Group of Synthesis and Chemical Transformations of Coumarins
Department of Organic chemistry
Head of laboratory: Assoc. Prof. Rositca D. Nikolova, Dr.
Team Members: Assoc. Prof. Dr. Rositca Nikolova, Head Assist. Prof. Dr. Nevena Petkova, PhD Student Eleonora Ilieva & co-workers:
The group has experience in synthesis, modification and investigation the reactivity of coumarin derivatives and their phosphorous-containing analogues towards nucleophilic reagents including organomagnesium and organozinc compounds. As a result of our research in this direction we synthesized and characterized more than 250 new organic compounds. Due to the complex reaction routes applied in the synthesis and modification of the coumarin derivatives and analogues we paid special attention to the influence of the reaction conditions on the yield and selectivity of the process. In this connection we also investigated the mechanism of the different transformations by means of both synthetic and quantum-chemical methods. The understanding of the mechanism of the processes allowed us to optimise the reaction conditions in order to obtain pure products with high yield. In our experiments we apply one-pot approach for processes with consecutive reaction steps or use ultrasound treatment in order to achieve more economic (in terms of materials and energy) procedures. Some of the compounds synthesized up to now in our laboratory represent a new class of heterocyclic compounds and the synthetic methods for their preparation, developed by us, are published in Houben-Weyl Methods of Molecular Transformations. The group has taken part in 12 successfully finished and 4 running research projects supported by the National Science Fund (Bulgaria) and the University Research Fund of the University of Sofia and one bilateral project, as well as the pharmaceutical companies Bayer, BioSpecs, and DuPont.
- R. D. Nikolova, A.G. Bojilova, N.A. Rodios; A new and efficient method for conjugate addition of trialkylphosphites to 3-acylsubsituted coumarins; Tetrahedron 60, 10335 (2004).
- N. I. Petkova, R. D. Nikolova, A. G. Bojilova, N. A. Rodios, J. Kopf, Synthesis of heterocyclic methylenebisphoshponates by 1,3-dipolar cycloaddition of ethyl diazoacetate to 1,2-benzoxaphosphorin-3-phosphonates, Tetrahedron, 65, 1639 (2009).
The coumarin phosphorus-containing derivatives are nowadays well known to exhibit various biological activities, to be extensively used in the medicine, as pesticides etc. The specific properties of these compounds are due to the two functional groups in their structure and the unique combination of different characteristics of both groups. Phosphorous-containing coumarins are able to form complexes which are of significant importance for their application in medicine. Despite of the numerous publications concerning the methods for synthesis and analysis of 3-substituted 2-oxo-2H-1-benzopyrans (coumarins) containing electron-acceptor group, the chemical behavior and properties of phosphorus-containing coumarins are not very well studied. By this reason in the last few years our research efforts have been directed mainly towards the synthesis of phosphorous-containing coumarin derivatives and detailed investigation of their chemical behavior and properties. We developed a synthetic method for preparation of the phosphorus-containing coumarin derivatives and via interaction of salicylaldehyde with triethylphosphonoacetate Knoevenagel reaction conditions. In order to synthesize new phosphorus-containing coumarin derivatives we thoroughly investigated the interaction of both the brome derivatives of coumarin with phosphites.
Having in mind the potential biological activity of the target coumarin derivatives, tested for biological activity were performed for a series of compounds and most of the representatives were found to possess relatively high activity as growth regulators.
Plans for future development of the synthetic work
The main goal of the our future investigations is directed towards understanding the chemistry of phosphorous-containing coumarin derivatives and analogues, and development of new synthetic routes for preparation of new bi- and poly-functional compounds based on these reagents. With this goal our interest focuses on several objectives:
- comparison between phosphorous-containing coumarin derivatives and other 3-substituted coumarins as special attention will be paid to their behavior in different reactions and their bioactive and optical properties;
- clarification of the influence of the substituting group on the optical properties and the biological activity of the studied class of organic compounds;
- determination of the mechanisms of the reaction routes applied for synthesis and modification of the target compounds;
- synthesis of new types of compounds containing functional groups that are known to possess specific biological and pharmaceutical activity or luminescent and fluorescent properties;
- determination of specific types of biological activity;
- development of preparative methods for the compounds suitable for multidisciplinary application.