In our investigations within the 5th FP project InkCor, EVKA4-CT-2001-00049 (coordinator J. Kolar) we were interested in the inhibition of iron-gall-ink corrosion. The result of this investigation was an international patent application (in 2005); in 2010 the EU patent was assigned to this application. In our laboratory two target compounds (myo-inositol phosphates) were prepared; they were shown to prevent iron-gall-ink decay in cellulose items at the same level as phytic acid dodecasodium salt. As such they can serve as a tool for the paper documents stabilisation.
F.32 International patent
COBISS.SI-ID: 26939909Our patent reports on the analogues of 1,3-bis(4-nitrophenyl)triazenes, their pharmaceutically acceptable salts and N-acyl derivatives as new agents for the treatment of different types of tumors. The described compounds show cytotoxicity at very low concentrations, they are 300-600-times more efficient than up-to now most efficient triazene derivative berenil. They are in fact 4-nitro-1,3-diaryltriazenes that possess two additional electron-withdrawing groups and are highly cytotoxic compounds. Their acylation at the triazene nitrogen increases the solubility. Furthermore, N-acyltriazenes can be considered as prodrugs of their non-acylated analogues. The antiproliferative activity of new compounds also depends on the type of the substituent introduced at the ortho position of the two benzene rings. It turned out that trifluoromethyl substituent increased cytotoxicity of the compound more than other groups. This patent is a result of our cooperation with the research group of Dr. Maja Osmak (Institut Ruđer Bošković, Zagreb) based upon the long-term agreement between our institutions.
F.32 International patent
COBISS.SI-ID: 30639621The patent describes the synthesis of key intermediates for the synthesis of rosuvastatin and their pharmaceutically acceptable salts. The patent is a successful finish of one of the joint projects between the Project Leader and Lek Pharmaceuticals on the synthesis of statins. In this joint research work we developed a completely new methodology for the preparation of the above mentioned drug. The chemistry is based on a new principle via a lactone intermediate and represents a new convergent route, which is also free of any steps requiring cryogenic conditions. It is superior to other methods for the preparation of statins as it is truly efficient, economically and environmentally acceptable on both laboratory and industrial scale. This is an exemplary case of transfer of knowledge into and from the industry. It is worth mentioning that in Slovenia Lek Pharmaceuticals first launched generic rosuvastatin, called “Coupet”. The result of the above mentioned collaboration is also scientific publication “Lactone Pathway to Statins Utilizing the Wittig Reaction. The Synthesis of Rosuvastatin”, authored by Z. Časar, M. Steinbücher, J. Košmrlj in J. Org. Chem. 2010, 75, 6681–6684. This article was listed among the journal's top "20 most read articles in October 2010" and highlighted in “Highlights from the Literature” in Organic Process Research & Development 2010, 14, 1276–1286.
F.32 International patent
COBISS.SI-ID: 34323205On the invitation from the editorial board, J. Košmrlj as a Volume Editor prepared book entitled ’Click Triazoles’, published within the Springer series Topics in Heterocyclic Chemistry. This invitation is recognition to our research work in the field of heterocyclic chemistry. Additional recognition and acknowledgement is demonstrated by positive reply of leading scientists in the field to contribute their chapters. These include: 1) Semin Lee, Amar H. Flood, Indiana University, Bloomington, USA. Binding Anions in Rigid and Reconfigurable Triazole Receptors. 2) Hak-Fun Chow, Chui-Man Lo, and Yuan Chen, Center of Novel Functional Molecules, and Institute of Molecular Functional Materials and The Chinese University of Hong Kong, China. Triazole-Based Polymer Gels. 3) James D. Crowley and David A. McMorran, University of Otago, New Zealand. "Click-triazole" coordination chemistry: Exploiting 1,4-disubstituted-1,2,3-triazoles as ligands. 4) S. Mignani, Y. Zhou, T. Lecourt, L. Micouin, Université Paris Descartes, France. Recent developments in the synthesis 1,4,5-trisubstituted triazoles. 5) Michael Watkinson, Queen Mary University of London, UK. Click triazoles as chemosensors. 6) Tianqing Zheng, Sara Rouhanifard, Abubakar Jalloh, Peng Wu, Albert Einstein College of Medicine, Yeshiva University, USA. Click Triazoles for Bioconjugation. 7) Benjamin R. Buckley and Harry Heaney, Loughborough University, UK. Mechanistic Investigations of Copper(I) Catalysed Alkyne-Azide Cycloaddition Reactions.
C.01 Editorial board of a foreign/international collection of papers/book
COBISS.SI-ID: 36164101Programme group members caried out (besides title lecture) a series of plenary and invited lectures at international and domestic conferences and universities or other institutions. Plenary lectures: (1) M. Kočevar: Microwave-assisted catalyzed organic transformations, 9th International Symposium of the Romanian Catalysis Society, 2010, Iasi, Romania. (2) M. Kočevar: 2H-Pyran-2-ones and fused pyran-2-ones as useful building blocks in medicinal chemistry, 38. konference Syntéza a analýza léčiv, pořádaná při přiležitosti 40. výroči založení Farmaceutické fakulty UK v Hradci Králové, 2009, Hradec Králové, Czech Republic. (3) M. Kočevar: Selective organic synthesis: from conventional reaction conditions to green chemistry, Catalysis in organic chemistry Workshop, 2009, Bucharest, Romania. (4) S. Polanc: Various applications of nitrogen-containing molecules in organic synthesis, 2010, 48th Meeting of the Serbian Chemical Society, Novi Sad, Serbia. (5) S. Polanc: Chemistry and biological potential of diazenes and analogues, 2011, 40th Conference drug synthesis and analysis, Brno, Czech Republic. Selected invited lectures at conferences: (6) M. Krivec, J. Hren, A. Berkessel, M. Kočevar: Synthesis and desymmetrization of prochiral bicyclo[2.2.2]octene derivatives. 6th Organocatalysis COST - meeting CM0905, May 2014, Palermo, Italy. (7) K. Kranjc, M. Kočevar: Regio- and stereoselectivity of cycloadditions of 2H-pyran-2-one derivatives. Florida Heterocyclic and Synthetic Conference, 2012, Gainesville, U.S.A. (8) G. Strle, J. Cerkovnik: Preparation of substrates for the synthesis of dihydrogen trioxide (HOOOH). Second ORCA Summit, COST, 2012, Aix-Marseille, France. (9) M. Kočevar: Pyran-2-ones as synthons in organic synthesis. ORCA summit, COST, 2011, Berlin, Germany. (10) K. Kranjc, M. Kočevar: Recent advances in the application of 2H-pyran-2-ones as dienes in various environmentally benign cycloadditions: syntheses of indoles, anilines, biphenyls, bicyclo[2.2.2]octenes and other adducts. 13th Blue Danube Symposium on Heterocyclic Chemistry, 2009, Bled; Slovenia. (11) N. Maraš, M. Kočevar: Direct cyclocondensation of carboxylic acids with 1,2-diaminobenzenes to benzimidazoles employing boric acid catalysis. Symposium International de Chimie Hétérocyclique, 2011, Fès, Morocco. (12) M. Gazvoda, B. Burja, M. Kočevar, S. Polanc: Biological activity of pyrazolones and their precursors synthesised via diazenes. 14th Conference on Heterocycles in Bio-organic Chemistry, 2011, Brno, Czech Republic. (13) K. Kranjc: Cycloadditions of 2H-pyran-2-ones and fused analogues under green reaction conditions. Catalysis in organic chemistry, Workshop, 2009, Bucharest, Romania. Invited lectures at universities and other institutions: (14) S. Polanc: Several adventures associated with C-N bond formation, 2009, University of Buenos Aires, Argentina. (15) F. Požgan: Pyran-2-one derivatives as building blocks for a variety of heterocyclic compounds, 2009, University of Sarajevo, Bosnia and Herzegovina. (16) F. Požgan: Transition-metal-catalyzed selective carbon-carbon bond formations, 2012, University of Sarajevo, Bosnia and Herzegovina. (17) B. Štefane: Olefin metathesis as an industrial synthetic step: yes or no? 2012, University of Sarajevo, Bosnia and Herzegovina. (18) M. Kočevar: Transformations of 2H-pyran-2-ones and their fused systems, Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 2012, Budapest, Hungary. (19) K. Kranjc: A multitude of reaction pathways starting from 2H-pyran-2-ones and their fused derivatives, 2014, J. J. Strossmayer University, Osijek, Croatia. (20) K. Kranjc: Asymmetric vs. symmetric bicyclo[2.2.2]octenes prepared with cycloadditions of 2H-pyran-2-ones, 2013, East China Normal University, Shanghai, China. 21. K. Kranjc: 2H-Pyran-2-ones and their fused derivatives as dienes in Diels-Alder reactions, 2012, East China Normal University, Shanghai, China. (22) J. Košmrlj: Explori
B.04 Guest lecture
COBISS.SI-ID: 34178053