MOZARTKUGELN · Novel, switchable chiral stationary phases

Final Activity Report Summary - MOZARTKUGELN (Novel, switchable chiral stationary phases)

Studies carried out within the Marie Curie Project focused on the application of click chemistry, i.e. of an efficient synthetic method, for the development of new cinchona-alkaloids (eq. quinine) based on chiral stationary phases (CSPs). They were an important tool for the separation of racemates; that is mixtures of steroisomers, both in industry and academia. Making the CSP required broad knowledge covering organic, supramolecular and physical chemistry. It practically meant that one should covalently immobilise an appropriate selector, responsible for chiral recognition, onto appropriate solid support using non-invasive linker and compatible chemistry. In the frame of this project we developed such an efficient and mild protocol for immobilisation of cinchona alkaloids based on ligands onto silica gel or polymer resin. This method utilised all advantages of click chemistry, such as terminal alkyne and azide reaction, and was highly competitive to existing protocols. Moreover our method was general, meaning that it could be used for any kind of the terminal alkyne-azide pair. Using this technology, several novel CSPs were prepared and tested in the separation of the large number of racemates. For these studies we investigated and compared our CSPs with the existing CSPs in cases where the selectors were immobilised by the common method. These studies showed that click-linker was not destructive for global chiral recognition (or else separation) process and exhibited negligible level of unwanted non-specific interaction. Moreover, it offered an enhanced efficiency for selected racemates when compared with the commercial CSPs. Others CSPs developed during MCF allowed for chiral separation of important classes of compound including mandelic acid and derivatives, anti-inflammatory drugs (profens) and agrochemicals (dichloroprop and related herbicides). Click-immobilisation and favourable characteristics of click-linker were being further explored in the fellow and host laboratories. Another work within MCF project covered the synthetic chemistry of cinchona alkaloids. They possessed a status of privileged catalysts and resolving materials, which were also used in industry, there was therefore increasing demand for a development of new, more efficient ways of their easy modification and structure diversification. Within the project we developed a practical method for the conversion of cinchona alkaloids into their didehydro derivatives, which were click chemistry substrates, without the use of expensive and time-consuming chromatographic purification. Using click-chemistry we also synthesised a library of new cinchona derivatives of zwitterionic and dendrimer-like structures which were in the process of screening (organocatalysts and selectors) by the time of the project completion.

Data: CORDIS, © European Union