Projects / Programmes
Organic Chemistry: Synthesis, Structure, and Application
January 1, 2015
- December 31, 2021
| Code |
Science |
Field |
Subfield |
| 1.04.00 |
Natural sciences and mathematics |
Chemistry |
|
| Code |
Science |
Field |
| P390 |
Natural sciences and mathematics |
Organic chemistry |
| Code |
Science |
Field |
| 1.04 |
Natural Sciences |
Chemical sciences |
Synthesis; catalysis; oxidation; reduction; cycloaddition; desymmetrization; C-C, C-N bond formation; transition metal, hydrogen trioxide; ozone; singlet oxygen; organometallic compounds; gramine; thalidomide; bicyclo/2.2.2/octene; molecular probe; fluorescence; neurodegenerative diseases; FDDNP-PET
Researchers (26)
Organisations (1)
Abstract
Discovery of novel methods and processes in the chemical synthesis, especially those with high atom economy and environmental sustainability, is indispensable in identifying new compounds that are of prime importance in the fields of material and medicinal sciences. The primary objective of this research proposal is developing highly efficient state-of-the-art chemical methods, including organo- and transition metal catalysis, and biomedical applications. Based on our expertise in the synthesis, we propose to focus on the research topics as follows.
1) Based on our communication on facile entry to pyridyl 1,2,3-triazolium cations 1 (Fig. 1, Supporting Information) [Org. Lett. 2013, 15, 5084], we will explore the scope of these compounds as N^C bidentate pyridyl-triazole N-heterocyclic carbene (Py-trzNHC) ligands for transition metals to form complexes 2. Attention will be focused on complexes 2 with Cu, Ru, Ir, Os, Pd and Pt. With the primary objective of our research being on exploring the utility of Py-trzNHC in catalysis and biochemistry, the potential of 2 will be examined as catalysts for oxidations, reductions, C–C and C–N bond formation reactions, and others. Selected compounds will be screened for anti-tumor and anti-bacterial activity.
2) Our discovery of methyltrioxorhenium(VII) (MTO) catalyzed transformation of hydrotrioxides into HOOOH [J. Am. Chem. Soc. 2008, 130, 14086; Chem. Rev. 2013, 113, 7930] will enable us to study the chemistry of this polyoxide in more detail. In particular, we will examine MTO-catalyzed addition of HOOOH to ketones and selective low-temperature oxidations of organic substrates with HOOOH. The mechanism of these reactions as well as the reaction of HOOOH with ozone, singlet oxygen and superoxide anion will be studied in detail. We will also study the insertion of ozone into the RM–H bond (M=metal) and the chemistry of the intermediates formed thereof.
3) Having expertise in the field of Diels–Alder reaction of (fused)pyran-2-ones forming bicyclo[2.2.2]octenes [J. Org. Chem. 2009, 74, 6303; J. Org. Chem. 2012, 77, 2857], compounds 3a will be examined as precursors for symmetric tetraesters [Eur. J. Org. Chem. 2011, 3368] and tetraacids 3b of different exo,endo-structures and further transformed to the corresponding tetraol derivatives 3c (Fig. 2). The prochiral 3a–c will be subjected to desymmetrization under (organo)catalytic conditions, e.g. into 3d.
4) Since our initial discovery of FDDNP (Fig. 3) and its successful application with positron emission tomography (PET) as a molecular probe for non-destructive diagnosis of Alzheimer’s disease [Acc. Chem. Res. 2009, 42, 842], we attempted to improve the probe’s ability to label protein aggregates [Proc. Natl. Acad. Sci. U.S.A. 2012, 109, 16492]. Now we will modify the structure of the lead compound to extend the distance between the donor and acceptor groups and introduce heteroatoms in the aromatic ring to promote binding interactions with protein aggregates.
Significance for science
The proposed project will contribute new knowledge in the most important fields of chemistry, namely, organic synthesis, medicinal chemistry and catalysis (homogeneous and heterogeneous catalysis; transition metal catalyzed reactions; organocatalysis; enantioselective catalysis). Based on our extensive expertise in organic synthesis, we will continue developing green chemistry methods aiming at the protection of our environment (green media, microwave-assisted technique, high pressure up to 20 kbar, etc.). We plan to search for novel, potentially recyclable catalytic systems that will enable efficient functional group transformations with high selectivity and will potentially allow the reactions to be conducted in environmentally benign solvents (including water), without the need of special precautions. Novel types of building blocks will be prepared and novel techniques for the synthesis including enantioselective synthesis will be developed. Additionally, novel reactions in organic synthesis will be clarified, and novel types of biologically active compounds will be prepared. The obtained data and knowledge on the synthesis, structure and reactivity of prepared compounds and catalysts are of primary interest for fundamental sciences, for atmospheric and environmental chemistry as well as for biology and medicine. Furthermore, the proposed work on the synthesis, characterization, and application of new molecular probes for medical research promises new tools for medical research and diagnostics and will explain basic processes, leading to neurological diseases.
Significance for the country
Developing new knowledge (novel methods, catalysts, intermediates, and novel useful compounds) is extremely important for Slovenia in order to protect our environment and in order to help our industry to get acquainted with the progress in the basic research work and also in the development of green applications for industrial purposes. In particular, this knowledge, which is in Slovenia still at intermediate level, will be improved and brought to Slovenian companies. Namely, students that are going to participate in the research will probably find their positions in the pharmaceutical and also other companies, where such knowledge is more and more indispensable. Our broad connections with the research teams from all over the world will enable developing multidisciplinary knowledge and methods to educate our students and younger researchers via international grants in close contacts with the best research teams around the world. The invitations for plenary and other lectures at important international conferences, universities and institutes are very important for the promotion of Slovenian science. Similarly, we promote Slovenia by memberships in the Management Committees and working groups within COST programmes, bilateral and other programmes, by attracting foreign researchers and Ph. D. students, by memberships in editorial boards of journals, etc.
Our research work is tightly embedded within the existing institutional and especially within national or international research and development programmes and projects. We strictly follow priorities of the Slovenian and international research by developing new materials, novel industrial procedures and tools or their optimizations via contracts with industry. Since we are a group with a broad expertise of knowledge, we are developing highly interdisciplinary methods that may find in the future broad application in our industrial companies. A part of our research programmes is tightly connected with industrial needs, for example developing industrially relevant reactions (green catalysis, etc.) and products (for example rosuvastatin that was developed in cooperation with Lek/Sandoz or potential FabF and FabH inhibitors as well as other internationally patented products (see 14.1, 14.2 and 14.4) including developing new neuroimaging probes for medical research and diagnostics as was developed in cooperation with the Department of Medical and Molecular Pharmacology at the UCLA, U.S.A. and by our colleagues from the Faculty of Medicine at the University of Ljubljana).
Being a part of a teaching institution, our expertise will enable us to educate students in mastering standard and specialized operations to be applied in an academic setting and also in situations they face in an industrial environment.
Most important scientific results
Annual report
2015,
interim report
Most important socioeconomically and culturally relevant results
Annual report
2015,
interim report
