Synthesis of an oligopeptide library

authored by

Tim Seedorf

supervised by

Andreas Kirschning

Abstract

The oligopeptides cystobactamid and Myxovalargin A are natural products produced by myxobacteria. Both secondary metabolites exhibit high antibacterial activity and are currently in different stages of preclinical antibiotic development. In the present work syntheses of these natural products and their analogs were performed to establish their total synthesis and to optimize their antibacterial profile, respectively. Cystobactamids represent a new class of antibiotics. Since their discovery structure-activity-relationships (SAR) were stated through natural product isolation and totalsynthesis. In this work the SAR studies were extended by synthesis of an agent library und the antibacterial profile was optimized against representatives of all ESKAPE pathogens utilizing structural simplification, bioisosterism and novel structural motifs. Myxovalargin A exhibits biological activity against tuberculosis. Insufficient access through fermentation prevented the elucidation of the absolute stereoconfiguration for a long time. Therefore, synthetic studies towards the total synthesis of Myxovalargin A were performed in this work with the long term aim to pave the way for a medicinal chemistry program. A combination solid and liquid phase synthesis enabled the provision of advanced fragments of the natural product.

Organisation(s)

Institute of Organic Chemistry

Type

Doctoral thesis

No. of pages

430

Publication date

2023

Publication status

Published

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.15488/14437 (Access: Open)