Announcement of the thesis defense of the Doctor of Philosophy (PhD) Ubaydullaev Azizjon Ubaydullaevich

announcement of the thesis defense of the Doctor of Philosophy (PhD) Ubaydullaev Azizjon Ubaydullaevich

I. General information

The topic of the dissertation, the cipher of the specialty (the name of the branch of science in which the academic degree is awarded): “Synthesis, structure and properties of derivatives of quinoline alkaloid haplophilidine”, 02.00.03 – Organic chemistry (chemical sciences).

The registration number of the thesis topic: В2024.3.PhD/K826.

Scientific supervisor: Doctor of Chemical Sciences, senior scientific researcher Jurakulov Sherzod Niyatkobulovich.

The name of the institution where the dissertation was performed: S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan.

The name of the institution where the Scientific council works, the number of the scientific council: S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan, DSс.02/30.01.2020. К/Т. 104.01.

Official opponents: Doctor of Chemical Sciences, Professor Xoliqov Tursunali Suyunovich, doctor of chemical sciences, senior scientific researcher Khodjaniyazov Khamid Utkirovich.

Leading organization: Samarkand State University.

II. The purpose of the study. Comparison of electrophilic substitution, electrophilic addition, and nucleophilic addition reactions in bromination and nitration reactions of the quinoline alkaloids haplophyllidine and acetylhaplophyllidine under various conditions, as well as the study of their reactions with acids, and determination of the structure and physicochemical properties of the resulting compounds.

III. Scientific novelty of the research:

It has been proven for the first time that in the bromination reactions of haplophyllidine with molecular bromine and N-bromosuccinimide (NBS), a carbocation is formed as a result of the electrophilic addition of bromine to the double bond of the prenyl group in the haplophyllidine molecule, and intramolecular cyclization occurs as a result of the competitive nucleophilic reaction of the functional groups (hydroxyl, methoxyl) in the molecule, resulting in the formation of new compounds with a bromine-bound spiro, five- and six-membered ring structure. The reaction mechanism for the bromination of haplophyllidine with molecular bromine and NBS is proposed;

for the first time, it has been proven that in the bromination reactions of acetylhaplophyllidine with molecular bromine and NBS, electrophilic substitution occurs in the prenyl group and furan ring, resulting in the dimethylation of the methoxyl group in the quinoline ring, which leaves the methoxyl group in the form of methyl bromide, followed by electrophilic addition of bromine to the acetylhaplophyllidine molecule along with mono- and di-bromoquinolin-4-ones, and intramolecular cyclization occurs as a result of the competitive nucleophilic action of the oxygen or nitrogen atoms of the methoxyl group at the C-8 position, resulting in the formation of bromine-bound spiro, six-membered quinolin-4-ones;

for the first time, the elimination of methanol from the methoxyl group under the action of nitrating mixtures of haplophyllidine and anhydroperforin at a temperature of 65-70℃ results in the formation of a double bond in the C7=C8 position, and then, as a result of oxidation of the A-ring, it turns into an aromatic ring. At the same time, electrophilic substitution of the furan ring with a nitro group results in the formation of 2-nitrofuranoquinoline, and the electrophilic addition of the nitro group and the nucleophilic action of a water molecule result in the formation of 2-nitro-3-hydroxy-2,3-dihydrofuranoquinoline. It was also found that a nitroester of haplophyllidine is formed in a mixture of acetic anhydride and nitric acid; the mechanism of the nitration reaction of anhydroperforin is proposed;

It was first demonstrated that, under the influence of nitrating mixtures of acetylhaplophyllidine at a temperature of 65-70℃, intramolecular cyclization occurs as a result of the competitive nucleophilic action of the oxygen of the complex ether group in the acetylhaplophyllidine molecule, or the oxygen of the methoxyl group at the C-8 position, and spiro, six-membered compounds are formed. At the same time, it was proven that the A ring of the compound is oxidized to an aromatic ring and the furan ring is nitrated to form a 2-nitrofuranoquinoline derivative;

the structure of the synthesized substances has been fully proven using mass spectrometric, NMR, IR spectroscopic and RTD methods.

IV. Implementation of the research results.

Based on the scientific results obtained on the synthesis and chemical modification of new compounds based on the furanoquinoline alkaloids haplophylidine, anhydroperforin and acetylhaplophylidine: the crystal structures of seven compounds were determined and included in the international Central Cambridge Crystallographic Database (The Cambridge Structural Database, https://www.ccdc.cam, CCDC: 2219735 (1), 2169949 (3), 2169950 (4), 2169951 (5), 2294287 (19), 2294288 (20), 2294289 (22)). As a result, it was possible to synthesize similar compounds and study their spatial structures by comparison;

The results obtained were used in the fundamental project “Search for effective drugs with high biological activity based on alkaloids of plants of the flora of Uzbekistan” (2021-2024) carried out at the Laboratory of Alkaloid Chemistry of the Institute of Chemistry of Plant Substances (Reference of the Academy of Sciences of the Republic of Uzbekistan dated October 7, 2024 No. 4/1255-2215). As a result, new biologically active derivatives of quinoline alkaloids were obtained, and the synthesis methods were recommended for application to other N-containing compounds.

Chairman of scientific council Sagdullaev Sh. Sh.

Scientific secretary of the scientific council Khidirova N.K.

Scientific supervisor Jurakulov Sh. N.

The applicant: Ubaydullaev A.U.

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