Development of a synthetic methodology for thienopyridinone and thienodiazepinone derivatives and benzimidazo-oxazepines

Korkmaz Çokol, Nalan
Thienopyridinone and thienodiazepinone derivatives are known for their diverse pharmacological activities. Pyridinones and diazepinones play an important role in inhibition of some enzymes such as glycogen synthase kinase-3β and regulation of various cell functions. They also demonstrate an interesting property in the repair of damaged DNA. In the first part of this thesis, we synthesized thienopyridinone and thienodiazepinone derivatives. Aminothiophene derivatives were successfully synthesized via Gewald type reaction which was followed by the conversion to iodo- and bromo-thiophene derivatives via modified Sandmayer reaction. Sonogashira cross-coupling reaction was used to generate carbon-carbon single bond between the thiophene ring and alkyne derivatives. Cyclization of those compounds with hydrazine hydrate gave target molecules. Imidazole derivatives exhibit a wide range of bioactivities, therefore they are of intensive synthetic interest. They are also used as precursors for the synthesis of heterocycles having pharmaceutical properties. In the second part of this thesis, a concise and efficient approach to the synthesis of benzimidazo-oxazepine derivatives was developed. The synthetic strategy relies on the O-propargylation of salicyl aldehyde derivatives followed by Sonogashira cross-coupling reaction for further derivatization. Resulting alkyne derivatives were converted into the corresponding imidazole rings under acidic condition. NaH-mediated cyclization gave desired compounds, benzimidazo-oxazepines.


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Biosensor construction and characterization studies of poly(acrylic acid) (PAA) and poly(1-vinyl imidazole) (PVI) complex systems have been carried out. The biosensors were prepared by mixing PAA with PVI at several stoichiometric ratios, x (molar ratio of the monomer repeat units). The enzyme, invertase, was entrapped in the PAA/PVA interpenetrating polymer networks during complexation. Modifications were made on the PAA/PVI conducting polymer electrolyte matrixes to improve the stability and performance o...
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The tetramethyl and tetra-tert-butyl derivatives of cyclobutadiene and tetrahedrane have been studied with ab initio and density functional methods. The ring in tetra-tert-butylcyclobutadiene displays very unequal bond lengths (1.354, 1.608 Angstrom) and confirms the earlier suspicion that the low-temperature X-ray structure was distorted. The C-C single bonds have the longest separations found to date between sp(2)-hybridized carbons. Tetra-rert-butyltetrahedrane, which prefers T over Td symmetry, is calcu...
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With the aim of achieving new compounds possessing both anti-inflammatory and antiplatelet activities, we synthesized (E)-3-[3-(pyridin-3/4-yl)-1-(phenyl/sulfonylmethylphenyl)-1H-pyrazol-4-yl]acrylamides, and evaluated their COX-1 and COX-2 inhibitory and antiplatelet activities. Since COX-2 inhibitory and antiplatelet compounds have anticancer potential, we also screened their antiproliferative effects against three human cancer cell lines. Compounds 5n, 5p, 5s, 10d, 10g and 10i were determined as dual COX...
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A family of chiral bifunctional acid-/base-type quinine/squaramide organocatalysts is shown to be highly active promoters of the conjugate addition of 1-nitropropane to various trans-β-nitroalkenes. The cooperation of the quinine and the sterically encumbered squaramide moieties catalyzed the Michael addition reactions at 0 °C by using a catalyst loading of only 2 mol % to afford the 1,3-dinitro Michael adducts with excellent enantioselectivity and diastereoselectivity (up to 95 % ee and syn/anti isomers
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For the synthesis of bromo-conduritol-B skeleton, bromo-1,4-benzoquinone was subjected to bromination followed by the reduction of the carbonyl groups with NaBH4. Substitution of bromides bonded to sp(3)-hybridized carbon atoms with AgOAc gave the bromo-concluritol-B tetraacetate in high yield. For the construction of bromo-conduritol-C skeleton, 2,2-dimethyl-3a,7a-dihydro-1,3-benzodioxole was used as the starting material. Photooxygenation of the diene unit gave an unsaturated bicyclic endoperoxide. Bromin...
Citation Formats
N. Korkmaz Çokol, “Development of a synthetic methodology for thienopyridinone and thienodiazepinone derivatives and benzimidazo-oxazepines,” Ph.D. - Doctoral Program, Middle East Technical University, 2018.