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Synthesis and exploration of nitrogen-containing 3,7,7-trimethylbicyclo[4.1.0]heptane derivatives based on (+)-3-care


Author: Curlat Serghei
Degree:doctor of chemistry
Speciality: 02.00.03 - Organic chemistry
Year:2021
Scientific adviser: Fliur Macaev
doctor habilitat, associate professor (docent), Institute of Chemistry of the ASM
Institution: Institute of Chemistry of the ASM

Status

The thesis was presented on the 18 February, 2021 at the meeting of the Scientific Council and now it is under consideration of the National Council.

Abstract

Adobe PDF document1.03 Mb / in romanian
Adobe PDF document1.08 Mb / in english

Thesis

CZU 547.5 547.7/.8 547.91

Adobe PDF document 2.89 Mb / in russian
165 pages


Keywords

+)-3-carene, epoxidation, quaternization, chiral ionic liquids, cycloaddition, 1,2,3-triazoles, bis-amines, 2,6-dimethylpyridine-3,5-dicarboxylates

Summary

Dissertation content: introduction, list of abbreviations, review of literature on selected topics, discussion of the results of own research, general conclusions, list of references, including 138 titles, 122 pages of main text, 73 figures, 6 tables, the results are published in 25 scientific works.

The goal of the scientific work: This work is dedicated to the development and implementation of synthetic strategy and the determination of structure - properties dependence for 55 new nitrogen-containing 3,7,7-trimethylbicyclo[4.1.0]heptane derivatives based on (+)-3-carene.

The research objectives: Development of practical (+)-3-carene epoxidation pathway, establishing of the optimal conditions for regioselective opening of trans-epoxide by heterocyclic amines, identifying features of the quaternization reaction of the compounds obtained, studying the specificity of the reaction of cycloaddition of isomeric azidocaranols with terminal alkynes, extending the range of application of the aminoalkylation reaction to the aziridine of carane series.

The novelty and scientific originality of the work: the implementing of an environmental friendly method for (+)-3-carene epoxidation. A number of carane-functionalized heterocyclic amines were obtained, their structure and properties were studied. The introduction of the azido group into the carane skeleton made it possible to study the applicability of the click-reaction of the azide-alkine cycloaddition in this case, as well as to obtain a series of aziridines of carane series.

Solved important scientific problem consists in: determination of the optimal synthesis conditions and establish of the relationship between the structure, cytotoxicity, anti-HIV and antioxidant activity of previously unknown nitrogen-containing derivatives of 3,7,7-trimethylbicyclo [4.1.0] heptanes with high potential of applicability in biopharmaceutics.

Theoretical significance of the dissertation: The specificity of the reactions of trans-epoxide with 1H-1,2,4-triazole, 1H-benzotriazole, 1H-imidazole and 1H-benzimidazole, including under microwave irradiation conditions, have been established. It was established that acetoacetates of caranes series, unlike acetoacetic ester react with formalin and ammonium acetate to form 2,6-dimethylpyridine-3,5-dicarboxylic esters. The synthesis of aminoalkylated aziridines of carane series have been carried out by condensation of caranic aziridine with formaldehyde and secondary amines.

Practical significance of the dissertation: A new eco-friendly epoxidation process for (+)-3-carene using H2O2/α-Al2O3 has been proposed. The conversion of the obtained epoxide allowed to obtain compounds, in particular derivatives of 1H-benzimidazole and 1Hbenzotriazole, which capacity of inhibiting HIV transcriptase is of practical interest.

Implementation of the scientific results: The patented epoxidation method using the nanoscale α-Al2O3/H2O2 system has found application in the research activities of the laboratory. Data on antioxidant, anti-HIV activities and cytotoxicity revealed promising substances for further indepth