Ph. D Research
My work was concerned with the determination of the absolute configuration of betalactam derivatives by means of circular dichroism techniques. Since the biological activity of these compounds is depended on the spatial orientation of the substituents around the betalactam ring, the simple method for the determination of an absolute configuration of such derivatives is necessary. In bicyclic systems, an absolute configuration at the bridgehead carbon atom seems to be especially important for biological properties.
Few years ago, Prof. Frelek and coworkers demonstrated that the positive sign of the amide CD band (at around 220 nm) corresponds to an R absolute configuration of the bridgehead carbon atom while the S configuration gives the negative sign.1,2 In my work I wanted to establish the scope and limitation of the newly introduced helicity rule. This particular attention was payed to the size of the additional ring in the bicyclic betalactam systems. I found that the rule can be applied to compounds with a five- and six-membered additional ring whereas the rule completely failed in the case of seven-membered rings. The CD spectra of the latest showed the opposite relations and were resembled to the spectra of monocyclic betalactams. This behaviour can be rationalized in terms of planarity of the amide chromophore. In azetidinons the chromophore is planar and the shapes of the CD curves are governed by nearby substituents in the vicinity of the chromophore. In bicyclic system with small or medium additional ring the chromophoric system is twisted which is a consequence of internal strain. In these cases an internal chirality of the chromophore becomes the primary factor responsible for the Cotton effect. In derivatives with seven-membered additional ring, however, the internal strain does not practically exist and the amide chromophoric system may return to its natural planar conformation. The experimental results and explanations of phenomena observed remain in a good agreement with computational analysis of the investigated structures. TD DFT calculations showed moderate conformational stability of the five- and six-membered 3,4 ring and high flexibility of seven-membered rings. Moreover, the calculated CD spectra showed satisfactory accordance to these which were measured.
1. Frelek, J.; £ysek, R.; Borsuk, K.; Jagodzinski, J.; Furman, B.; Klimek, A.; Chmielewski, M., Enantiomer 2002, 7, 107-114.
2. £ysek, R.; Borsuk, K.; Chmielewski, M.; Ka³uba, Z.; Urbanczyk-Lipkowska, Z.; Klimek, A.; Frelek, J., J. Org. Chem. 2002, 67, (5), 1472-1479.
3. Frelek, J.; Kowalska, P.; Masnyk, M.; Kazimierski, A.; Korda, A.; Woznica, M.; Chmielewski, M.; Furche, F.; Chemistry – A European Journal 2007, 13, (23), 6732-6744
4. Chmielewski, M.; Cierpucha, M.; Kowalska, P.; Kwit, M.; Frelek, J.; Chirality 2008, 20, 621-627