Date of Award

12-31-2015

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry/Organic Chemistry

First Advisor

Béla Török

Second Advisor

Manickam Sugumaran

Third Advisor

Marianna Török

Abstract

Heterocyclic compounds possess a wide range of biological properties such as antibacterial, antiviral and antitumor activities. Organic chemists have developed synthetic methods of heterocycles because of their interesting features. Despite the previous known methods, new synthetic pathways were developed in order to comply with environmental regulations and safety concerns. The design of environmentally benign processes with the aid of microwave activation, aluminum-nickel alloy, K-10 montmorillonite and water as a solvent and as reaction tools, was the major aim of this work.

Initially, the reduction of indoles and quinolines is described using water as a hydrogen source. The method is based on the application of a RANEY® type Ni–Al alloy in an aqueous medium. The presonication of the alloy was carried out before performing each reaction. The simplicity and efficacy of the method are illustrated by the selective reduction of a variety of substituted indoles and quinolines to indolines and tetrahydroquinolines, respectively. The scope of the application of Ni-Al alloy was extended to the debenzylation of a variety of N- and O-benzylated compounds. The 1h presonicaiton of alloy is enabled the debenzylation to occur efficiently. Then, the energy consumption of six different types of K-10 montmorillonite catalyzed heterocycle synthesis reactions were performed under microwave irradiation and conventional heating with multiple substrates and varied experimental parameters.

In the majority of the studied reactions, the microwave-assisted method appeared to be more energy efficient by various extents than conventional heating. Also, a variety of pyrrole analogues were synthesized with a sustainable pathway. The reactions were carried out under the ultimate green conditions excluding both catalyst and solvent applying simple stirring at room temperature. The focus of the next two projects was on the synthesis and medicinal chemistry application of biologically active compounds. A new class of Phospholipase D (PLD) inhibitors, based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure, is synthesized in a four-step sequence of reactions and the products were tested for biological activities. Multiple compounds exhibited inhibition of PLD activity in the low nanomolar to low micromolar IC50 range. Also, Sulfonamide linker-based inhibitors with extended linear structure were designed and synthesized with the aim of producing multifunctional agents against several processes involved in the pathology of Alzheimer’s Disease.

Comments

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