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RESEARCH PROGRAMS

From the very start Syncom has been active in fundamental research on various chiral technologies.

Discovery of Dutch Resolution at Syncom (a fast method to separate enantiomers) led to the establishment of a consortium with DSM Research (Dr. Bernard Kaptein) and the University of Nijmegen (Prof. Elias Vlieg) to determine how and why this method works. The technology office of the Dutch National Science Foundation provided support for a broad ranging investigation that revealed that solid solution formation and nucleation inhibition were critical components of the method for the separation of enantiomers. This has led to generalized protocols for resolutions wherein e.g. designed nucleation inhibitors are used together with a single resolving agent. All of the Syncom research has been and still is directed by Prof. Richard M. Kellogg with whom both Ton Vries and Robert Hof obtained their PhD degrees.

 

UCT

The work of the consortium was continued with European Funds in the Ultimate Chiral Technology (UCT) project. In addition to further development of Dutch Resolution, attention turned to the behaviour of conglomerates. Prof. Donna Blackmond, now at Scripps Research Institute, participated in the consortium for some time. Armed with previously obtained knowledge we were able in a multidisciplinary effort to develop a completely new method for the deracemization of certain conglomerates to obtain pure enantiomers. For a conglomerate readily racemizable in solution the extraordinarily simple process of hard grinding is sufficient to convert it in essentially quantitative yield and absolute enantiomeric excess into a single enantiomer. This remarkable process is powered by Ostwald ripening, a phenomenon well known in crystal technology but never before applied in chiral technology. The UCT project also led to methods for preferential crystallization of (non-racemizable) conglomerates, transition metal catalyzed deracemizations of amines and to new uses of enzymes in chiral syntheses.

 

IBOS

The enzymic work has been developed further by participation in the programme Integrated Biochemical and Organic Synthesis (IBOS) supported by the Dutch National Science Foundation and the Ministry of Economic Affairs. Applications of oxidative enzymes for selective hydroxylation of organic substrates and the use of enzymes for construction of industrially relevant heterocyclic compounds are major areas of investigation.

 

RESOLVE

Syncom currently also participates in a project RESOLVE, supported with European funds, in which surface science and theoretical groups at Barcelona, Liverpool, Eindhoven, Mons and Leuven cooperate with Syncom in the use of Dutch Resolution to direct chiral assemblies on surfaces and also in solution. We expect the first articles on the functionalisation of surfaces shortly. In the course of this work a new synthesis of the industrially important drug Clopidogrel (Plavix) was developed using the grinding technology. Further examples of the application of this technology have been developed.

 

TI Pharma

Syncom has joined the public-private partnership Top Institute Pharma (TI Pharma) by participating in a consortium formed with Synvolux Therapeutics and University Medical Center Groningen and focuses on designing a versatile drug delivery system for inflammatory diseases and cancer (read more >).

 

In the course of these research programs four PhD students have obtained their degrees, various trainees have participated and several visiting scientists have been involved in this chiral technology program. Many publications have appeared based on this research, plenary lectures have been given at various conferences and review articles have been published.

The technology developed for the preparation of pure enantiomers either by resolution, deracemisation of asymmetric catalysis and asymmetric synthesis has been incorported into the technology package offered by Chirality First Time Right.