Master Degree / Yüksek Lisans Tezleri
Permanent URI for this collectionhttps://hdl.handle.net/11147/3008
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Master Thesis Synthesis of 1,5-Disubstituted 1,2,3-Triazole Modified Azacoumarins(01. Izmir Institute of Technology, 2022) Çağır, Ali; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyCancer is a deadly disease that threatens human health and all life, and it is still a serious problem despite all scientific studies for more than half a century. Pharmacophores are a part of the structure of a drug (or drug candidate) responsible from the biological activity. This thesis is related with the synthesis of novel compounds having two well-known pharmacophore structures, 1,2,3-triazole and 1-azacoumarin. Both structures can be found in the structure of many biologically active molecules. Triazole modified coumarin derivatives are scarce in the literature. In this study, we aimed to improve the synthetic route toward the synthesis of 1- azacoumarin derivative modified by 1,2,3-triazole group at position 4-. Synthesis starts with the conversion of methyl 4-chloroanthranilate to the corresponding 4-OH azacoumarin. Then it is transferred into the 4-OTf group by simply addition of Tf group to OH under basic condition. After Sonogashira reaction and removal of TMS group 4- alkynyl-1-azacoumarin was produced. At this point, conversion of alkyne into 1,5- disubstituted 1,2,3-triazole was examined in the presence of Cp2Ni-Xantphos and RuCl(COD)Cp* catalytic systems but all of trials were failed probably due to the presence of ester group close to the reaction site. In further studies, design of the molecule will be reperformed and ester group will be moved over phenyl rings in order to test its biological activity over cancer cell lines.Master Thesis Synthesis of 1,2,3-Triazole Substituted Azacoumarin Derivatives as Potential Antiproliferative Compounds(01. Izmir Institute of Technology, 2021) Çağır, Ali; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyCancer is one of the deadly diseases that affects millions of people every year and causes death. Although studies toward its treatment are very promising, they are not sufficient. Therefore, the need for new and powerful molecules with less side effects is increasing day by day. 1-Azacoumarin derivatives are molecules whose potential biological activity has just begun to be understood, but not enough research has been done on them. 1,2,3-Triazole structures, on the other hand, are a very important family of molecules in some drugs, whose biological effects have been known for many years. It is known that they have important roles in cancer-preventing mechanisms in various types of cancer. In this study, two different 1,2,3-triazole 1-azacoumarin derivatives were tried to be synthesized. For structure 149, it was aimed to form yinon first and then formation of 1,2,3-triazole was studied but failed. Afterwards, the emphasis was placed on the production of 1-azacoumarin, and then click chemistry experiments were carried out in the presence of copper (I) catalyst. Finally, click chemistry studies were tested in the presence of a nickel catalyst for structure 150. Triazole formation experiments were carried out by click chemistry in the presence of copper catalyst after 1-azacoumarin was obtained.Master Thesis Studies Toward the Asymmetric Synthesis of Ester Functionalized Novel 1,4-Oxazepine Derivatives(01. Izmir Institute of Technology, 2021) Bozoğlu, Hülya; Çağır, Ali; Çağır, Ali; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 04. Faculty of ScienceThe MDM2/p53 is one of the most widely studied protein-protein interaction because of being a valuable target for the development of novel anticancer agents. MDM2 protein is the natural inhibitor of p53 protein which act as a tumor suppressor. When MDM2 is overexpressed, damaged DNA is allowed to replicate and therefore cancerous cells can be generated because p53 has lost of its activity. For this reason; maintaining the activity of wild-type p53 through inhibition of MDM2 can stop the proliferation of cancer cells. New drugs that inhibit this interaction are important for the treatment of cancer. The aim of the study is synthesize chiral 1,4-oxazepine-5-one derivatives. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material for the synthesis. The first step was a trityl protection of amine with trityl chloride. Trityl protected amino acid was reduced to N-Trt amino alcohol with LiAlH4 then oxidized to aldehyde by using Dess-Martin periodinane. The resulting aldehyde was reacted with 3-chlorophenylmagnesium bromide. Up to this part of the synthesis, reactions were performed successfully. Then trityl group was removed by TFA and amino alcohol was obtained. Then addition of several α,β-unsaturated carbonyls to the deprotected amino alcohol was studied by coupling reagents such as HATU. Afterwards we performed some intramolecular cyclization attempts but all cyclization attempts were failed.Master Thesis Synthesis of Novel Coumarin-1,2,3 Hybrids as Potential Anticancer Agents(01. Izmir Institute of Technology, 2021) Çağır, Ali; Çağır, Ali; 04.01. Department of Chemistry; 04. Faculty of Science; 01. Izmir Institute of TechnologyCoumarin and triazole derivatives have been extracted from plants, seeds and roots for ages in traditional methods. As the science advances, unknown profits of biologically active compounds have been investigating by researchers in modern laboratories. Extracts of natural sources containing coumarin and triazole derivatives were found to be potential natural medicines. The organic structures of these molecules bear extraordinary biological activities such as inflammatory activity, anti-HIV activity, treatment of cold and rheumatism and anticancer activity. In this study, attemps toward the synthesis of coumarin-triazole hybrids will be presented. At first attempt, starting from 2-amino-5-chlorophenol, coumarin-triazole hybrids were tried to be obtained through ynone intermediates, yet the experiments on acquiring corresponding ynone intermediates were failed. As second approach, 4-iodocoumarin and 4-bromocoumarin derivatives were tried to be synthesized from 4-hydroxycoumarin derivative that was acquired from acetyl salicylic acid, and the attempts were failed again. As an alternative, 4-tosylcoumarin derivative was used as pseudo halogenated coumarin derivative with triazole derivatives that were prepared starting from 4-chlorobenzyl azide. However, the failure was witnessed after all trials. In further trials, obtaining an internal alkyne as Sonogashira product from 4-tosylcoumarin derivative was the first step of another approach to produce desired hybrid structures. Unfortunately, in the second step a click chemistry between Sonogashira product and 4-cholorobenzyl azide was failed to form corresponding hybrid structures. Finally, possible Heck reaction was studied between coumarin derivative and 5-iodo-1,2-disubstituted-1,2,3-triazole derivative, that was also failed to obtain desired coumarin-triazole hybrid.Master Thesis Studies Toward the Asymmetric Synthesis of Novel Chiral 1,4-Oxazepan Derivatives(01. Izmir Institute of Technology, 2020) Vural, Ezgi; Çağır, Ali; Çağır, Ali; 01. Izmir Institute of Technology; 04.01. Department of Chemistry; 04. Faculty of SciencePharmacophore design to inhibit the interaction between p53 and MDM2 became a novel approach for cancer therapy. p53, known as the guardian of genome, controls the cell cycle arrest, apoptosis and DNA repair under stress. Nonetheless, when over-expressed, MDM2 causes proliferation in the cell and eventually tumorgenesis. The feedback mechanism between p53 and MDM2 arises from the interaction of p53 through the hydrophobic cleft which consists of Phe19, Trp23 and Leu26 aminoacids in the N-terminal of MDM2. In this study, it was aimed to synthesize a new, chiral 1,4-oxazepan-5-one derivatives by asymmetric synthesis. (R)-2-amino-2-(4-chlorophenyl)acetic acid was used as starting material. Amino group was protected by trityl group then the carboxylic acid part was reduced by LiAlH4 to produce N-trityl-protected amino alcohol. Dess Martin periodinane was used for the oxidation of the alcohol to the aldehyde, then 3-chlorophenylmagnesium bromide was added to the aldehyde by Grignard reaction. Deprotection of N-trityl was performed with TFA then, coupling reactions of produced aminoalcohol with different α,β-unsaturated carboxylic acids were performed by HATU and DIPEA. Despite all of the attempts, cyclization to seven membered 1,4-oxazepan-5-one ring was never achieved.