| Abstract [eng] |
Pyridine ring bearing compounds are found in many natural products, active pharmaceuticals and functional materials. According MDL Drug Data Report pyridine fragment is the most abundant heterocyclic fragment found in the drug molecules and is present in more than 7000 existing drugs. Bipyridine and terpyridine carcasses are well known for their chelating ability, which is exploited in many fields including enantioselective catalysis and chemotherapy. 1,4-Dihydropyridine can be used as core fragment for fluorescent sensors. Pyridine ring is also used as electron acceptor for electron transfer in organic light emitting diodes. The aim of this work is the a development of synthetic methods for 5-hydroxyomeprazole, bromocyclopropylpyridines, orelanine and terpyridine building blocks. The existing methods for each of the target system have many flaws and the 5-hydroxyomeprazole has no synthetic method at all. There was a chemical synthesis pathway for 5-hydroxyomeprazole developed. It was found that methyl 2,4-dichloro-5,6-dimethylpyridine-3-carboxylate reaction with two equivalents of sodium methoxide product distribution depends on reaction temperature. The procedure for regeneration this reaction side products to the starting compound was developed. It was found that during hydrodehalogenation reaction of 2-chloro-5,6-dimethyl-4-methoxypyridine-3-carboxylate under 80 atmospheres pressure, the hydrolysis of 4-methoxy group occurs. Non-aqueous Sandmeyer reaction conditions for bromo(chloro)cyclopropylpyridines were developed. It was found that Sandmeyer reaction of aminocyclopyridines with copper(II) bromide and alkylnitrite undergoes both cationic and radiacal pathway. 2-pyridinediazonium ion formed upon reaction of 2-amino-5-cyclopropylpyridine is apparently unstable in rather polar solvents and undergoes heterolytic cleavage. The produced highly reactive cation reacts with any available nucleophile. Unpublished formation of ω-halogenoalcoxypyridines was observed. Novel improved total synthesis of orelanine was developed. For this synthesis novel an efficient aqueous synthetic pathway for 3,4-dimethoxypyridine was applied and transition metal catalysis free 3,4-dimethoxypyridine C-C homocoupling method was developed. Synthesis of ,6''-bis(bromomethyl)-4'-(4-nitrophenyl)-2,2':6',2''-terpyridine utilizing Kröhnke pyridine synthesis method was developed. |
