Total synthesis of naturally occurring glycosylated tetramic acids

The first synthesis of a naturally occurring 3-acyl tetramic acid glycoconjugate was investigated. An endofungal metabolite called epicoccamide D was synthesized for the first time. This was accomplished in 19 steps resulting in a 17% overall yield. The total synthesis was built on a modular base to possibly adapt the concept to other natural products. The key steps of the synthesis were: a β-selective glycosylation followed by a C-2 epimerisation reaction of the sugar moiety, a HWE olefination, an aminolysis reaction to install the L-alanine residue, followed by a Lacey-Dieckman cyclisation. The 7S stereocenter was established using a rhodium based homogeneous catalyst and applying a high-pressure hydrogenation to the tetramic acid. Stable BF2-chelate complexes are here utilized to disarm its metal chelating properties. This procedure allowed assignment of the hitherto unknown absolute configuration of the natural product by comparison of NMR data and optical rotation. Additional side chains of other naturally occurring 3-acyl tetramic acids were synthesized by applying similar retrosynthetic approaches used for epicoccamide D total synthesis. The dissacharide terminated alkyl chain of ancorinoside B bearing a galactose and a glucuronic acid was successfully synthesized including two consecutive β-selective glycosylations and a C-6 oxidation protection procedure. Also a more substituted side chain for the total synthesis of virgeneone was synthesized ready to couple it to a β-mannose as elaborated for epicoccamide D total synthesis. Assembly of this side chain included an ozonolysis reaction and involved a Grignard reaction. With both side chains in hand, the total synthesis of the two compounds ancorinoside B and virgineone can be performed by applying the protocol derived for epicoccamide D total synthesis. All additional and new steps of these two side chains have been carried out within this thesis. Additionally, chemical N-glycosylation was investigated to allow access to aurantosides by employing a Fukayama-Mitsunobu reaction. The behaviour of the tetramic acids, 3-acyl tetramic acids and their boron complexes towards Lewis-acidic glycosylation conditions was examined as well. The last section of this thesis deals with the stereoinduction of the successfully applied BF2 complexes in terms of their behavior heterogeneous hydrogenations. This process is briefly investigated by building a diethyl boron complex of a tetramic acid.

Level thesis:degree_level

thesis.doctoral

Grantor dc:publisher

Universität Bayreuth

Year

2015

Author dc:creator

• Loscher, Sebastian

Contributors dc:contributor

• Schobert, Rainer

Repository record source_url

https://epub.uni-bayreuth.de/id/eprint/2148/

OAI identifier oai:identifier

oai:epub.uni-bayreuth.de:2148