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Laboratory of Synthetic Organic Chemistry

Laboratory of Synthetic Organic Chemistry is continuing the tradition of the former Laboratory of Synthetic and Physical Organic Chemistry dealing with the chemistry of cage molecules. Research in the laboratory is concerned with the synthesis of cage molecules, study of the reaction mechanisms performed on cage molecules, as well as the use of cage molecules as building blocks in constructions of supramolecular assemblies. Covering various synthetic, analytical and spectroscopic techniques on a wide range of substrates, the research activities in the laboratory are ideal for training young researchers in graduate and post-graduate education (BSc, MSc, and PhD thesis).

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   Laboratory of Synthetic Organic Chemistry is continuing the tradition of the former Laboratory of Synthetic and Physical Organic Chemistry dealing with the chemistry of cage molecules. Research in the laboratory is concerned with the synthesis of cage molecules, study of the reaction mechanisms performed on cage molecules, as well as the use of cage molecules as building blocks in constructions of supramolecular assemblies. Covering various synthetic, analytical and spectroscopic techniques on a wide range of substrates, the research activities in the laboratory are ideal for training young researchers in graduate and post-graduate education (BSc, MSc, and PhD thesis).

Research activities of the Laboratory of Synthetic Organic Chemistry cover a broad spectrum of studies, primarily in the field of synthetic organic chemistry, but also photochemistry, supramolecular chemistry and physical organic chemistry. The most significant part of our work is related to the development and application of new methods and techniques in the synthesis of polycarbocyclic molecules, as well as towards incorporation of these molecules in the more complex molecular structures and assemblies.

    Our previous work was synthesis and chemistry of strained polycyclic cage compounds, particularly the [3.1.1]propellane and other molecules possessing the "atetrahedral" carbon atoms. We work also on the synthesis and chemistry of polycyclic compounds containing "planar and/or pyramidal" carbon atom or the strained carbon-carbon bonds (J. Phys. Org. Chem.2008, 21, 299-305). As a part of our interest in bonding between carbon atoms, the chemistry of strained-rings is undertaken in detail.

  

One area of investigation in our group includes the synthesis of novel macrocyclic host systems such as adamantane or PCU-functionalized crown ethers, aza- and thia-crown ethers, as well as some cryptand-like molecules. The macrocyclic compounds of this type are of interest as host molecules for metal ions. Incorporation of lipophylic cage compounds in the macrocyclic skeleton results in better solubility of the host molecules in organic solvents and potential applicability of these molecules as cation extracting agents.

   Recently we have prepared series of thialactones that form tubular assemblies governed by CH×××O hydrogen bonding between the stacked rings. These are the first columnar structures of polythialactone systems reported.

 

Furthermore, we have prepared a novel adamantane thialactones and studied their ability to complex heavy and transition metal cations. The results are compared with those obtained with similar thiamacrocyclic ligands which have flexible chain of methylene groups incorporated into the macrocyclic framework. The results showed that the most of the hosts studied are very good in complexing the Ag+ ion. The formation of complexes has also been demonstrated using NMR titration experiments for macrocycles 13 and 14 with AgTFA.(J. Org. Chem. 2008, 73, 9221-9227).

 

We are also interested in the incorporation of adamantane skeleton into unnatural derivatives of amino and hydroxy acids, which are transformed to peptidomimetics. We showed that incorporation of unnatural amino acids derived from adamantanes in the methionin-enkephalin peptide increased lipophilicity of the pepetide, and in that way, increased the transport through the cell membrane. These derivatives showed good in vitro anticancer properties and are therefore the promising candidates for the development of new anticancer agents (J. Med. Chem.2006, 49, 3136-3142).

   A special interest has been directed towards synthesis of cyclic peptides, depsipeptides (J. Mol. Struct.2007,832,191-198;J. Mol. Struct.2008,888,238-243) and retropeptides (Tetrahedron,2007,63,7985-7996;J. Mol. Struct.2008,876, 218-224) which contain unnatural amino acids.

 

 

   Besides biological activity, these compounds are expected to show good properties in solid state, forming tubular structures or ion channels (Tetrahedron 2007, 63, 7985-7996).

 

 

In addition to the synthesis of macrocyclic host molecules with the incorporated cage molecules as potential hosts for metal ions, we are also interested in the synthesis of anion binding agents. The polycyclic molecules are therefore functionalized by groups capable of forming hydrogen bonds with anions, such as pyrrole (Tetrahedron Lett. 2007, 48 , 7873-7877), amides and ureas.

 

   Recently, we have prepared and studied the anion binding ability of sterically congested adamantine-calix[4]pyrroles and adamantine-calixphirins.

  

Whereas calixphirin 9 does not bind anions, analogus calix[4]pyrrole 8 forms a complex with Clˉ  in the DMSO solution and in the solid state. The solid state complexation has been accomplished on grinding in a mill, wich is the first example of complex formation with an anion in the solid state (Tetrahedron, 2009,u tisku0040-4020).

   A part of the research in the group is oriented towards using photochemistry as a key step in the transformation of adamantane and PCU derivatives into more complex polycyclic molecules, the potential antiviral and anticancer agents. For that purpose, cage molecules are functionalized with the phthalimide chromophores.

 

   Adamantyl-functionalized phtalimides were synthesized and the probability of intramolecular photochemical hydrogen abstraction in the solid-state analyzed by x-ray cristallographic analyses (Tetrahedron, 2009, 65, 1438-1443).

 

   Furthermore, we have prepared a novel 2,4-methanoadamantene-benzazepine by a domino photochemistry of N-(1-adamantyl)phtalimide (Org. Lett. 2008, 10, 3965-3968).

  

   Mechanistic studies of the photochemical reactions are undertaken in collaboration with the research group of Professor A. G. Griesbeck, PhD (University of Cologne, Germany) and Dr. H. Görner (Max-Planck-Institute für Bioanorganische Chemie, Mülheim).

Nikola Basarić

+385 1 456 1141

Vesna Blažek
PhD

senior assistant
+385 1 456 1141

Kata Majerski
prof. dr.

senior scientist
+385 1 468 0196

Marina Šekutor
Ph.D.

postdoctoral assistant
+385 1 456 1165

Antonela Šimunić

+385 1 456 1002

Đani Škalamera
MChem

+385 1 456 1165

Tatjana Šumanovac Ramljak
Ph.D.

assistant
+385 1 456 1165

Cage Compounds: Building Blocks for Molecular Architecture

Principal Investigator: Kata Majerski

Cage compounds are characterized by three-dimensional structures which have defined rigid geometry and as such, they are very useful synthons in organic synthesis, as well as the indispensable substrates for the mechanistic studies. Moreover, the various atomic positions in a cage can serve as branching points where the additional ligating group can be introduced. These substituted derivatives can be used as building blocks in supramolecular chemistry. The first step towards employing cage compounds in the synthesis of more complex molecular systems is the understanding of their reactions.

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Photochemistry of polycyclic molecules: From mechanistic studies to new drugs and medicinal applications

Principal Investigator: Nikola Basarić

 

HRZZ

Photons are phenomenal reagents which open new opportunities in chemical synthesis that cannot be attained in the chemistry of ground state. The goal of the project was to find new photochemical transformations applicable in organic synthesis, as well as investigation of the photochemical reaction mechanisms. In addition, the aim of the project was to go beyond the state of the art, and ultimately find application of photochemistry in new medical treatments and synthesis of new compounds, potential drug molecules for treating malignant diseases.

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