Penicillin-based antibiotics contain a five-membered hydrocarbon ring that has a sulphur and a nitrogen atom. A team of researchers from Bielefeld University and the RUB has now succeeded in selectively producing this important substructure. The targeted design of such structures enables the establishment of substance libraries that the pharmaceutical industry can use to find new active substances. The researchers report their work in the journal “Nature Communications” of 16 May 2018.
In principle, the ring structures can be generated from easily accessible precursors, the so-called 3-thiazolines. The ring is already prefabricated and only a double bond still has to be converted into a single bond by reduction, i.e. addition of hydrogen. Although 3-thiazolines have been known for decades, this conversion proved difficult.
Enzymes as biocatalysts
Nadine Zumbrägel, doctoral student at Prof Dr Harald Gröger’s Chair of Organic Chemistry I at Bielefeld University, has now succeeded for the first time in reducing 3-thiazolines to the desired target compounds in a highly selective manner without any side reactions. To this end, she used so-called imine reductases as biocatalysts.
Calculations make results comprehensible
The researchers also succeeded in extending the reduction method to other sulphur-containing ring structures, thereby developing a platform technology. They were also able to show that this reduction method can be applied on an enlarged laboratory scale. Quantum mechanical calculations by Prof Dr Stefan Huber, Professor at the Chair of Organic Chemistry I at the RUB, made the experimental observations comprehensible. Dr Christian Merten, head of a junior research group at the Chair of Organic Chemistry 2, was able to clarify the spatial structure of the target molecules using spectroscopy.
Original publication:
Nadine Zumbrägel, Christian Merten, Stefan M. Huber, Harald Gröger: Enantioselective reduction of sulfur-containing cyclic imines through biocatalysis, in: Nature Communications, 2018, 9, 1949 DOI: 10.1038/s41467-018-03841-5