Conglomerates surface in new resolution strategies

PhD ceremony: Mr. M.W. van der Meijden, 12.45 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Conglomerates surface in new resolution strategies

Promotor(s): prof. A.J. Minnaard, prof. R.M. Kellogg

Faculty: Mathematics and Natural Sciences

This research covers 4 subjects. First a recently discovered process for the conversion of a conglomerate, a 50:50 mechanical mixture of enantiomers, into a single enantiomer by means of grinding of the solid while racemization occurs in solution. This technique was used in the successful synthesis of the bestselling drug, Clopidogrel (Plavix) used for treatment of high blood pressure.

Next we attempted to connect resolution agents to a surface (sort of chip) to be able to do a complete screening with many resolving agents in one experiment and in this way shorten the required time for finding the right resolution method and conditions. By using a stamp with a pattern it was possible to apply a controlled pattern of the desired compound. Several practical problems have so far hindered practical application, although highly useful insights in the field of crystallization in both 2D as 3D have been obtained.

Some members of an unusual family of chiral molecules, the helicenes characterized by their staircase-like structures, have also been investigated. An amine-compound from the family of helicenes has been synthesized via a short and scalable synthesis. It was possible to separate the enantiomers and this made it possible to study the chiral and optical properties also on gold and copper surfaces.

Finally, the synthesis of a helicene with an acid functionality has been accomplished. Many routes had to be examined before a success approach was developed. Preliminary work on the absorption of this helicene on metal surfaces has been carried out.