Ventrici, Caterina
(2010)
Progettazione e sintesi di nuovi derivati azetidinonici biologicamente attivi, [Dissertation thesis], Alma Mater Studiorum Università di Bologna.
Dottorato di ricerca in
Scienze chimiche, 22 Ciclo. DOI 10.6092/unibo/amsdottorato/2558.
Documenti full-text disponibili:
Abstract
In this PhD-thesis new synthetic approaches towards new azetidinone derivatives are described. In particular, 4-alkyliden-β-lactams were used as starting materials for the preparation of new biologically active compounds.
The carbapenem Thienamycin has got a broad spectrum of activity as antibiotic. It has got 3 stereocenters and apart of one epimer, all isomers have been synthesized. Using the 4-alkyliden-β-lactam benzilyc ester as precursor, we developed a synthesis for this missing epimer, which is described in chapter II. Biological tests in order to establish its biological activity are under way.
The Hunsdiecker-Borodine reaction was extensively studied for the preparation of the mono halogenated and – surprisingly – the dihalogenated derivative from the 4-alkyliden-azetidinone carboxylic acid. The herein described synthetic procedures allowed the preparation of chloro-, bromo- and iodo derivatives in good to excellent yield. Furthermore, the reaction mechanism was investigated by NMR-experiments and is described in detail in chapter III.
In chapter IV, synthetic approaches towards new β-lactam derivatives for inhibition of the histone deacetylase enzymes (HDACs) are reported. In collaboration with the company Sigma-Tau (Rome), 14 new β-lactams were synthesized. The new β-lactams were evaluated for the activity showing a promising activityparticulary, 10 of the β-lactams synthesized were evaluated for the in vitro inhibitory activity against the 11 human HDACs isoforms and they showed a selective inhibition of HDAC6 or HDAC8 in micromolar range.
Finally, preliminary studies were conducted for the employment of 4-alkyliden-β-lactams as precursors for the synthesis of chiral β-amino acids by an opening of the β-lactam ring. In chapter V is described the ring opening reaction catalyzed by the enzyme lipase Cal-B. Preliminary results have shown that the enzyme not only catalyzes the ring opening of the β-lactam precursor, moreover, it leads to the formation of a cyclic dimer by the reaction of two molecules of β-amino acid obtained.
Abstract
In this PhD-thesis new synthetic approaches towards new azetidinone derivatives are described. In particular, 4-alkyliden-β-lactams were used as starting materials for the preparation of new biologically active compounds.
The carbapenem Thienamycin has got a broad spectrum of activity as antibiotic. It has got 3 stereocenters and apart of one epimer, all isomers have been synthesized. Using the 4-alkyliden-β-lactam benzilyc ester as precursor, we developed a synthesis for this missing epimer, which is described in chapter II. Biological tests in order to establish its biological activity are under way.
The Hunsdiecker-Borodine reaction was extensively studied for the preparation of the mono halogenated and – surprisingly – the dihalogenated derivative from the 4-alkyliden-azetidinone carboxylic acid. The herein described synthetic procedures allowed the preparation of chloro-, bromo- and iodo derivatives in good to excellent yield. Furthermore, the reaction mechanism was investigated by NMR-experiments and is described in detail in chapter III.
In chapter IV, synthetic approaches towards new β-lactam derivatives for inhibition of the histone deacetylase enzymes (HDACs) are reported. In collaboration with the company Sigma-Tau (Rome), 14 new β-lactams were synthesized. The new β-lactams were evaluated for the activity showing a promising activityparticulary, 10 of the β-lactams synthesized were evaluated for the in vitro inhibitory activity against the 11 human HDACs isoforms and they showed a selective inhibition of HDAC6 or HDAC8 in micromolar range.
Finally, preliminary studies were conducted for the employment of 4-alkyliden-β-lactams as precursors for the synthesis of chiral β-amino acids by an opening of the β-lactam ring. In chapter V is described the ring opening reaction catalyzed by the enzyme lipase Cal-B. Preliminary results have shown that the enzyme not only catalyzes the ring opening of the β-lactam precursor, moreover, it leads to the formation of a cyclic dimer by the reaction of two molecules of β-amino acid obtained.
Tipologia del documento
Tesi di dottorato
Autore
Ventrici, Caterina
Supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze chimiche
Ciclo
22
Coordinatore
Settore disciplinare
Settore concorsuale
URN:NBN
DOI
10.6092/unibo/amsdottorato/2558
Data di discussione
4 Giugno 2010
URI
Altri metadati
Tipologia del documento
Tesi di dottorato
Autore
Ventrici, Caterina
Supervisore
Dottorato di ricerca
Scuola di dottorato
Scienze chimiche
Ciclo
22
Coordinatore
Settore disciplinare
Settore concorsuale
URN:NBN
DOI
10.6092/unibo/amsdottorato/2558
Data di discussione
4 Giugno 2010
URI
Statistica sui download
Gestione del documento: