StatusThe thesis was presented on the 16 June, 2020
Approved by NCAA on the 30 October, 2020
Abstract– 1.71 Mb / in romanian
– 1.68 Mb / in english
ThesisCZU 547.596/.597:577.1 (043.2)
4.52 Mb /
Gîrbu Vladilena, "Synthesis of polyfunctionalized terpenic derivatives via radical and cationic reactions", PhD thesis in chemical science, Chișinău 2019. Structure of the thesis: Introduction, 4 chapters, general conclusions and recommendations, bibliography of 203 references, 111 basic text pages, 65 figures, 6 tables, 1 annex. The results of the research have published in 20 scientific papers. Key-words: terpenoids, radical chemistry, carboazidation, carbohydrogenation, hydroazidation, skeletal rearrangements, biologically active compounds. The aim of the thesis: is functionalization of terpenoids with nitrogen, oxygen and halogen heteroatoms through radical reactions thus obtaining compounds with high potential biological activity; modification of readily available terpenoids via skeletal rearrangements and generation of compounds with rearranged skeletons. Research objectives: the use of hydroazidation, carboazidation and carbohydrogenation radical reactions for the functionalization of natural and synthetic diterpenoids; modification of the carbonic skeleton in isocopalic and homodrimanic derivatives through cationic migrations to obtain the terpenic derivatives, the analogues of which are found in nature in a small amount; characterization of the compounds using modern methods of analysis. Scientific novelty and the originality: For the first time, the usefulness of radical addition with atom transfer has been demonstrated for the functionalization of diterpenic compounds, such as ent-kaurane, labdane and isocopal derivatives. Ninety new compounds have been synthesized, some showing pronounced biological activity. For the first time, due to cationic transpositions, compounds with halimane, ent-verrucosin and hyrtiosane skeleton have been synthesized. The results which can contribute to the solution of an important scientific problem in the thesis consist in the simultaneous introduction of functional groups via radical reactions and obtaining labdanic, ent-kauranic and isocopalic compounds functionalized with nitrogen, oxygen or halogen heteroatoms, some demonstrating biological activity; a series of sesquiterpenoids with halimane, hyrtiosane and ent-verrucosin skeleton, compounds with theoretical and applicative value have been obtained. The theoretical value: consists in the successful application of radical transformations for broadening the structural diversity of terpenic compounds with complex structure, demonstrating the influence of stereoelectronic effects on the selectivity of the processes approached and developing efficient ways of functionalization of the selected substrates based on radical and cationic reactions. The applicative value of the research is the viability of radical chemistry on complex terpenic substrates; demonstration of the click reaction on diterpenic substrates and their use in biological activity studies. The implementation of scientific results: a number of compounds synthesized throughout the research demonstrated selective cytotoxic activity. Based on these results, four patent applications have been filed.