When developing new drugs, one thing is particularly important: finding and producing the right molecules that can be used as active ingredients. The key elements of some drugs, such as penicillin, are small, tri- or quadripartite ring molecules. A team led by Prof Frank Glorius from the Institute of Organic Chemistry of the University of Münster (Germany) has now developed a method for efficiently converting readily available basic materials into such small, high-grade ring molecules. The product has a structure reminiscent of a line drawing of a house, hence its name “housane”. The reaction is triggered by a photocatalyst that transfers light energy to the molecules to enable the conversion.
Small ring molecules are under strong tension similar to a bent branch. The release of tension can drive downstream reactions, thereby enabling efficient access to valuable products. However, high-tensile molecules are difficult to produce. Previous methods for producing housane often require “harsh” conditions, such as high temperatures, and they do not work with many additional atoms or atom groups, known as functional groups, on the starting molecules. However, it is precisely these functional groups that are crucial for the properties of a molecule.
The team used certain hydrocarbons (1,4-dienes) as the starting material. These normally undergo undesirable side reactions when exposed to light. However, the researchers succeeded in suppressing these deviating reaction pathways by adapting the side chains of the molecules in the starting material. This made the process more orderly and predictable. In addition, when these side reactions are suppressed, the starting materials can “close” themselves into a ring structure to build up tension. “This process is normally difficult to achieve because it is energetically ‘uphill’ and requires additional momentum. Photocatalysis provides the necessary energy,” Frank Glorius explains. Computer-aided analyses helped the team understand how the reaction works.
The new method makes it possible to produce housane easily and efficiently, and it expands the possibilities for how the high-tensile skeleton can be used to build complex molecules. The researchers expect their work to benefit both basic research and practical applications, including drug manufacturing and materials development.
Nature Synthesis
Experimental study
Not applicable
Divergent housane synthesis via intramolecular [2 + 2] cycloaddition of 1,4-dienes
19-Feb-2026