RESEARCH INTERESTS

Synthesis of enantiomerically pure, conformationally restricted derivatives of homophenylalanine and of its heteroanalogs by crystallization-induced asymmetric transformation (CIAT) coupled with the aza-Michael addition (A) and electrophilic lactonization (C). Study of simultaneous CIAT taking place at two stereogenic centers (B). Utilization of such asymmetric transformation in the synthesis of natural polysubstituted amino acids and their derivatives. Stereoselective  transformations of the prepared g-oxosubstituted a-aminocarboxylic acids.

 

 

CIAT is promising technique for the control of stereochemistry on the chiraly labile stereogenic centers. The principal requirement for this type of asymmetric transformation is that one of the isomers must be crystalline at a convenient temperature and mustn't form a solid solutions or quasi-racemates.

Because racemization and crystallization take place simultaneously, the relative rates between crystal growth and racemization are likely to be important. However, for the industrial applications mainly it is more convenient when the racemization (epimerization) takes faster than the crystallization. When both these conditions are fulfilled the desired enantiomer (diastereoisomer) can be isolated from the starting mixture by simple filtration and the yields reach theoretical    100 % regardless the equilibrium in the solution.[31]

Our research interests are devoted to the systematic study of CIAT applications for last several years. We have discovered and optimized several CIAT processes in tandem with aza-Michael addition of chiral N-nucleophiles[21,25] or with the addition of achiral amines to the chiral unsaturated substrates precursors[26], and also the CIAT mechanism of the stereoconvergent lactonization of g-hydroxy-g-aryl-a-aminocarboxylic acids.[30] We have achieved optimization of CIAT procedure with simultaneous formation of two new stereogenic centers.[29] We also developed the synthetically useful pathway leading to the substituted homophenylalanine derivatives via easy accessible diastereoisomeric salt formation.[23]

 

 

Bibliography:

31. Jakubec, P.; Kolarovic, A.; Berkes, D.: Crystallization-induced asymmetric transformations in the synthesis of active prarmaceutical substances., Materials Structure, 2005, 12, 189-191.

30. Berkes, D.; Kolarovic, A.; Manduch, R.; Baran, P.; Povazanec, F.: Crystallization-Induced Asymmetric Transformations (CIAT): Stereoconvergent Acid-Catalyzed Lactonization of Substituted 2-Amino-4-Aryl-4-Hydroxybutanoic Acids., Tetrahedron-Asymmetry, 2005, 16, 1927-1934.

29. Kolarovic, A.; Berkes, D. A.; Baran, P.; Povazanec, F.: Crystallization-Induced Asymmetric Transformation (CIAT) With Simultaneous Epimerization at Two Stereocenters. A Short Synthesis of Conformationally Constrained Homophenylalanines.. Tetrahedron Lett., 2005, 46, 975-978.

28. Berkes D.;Gattnar O.;Manduch M.;Varga I.;Kmetty G.;Snuparek V.;Marko M.;Michalak K.;Siska K.:Sposob pripravy hydrogenhalogenidov etylesteru kyseliny 1-metyl-4-fenyl-4-piperidin-4-karboxylovej a medziprodukty na jeho vykonavanie. SK-Pat. 2005, SK-284 526.

27. Berkes, D.; Kolarovic, A.; Raptis, R. G.; Baran, P.: Absolute Structure Determination of (2R,1 ' S)-2-(1 '-Benzyl-2 '-Hydroxyethylamino)-4-Phenylbutanoic Acid.. J. Mol. Struct., 2004, 697, 101-107.

26. Jakubec, P.; Berkes, D. A.; Povazanec, F.: Crystallization-Induced Asymmetric Transformation. Application to Conjugate Addition of Benzylamine to Amides of Benzoylacrylic Acid.. Tetrahedron Lett., 2004, 45, 4755-4758.

25. Safar P., Horvathova H., Korenova A., Berkes D.: 4-Heteroaryl-4-oxobutenoic acids in the synthesis of nonproteinogenic a-amino acids.. Annals of the Polish Chemical Society, 2004, 3, 76-80.

24. Safar P., Korenova A., Berkes D., Horvathova H.: Enantiomerically pure homotryptophane derivatives.. Chem. Listy, 2004, 98, 660-661.

23. Berkes, D.; Lopuch, J.; Proksa, B.; Povazanec, F.: Optical Resolution of Ethyl 2-(Benzylamino)-4-Oxo-4-Phenylbutanoate With Tartaric Acid - A Practical Synthesis of D-Homophenylalanine.. Chem. Pap., 2003, 57, 350-354.

22. Safar P., Berkes D., Pronayova N.: 4-(1-Benzensulfonyl-1H-pyrrol-3-yl, resp. 1H-indol-3-yl)-4-oxobut-2-enova kyselina v synteze aminokyselin.. Chem. Listy, 2003, 97, 761-762.

21. Kolarovic, A.; Berkes, D.; Baran, P.; Povazanec, F.: Crystallization-Induced Dynamic Resolution (CIDR) and Its Application to the Synthesis of Unnatural N-Substituted Amino Acids Derived From Aroylacrylic Acids.. Tetrahedron Lett., 2001, 42, 2579-2582.

20. Berkes, D.; Kolarovic, A.; Povazanec, F.: Stereoselective Sodium Borohydride Reduction, Catalyzed by Manganese(II) Chloride, of Gamma-Oxo-Alpha-Amino Acids. A Practical Approach to Syn-Gamma-Hydroxy-Alpha-Amino Acids.. Tetrahedron Letters, 2000, 41, 5257-5260.

19. Uher, M.; Berkes, D.: 2,5-Disubstituted S-Triazolo[3,4-b] [1,3,4]Thiadiazoles.. Chem. Pap., 1999, 53, 215-217.

18. Berkes, D.; Netchitailo, P.; Morel, J.; Decroix, B.: Synthesis of Thieno[b]Quinolizidines and Hofmann Elimination on Methiodides Derivatives.. Synthetic Commun., 1998, 28, 949-956.

17. Berkes, D.; Povazanec, F.; Pronayova, N.: Michael Addition in the Synthesis of Alpha-Aminoacids. Stereoselective Synthesis of Gamma-Aryl-Gamma-Hydroxy-Alpha-Aminobutanoic Acids.. Chem. Listy, 1997, 91, 659-661.

16. Kozisek, J.; Berkes, D.; Decroix, B.: 4,5,6,7,8,9-Hexahydro-10-Hydroxy-5,9-Methano-4H-Thieno[3,2-c]Azonine.. Acta Cryst., 1996, C52, 1825-1826.

15. Berkes, D.; Bar, N.; Decroix, B.: Stereoselective Reduction of New Fused Azoninones With Bridgehead Nitrogen.. J. Heterocyclic Chem., 1995, 32, 403-405.

14. Gomory, J.; Berkes, D.; Mrazkova, J.; Perdoch, V.; Belancik, F.: Ultrazvukovy Chemicky Reaktor Pre Laboratorne Pouzitie.. Chem. Listy, 1995, 89, 594-596.

13. Berkes, D.; Decroix, B.: Synthese De Piperidinethienoazepinones, Methanothienoazecinone Et Etude De Leur Reduction Stereoselective.. Bull. Soc. Chim. France, 1994, 131, 989-991.

12. Safar, P.; Povazanec, F.; Zalibera, L.; Berkes, D.: Simple Preparation of 4,5-Disubstituted -2-Cyclopentenones.. Coll. Czech. Chem. Commun., 1993, 58, 555-564.

11. Berkes, D.; Marunova, E.; Kovac, J.: Substitution of Halogens on Furan by Hydrazines. Stable Derivatives of 5-Hydrazinofurans.. Chem. Papers, 1992, 46, 38-41.

10 . Berkes, D.; Vegh, D.; Dandarova, M.: 1-(5-Nitro-2-Furyl)-2-Propenylation of Aromatic Derivatives Under Friedel-Crafts Conditions.. Chem. Papers, 1992, 46, 333-336.

9. Uher, M.; Berkes, D.; Beno, A.: Haloacetylisothiocyanates in the Synthesis of Fused Furans.. Acta F. R. N. Univ. Commen. - Chimia, 1992, 40, 85-91.

8. Uher, M.; Berkes, D.; Konecny, V.; Beno, A.: Chlorinated Derivatives of N-Phenyl-N?-Chloroacetylthiourea.. Acta F. R. N. Univ. Commen. - Chimia, 1992, 40, 67-76.

7. Berkes, D.; Vegh, D.; Kovac, J.: Sposob pripravy substituovanych 3-heteroaroyl-2,3-dibrompropanovych kyselin., 1990, CZ-Pat 260336.

6. Berkes D.;Kacina R.;Gomory J.;Frankova M.;Niznansky J.: Sposob pripravy 1-bromdodekanu., 1990, CZ-Pat 270876.

5. Berkes, D.; Kovac, J.: Reactions of Substituted 2-(2-Furyl)-1,2,2-Ethylnetricarbonitriles With Primary and Secondary Amines.. Chem. Papers, 1989, 43, 579-588.

4. Stasko, A.; Berkes, D.; Biskupic, S.; Pelikan, P.; Polakovic, J.: Ion Radical of Substituted 2-Furylethenetricarbonitriles (an ESR, Quantum Chemical, and Electrochemical Study).. Chem. Papers, 1989, 43, 177-190.

3. Berkes, D.; Kovac, J.: 3-(5-halogen-2-furyl)-3-kyano-2-substituovane derivaty kyseliny propenovej a sposob ich pripravy., 1989, CZ-Pat 254207.

2. Berkes, D.; Kovac, J.: 5-Tricyanovinyl-2-Furylation of Aromatic Derivatives.. Coll. Czech. Chem. Commun., 1989, 51, 1450-1454.

1. Uher, M.; Berkes, D.; Lesko, J.; Floch, L.: Reactions of Carbonyl Isothiocyanates With Nucleophilic Bifunctional Reagents.. Coll. Czech. Chem. Commun., 1983, 48, 1651-1658.

 

Structured CV:

2002 - presents

Slovak University of Technology, Bratislava, Slovakia

Associate professor of Chemistry

 

1990 - presents

Slovak University of Technology, Bratislava, Slovakia

Head of University Laboratory in pharmaceutical company Zentiva Ltd. Hlohovec

 

1987 - 2001

Slovak University of Technology, Bratislava, Slovakia

Assistent professor of Organic Chemistry

 

1992 - 1993

Post-doctoral research with Professor J. Morel  Universite du Havre, France

 

1988 - 1989

Post-doctoral research with Professor E. Henry-Basch, University Paris Sud in Orsay, France

 

1982 - 1987

PhD. (with Professor J. Kovac) Slovak Technical University of Bratislava

 

1976 - 1981

Ing. Chemistry, first class, Slovak Technical University of Bratislava

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