl cyclase were synthesised.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Universität Bayreuth

Year

2015

Author dc:creator

• Kroscky, Anders

Contributors dc:contributor

• Schobert, Rainer

Repository record source_url

https://epub.uni-bayreuth.de/id/eprint/2077/

OAI identifier oai:identifier

oai:epub.uni-bayreuth.de:2077