Author, Institution: Emilis Gudelis, Kaunas University of Technology
Science area, field of science: Natural Sciences, Chemistry, N003
Scientific Supervisor: Prof. Dr. Hab. Algirdas Šačkus (Kaunas University of Technology, Natural Sciences, Chemistry, N003)
Dissertation Defense Board of Chemistry Science Field:
Prof. Dr. Hab. Vytautas Mickevičius (Kaunas University of Technology, Natural Sciences, Chemistry, N003) – chairperson
Senior Researcher Dr. Marytė Daškevičienė (Kaunas University of Technology, Natural Sciences, Chemistry, N003)
Chief Researcher Dr. Linas Labanauskas (State Research Institute Center for Physical Sciences and Technology, Natural Sciences, Chemistry, N003)
Assoc. Prof. Dr. Jolanta Rousseau (Artois University, France, Technological Sciences, Chemical Engineering, T005)
Dr. Ingrida Tumosienė (Kaunas University of Technology, Natural Sciences, Chemistry, N003)
Dissertation defense meeting will be at Rectorate Hall of Kaunas University of Technology (K. Donelaičio 73-402, Kaunas)
The doctoral dissertation is available at the library of Kaunas University of Technology (Gedimino 50, Kaunas)
Annotation: The doctoral thesis presents a straightforward and efficient synthetic approach for the synthesis of novel heterocyclic amino acid derivatives containing the azetidine ring. The research primarily focuses on two main avenues: the development of novel chiral α- and achiral β-substituted [1-(tert-butoxycarbonyl)azetidin-3-yl]acetic acids and their derivatives. Such amino acids and their derivatives offer valuable properties as GABA isosteres, new conformationally restricted amino acids, and building blocks that can be used as potentially biologically active substances, as well as for the generation of DNA-encoded peptide libraries. To obtain β-substituted [1-(tert-butoxycarbonyl)azetidin-3-yl]acetic acid methyl esters, efficient and inexpensive 2-step synthesis was employed. In the first step, α,β-unsaturated ester tert-butyl 3-(2-methoxy-2-oxoethylidene)azetidine-1-carboxylate was obtained which was modified further by using commercially available aliphatic and aromatic N-heterocycles. One particular compound tert-butyl 3-(4-bromo-1H-pyrazol-1-yl)-3-(2-methoxy-2-oxoethyl)azetidine-1-carboxylate was subjected to further modification via Suzuki-Miyaura cross-coupling reaction by using aromatic and heteroaromatic boronic acids. To obtain enantiomerically pure α-substituted [1-(tert-butoxycarbonyl)azetidin-3-yl]acetic acids, a 6-step methodology was employed starting from α-alkylated phosphonates which were converted into racemic α-substituted [1-(tert-butoxycarbonyl)azetidin-3-yl]acetic acids via a 3-step process. Subsequently, racemic α-substituted [1-(tert-butoxycarbonyl)azetidin-3-yl]acetic acids were modified with Evan’s chiral auxiliaries, and the resulting diastereomers were separated by using column chromatography. Optically pure diastereomers were then subjected to oxidation to obtain enantiomerically pure α-substituted [1-(tert-butoxycarbonyl)azetidin-3-yl]acetic acids.
June 18 d. 09:00
Rectorate Hall at Kaunas University of Technology (K. Donelaičio 73-402, Kaunas)
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