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Synthesis of substituted oxindoles based on isatines


Author: Pogrebnoi Vsevolod
Degree:doctor of chemistry
Speciality: 02.00.03 - Organic chemistry
Year:2018
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 28 September, 2017
Approved by NCAA on the 11 May, 2018

Abstract

Adobe PDF document0.57 Mb / in romanian
Adobe PDF document0.54 Mb / in russian

Thesis

CZU 547.756:547.772.2:547.712.22:542 547.756:547.794.3:547.712.22:542 547.756:547.812.6:547.712.22:542

Adobe PDF document 2.06 Mb / in russian
147 pages


Keywords

Organic chemistry, organic synthesis, isatine, oxindoles, spiro-oxindoles, metalcomplex catalysis, organocatalysis.

Summary

Dissertation contents: Introduction, 3 chapters, general conclusions and recommendations, bibliography – 148 references, 129 pages of the main text, 100 pictures and 11 tables. Number of publications: Results are published in 21 scientific papers.

Key words: Organic chemistry, organic synthesis, isatine, oxindoles, spiro-oxindoles, metalcomplex catalysis, organocatalysis.

Field of study: Organic chemistry.

The aim of the scientific work: The thesis is dedicated to developing the novel paths of selective organic synthesis for obtaining the substituted oxindoles based on isatines, to study their structure and properties.

The research objectives: To develop simple and efficient synthetic schemes for obtaining the new substituted oxindoles based on isatines; to study regularity in dimerization pass of aryl2-oxoethilideneindoline-2-ones in synthesis of polycyclic oxindoles; to investigate the alternative pathways in synthesis of polycyclic oxindoles involving acetoacetic ester; to estimate the “structure-activity” relationship in a series of synthesized compounds.

Solved important scientific challenge: The presented in the thesis results contribute to the solution of the problem of selective organic synthesis of some novel substituted oxindoles with original structures and investigation of “structure-activity” relationship.

Scientific novelty and originality of present research: The original paths have been developed in selective organic synthesis towards the previously unknown substituted oxindoles and spirooxindoles. For the first time the synthesis of ethyl[2-methyl-4-(2-oxoindolin-3-il)-5-phenyl-1Н3-pirrol]carboxylate has been proposed, by using the iron-containing carboxy-functionalized imidazolium salts as catalyst, and the prospects of their recycling have been illustrated. The conversion to analogues of the natural alkaloids – Convolutamydine A and Welwitindolinones has been realized for the first time in last case the process being diastereoselective. “One-pot” synthesis of spirolactoneoxindoles has been developed and the dependence between length of alkyl radical in the initial 5-bromoisatine and process course has been found.

Theoretical and application value of the research: The results of this study contribute to the development of organic chemistry. Isatines were subjected to synthetic conversions into various functionalized oxindoles and spiro-oxindoles. The developed methods have formed a basis in approaching the synthesis of substituted oxindoles, including spiro-oxindoles with secohydrocarbon scaffold of Welwitindolinone alkaloids. According to the obtained data by the method of virtual screening the synthesized substituted oxindoles may stabilize the human p53 oncosupressor protein family and inhibit the tumor cell growth. The N-glucosylated Convolutamydine A has been synthesized for the first time. The proposed method can be used for synthesis of the similar compounds containing a monosaccharide fragment, endowed with higher bioavailability.

Implementation of the scientific results: Several results of the research presented in this thesis were integrated into research-and-development activity of the Institute of Chemistry of the ASM, as well as the St. Petersburg State Technological Institute, Russia.