Synthesis of Terpenic Compounds with Advanced Functionalization via Biomimetic Methods Academic degree:
|
StatusThe thesis was presented on the 21 September, 2017Approved by NCAA on the 11 May, 2018 Abstract – 0.93 Mb / in romanian – 0.84 Mb / in englishThesisCZU
|
Keywords
Organic chemistry, organic synthesis, terpenoids, cyclization, rearrangement, functionalization, biomimetic, prenylationSummary
Thesis structure: introduction, 5 chapters, the first representing literature review and the next 4 chapters integrating the results of own investigations on the thesis subject, followed by general conclusions and recommendations, bibliography – 266 references, 219 pages of the main text, 121 Figures and 7 tables / Number of publications: research results have been published in 42 scientific works.
The aim and objectives of the thesis: Due to the fact that the majority of terpenic compounds which represent practical interest have complex carbon backbones and advanced functionalization with heteroatoms, the main aim of the current work was elaboration of synthesis methods for diverse classes of terpenic compounds by a flexible combination of major biomimetic processes, including oligomerization, cyclization, rearrangement and selective functionalization. The specific objectives of the work included the synthesis of terpenic compounds of different oligomeric series, having diverse functionalization pattern and their investigation in cyclization, rearrangement and heteroatom functionalization reactions.
Scientific novelty and originality of the research: A major influence of the functionalization pattern in the terpenoid skeletons on the cyclization/rearrangement reactions in vitro has been demonstrated in the present work. Addition of post-cyclization functionalization reactions to these synthetic transformations enlarge even more the arsenal of available synthetic tools for the generation of the entire structural diversity of terpenoids, preparing the ground for advanced studies on terpenic compounds utility in general. Conceptually novel scientific results for basic and applied science achieved: The current thesis has demonstrated the viability of the successive combination of different biomimetic processes for the synthesis of terpenic compounds with diverse structures. The relevant complexity of biogenetic paths which lead to the enormous structural diversity of terpenoids has prompted us to launch the hypothesis of the flexible combination of biosynthetic steps within biomimetic synthesis strategies. This approach has been defined as Random Biomimetic Synthesis. As a result of verification and valorization of thesis hypothesis, the synthesis of representatives from 15 different classes of terpenic compounds has been realized.
Theoretical and application value of the research: The main theoretical relevance of the work is based on the coining the Random Biomimetic Synthesis principle in planning the synthesis of complex natural product. The deep study of natural products with some specific structural features, basing on the same biogenetical root, has led to the identification of a super-family of cyclic terpenoids with terminal pendant prenyl groups. Implementation of the above mentioned scientific results has been expressed in the synthesis of 7 natural products or close precursors. In addition, initiation of research on ozonolytic cleavage of terpenoids in aqueous solvents has led to patenting of an efficient method for the production of sclareoloxide – an important compound with a broad use as component of aromatization compositions.
Summary
- 1.1 Synthesis of cyclic terpenoids with pendant terminal prenyl groups
- 1.2 Synthetic methods towards cheilanthanic sesterterpenoids
- 1.3 Methods for the synthesis of scalaranic sesterterpenoids
- 1.4 Conclusions to chapter 1
2. SYNTHEIS OF TERPENIC COMPOUNDS WITH MULTIPLE FUNCTIONALIZATION VIA OLIGOMERIZATION OR DIRECT FUNCTIONALIZATION
- 2.1 Direct functionalization of open chain terpenoids 73
- 2.2 Oligomerization approach in the synthesis of terpenes with multiple functionalization 80
- 2.3 Synthesis of terpenic compounds with multiple functionalization via oligomerization or direct functionalization. Experimental methods and procedures 86
- 2.4 Conclusions to chapter 2
3. SYNTHESIS OF CYCLIC TERPENIC COMPOUNDS BY SELECTIVE CYCLIZATION SEQUENCES
- 3.1 Synthesis of partially cyclized terpenic compounds by a selective biomimetic initiation of the cyclization cascade
- 3.2 Synthesis of partially cyclized terpenic compounds by a selective biomimetic suspension of cyclization cascade
- 3.3. Synthesis of cyclic terpenic compounds in non-conventional media. Superacidic cyclization in ionic liquids
- 3.4 Synthesis of cyclic terpenic compounds by selective cyclization sequences. Experimental methods and procedures
- 3.5 Conclusions to chapter 3
4. APPLICATION OF THE REARRANGEMENT BIOMIMETIC PROCESSES FOR THE SYNTHESIS OF SOME TERPENIC FAMILIES
- 4.1 Rearangement processes involving ring contractions. Synthesis of austrodoric acid and austrodoral
- 4.2 Rearangement processes involving functional group migrations
- 4.3 Application of the rearrangement biomimetic processes for the synthesis of some terpenic families. Experimental methods and procedures
- 4.4 Conclusions to chapter 4
5. APPLICATION OF THE OXIDATIVE - DEGRADATION BIOMIMETIC PROCESSES FOR THE SYNTHESIS OF SPECIFICALLY FUNCTIONALIZED TERPENES. REMOTE C-H FUNCTIONALIZATIONS
- 5.1 Synthesis of the perhydroindanic fragment of norrisolide
- 5.2 Biomimetic degradation processes based on ozonolysis
- 5.3 Terpene modification by functionalization of inactivated C-H bonds. Radical relay remote functionalization of scalaranic compounds
- 5.4. Application of the oxidative - degradation biomimetic processes for the synthesis of specifically functionalized terpenes. Remote C-H functionalizations. Experimental methods and procedures
- 5.5. Conclusions to chapter 5
OVERALL CONCLUSIONS AND RECOMMENDATIONS
Oficial Reviewers
- Aurelian Gulea
doctor habilitat, professor, Moldova State University - Iacob Guţu
doctor habilitat, professor, Moldova State University - MANGALAGIU Ionel
doctor, profesor, Universitatea „Alexandru Ioan Cuza” din Iași, România
Council's Members
- Fliur Macaev, president
doctor habilitat, professor, Institute of Chemistry of the ASM - Elena Gorincioi, secretary
doctor, associate professor (docent) - Aculina Aricu, member
doctor habilitat, associate professor (docent), Institute of Chemistry of the ASM - Valentin Bobeică, member
doctor habilitat, professor, Moldova State University - Grigore Junghietu , member
doctor habilitat, professor
Theses
