Terpenes and their derivatives exert important biological and pharmaceutical functions. Starting out from a few basic building blocks nature elegantly builds up complex structures. Particularly challenging chemically are bridged ring systems such as eucalyptol.
Chemists at the Technische Universität München (TUM), in Germany, have now developed a catalyst that initiates the formation of such compounds. A special feature of the catalyst is that it self-assembles from smaller units.
Their research is published in the journal Nature Chemistry.
Eucalyptol, or 1.8-cineole, is used in many cough medicines. Chemically it consists of a ring of six carbon atoms which are additionally bridged. Starting out from geraniol, the main constitutent of the scent of geranium, this double ring is formed by a so-called tail-head-cyclisation.
The biggest challenge of producing something artificially, the scientists say, is that as a first step a high-energy intermediate state is formed, in which the molecule has a positive charge. Without a catalyst, the molecule could further react in different directions and the desired product would be one of many and the yield low.
'Our catalyst stabilises the transition state and directs the reaction in the right direction,' said Konrad Tiefenbacher, Professor of Organic Chemistry at the Technische Universität München. 'In solution these reactions were previously not feasible.'
The catalyst of the reaction is also special: four resorcinol molecules are linked to form a large ring consisting of 16 carbon atoms. Six of these molecules self-assemble in solution to a large, octahedron-like cage. In its interior the cyclisation reaction takes place.
The electron-rich aromatic ring systems of the resorcinol-blocks appear to stabilise the positive charge of the intermediate state. Similar to the reaction pocket of the cyclase enzyme of the eucalyptus tree, the catalyst thus prevents undesirable side reactions.
According to the scientists, if parent compounds other than geraniol were used a variety of other products could be feasible.
'Eucalyptol is only a first step,' said Tiefenbacher. 'Our ultimate goal is the production of compounds with much higher complexity, such as taxol, which is used in the fight against cancer.'
