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Synthesis of some functionalized bicyclic nitrogen containing di- and sesquiterpenoids and a study of their biological activity


Author: Secară Elena
Degree:doctor of chemistry
Speciality: 02.00.10 - Bioorganic chemistry; chemistry of natural and physiological active compounds
Year:2019
Scientific adviser: Aculina Aricu
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 4 April, 2019
Approved by NCAA on the 9 July, 2019

Abstract

Adobe PDF document – 0.94 Mb / in romanian

Thesis

CZU 577.1:[547.597:546.17] (043.2)

Adobe PDF document 4.11 Mb / in romanian
156 pages

Keywords

synthesis, bicyclic diterpenoids, bicyclic sesquiterpenoids, stereoselectivity, biological activity, amides, amines, guanidines, hidrazides, dihidrazides, azine, lactams

Summary

Dissertation contents: introduction, tree chapters, general conclusions and recommendations, bibliography with 172 references, 8 annexes, 129 pages of main text, 60 figures, and 24 tables. Number of publications: results are published in 9 articles, 15 abstracts, 4 national invention.

Field of the research: 143.04. - Bioorganic chemistry, chemistry of natural and physiologically active compounds.

The aim: the thesis is devoted to the realization of the directed synthesis of some bicyclic nitrogen-containing diterpenoids and sesquiterpenoids based on available natural diterpenoid -sclareol, to the elucidation of the possible reactions mechanisms and to the selection of the optimal conditions for the preparation of the above-named compounds possessing high bioactivity potential. Objectives: synthesis of drimane and homodrimane sesquiterpenoids containing diazines, 1,2,4-triazole and carbazole cycles; the investigation of the Beckmann rearrangement of the some ketoximes; synthesis of dihomodrimane and 14,15-dinorlabdane terpenoids with the amino- group and the guanidine, azine, hydrazide and dihydrazide fragments; the determination of the structure and stereochemistry of the synthesized new compounds, as well as the testing of their biological activity.

Scientific novelty and originality. The conducted research led to the development of the original methods of the obtaining of new functionalized bicyclic diterpenoids and sesquiterpenoids containing nitrogen, for the creation of natural chiral molecules of interest for the pharmaceutical industry. The functionalization of bicyclic di- and sesquiterpenoids was carried out both in the side chain and in the B-cycle, producing lactams and the derivatives with an amino group, as well as containing the azine, hydrazide, dihydrazide, guanidine and heterocyclic fragments.

Solved scientific problem. The stereoselective methods of synthesis of some nitrogencontaining compounds, starting from the natural diterpenoid sclareol, were developed. New nitrogen-functionalized bicyclic di- and sesquiterpenoids are the important chiral synthons for the controlled synthesis of new compounds with the potential biological activity.

Theoretical value. The structural and steric regularities in the reactions of obtaining the new drimane, homodrimane and diterpene nitrogen-containing compounds that have the high potential of biological activity, of both scientific and practical importance, were studied.

The practical significance of this work. A series of various nitrogen-containing bicyclic di- and sesquiterpenoids was synthesized. The bioactivity of the obtained 16 substances was investigated. Five compounds showed the pronounced antifungal and antibacterial activity, two new amides showed the pronounced antioxidant activity, and two derivatives with guanidine fragment showed high antitumor activity.

The implementation of scientific results. Evaluation of the biological activity of the newly synthesized compounds made it possible to identify substances with a very high degree of activity, which may be the subject of the further deeper studies with a view to their practical implementation.