Chemists at Otto von Guericke University Magdeburg have made progress in addressing antibiotic-resistant bacteria. Led by Professor Dieter Schinzer, the team produced key components of the natural compound Neosorangicin A in the lab for the first time. This achievement opens the way for targeted development of the substance as a reserve antibiotic candidate.
The researchers employed relay synthesis, creating critical segments first rather than the full complex molecule at once. These segments acted as intermediate stages toward the complete compound. The work demonstrates both the produced components and the overall process, with findings published in Chemistry—A European Journal.
Neosorangicin A is a secondary metabolite from myxobacteria that disrupts bacterial RNA polymerase, preventing genetic replication. It has shown activity against gram-negative bacteria, which are hard to treat due to their protective outer layer and pose rising challenges in hospitals globally.
The molecule features 16 chiral centers requiring exact spatial arrangements and is prone to rapid degradation. The new synthesis method allows precise chemical modifications to improve stability and effectiveness. The team used a convergent approach, preparing three complex building blocks separately before combining them through coupling reactions after up to 19 steps per subunit.
The World Health Organization views antibiotic resistance as a major global health threat. A 2024 Lancet study estimated 1.14 million direct deaths and 4.71 million associated deaths from resistant bacteria in 2021, with projections of up to 1.91 million direct deaths annually by 2050 without new solutions. Schinzer noted that natural compounds like this offer models for new structures, though further development is needed before clinical use.
