Chemists take a key step toward a new 'reserve' antibiotic against resistant bacteria

For the first time, chemists have built the critical molecular pieces of neosorangicin A, a natural substance long seen as a promising weapon against drug-resistant bacteria but far too complex to make in the laboratory. The team led by Professor Dieter Schinzer at Otto von Guericke University Magdeburg reported the advance in the journal Chemistry – A European Journal, and it clears one of the main obstacles to developing the compound as a future "reserve" antibiotic.

Rather than attempt the entire intricate molecule in one continuous sequence, the researchers used an approach called relay synthesis: they first assembled the most difficult sections separately, as intermediate stages, before joining them on the route to the full compound. That the individual building blocks now exist matters less than the fact that a viable path to making them has been demonstrated at all — a template other labs can follow.

Why it matters

Neosorangicin A is a secondary metabolite, a substance that soil-dwelling myxobacteria produce to fend off rival microbes. It works by jamming bacterial RNA polymerase, the enzyme microbes rely on to copy their genetic code and multiply. Crucially, earlier studies found it active against Gram-negative pathogens — bacteria wrapped in an extra outer membrane that shrugs off many existing drugs and that hospitals worldwide struggle to treat.

Reserve antibiotics are the drugs held back for infections that no longer respond to standard treatment, and the pipeline of new ones has been thin for decades even as resistance spreads. Naturally occurring molecules like neosorangicin A are attractive precisely because their structures are unfamiliar to bacteria, but that same complexity has kept them out of reach for chemists.

Turning laboratory building blocks into an approved medicine will still take years of further synthesis, testing and trials. What the Magdeburg work provides is a credible starting point — proof that one of nature's most stubborn antibiotic candidates can, in principle, be made by human hands.