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.
Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:2558 |
Date | 04 June 2010 |
Creators | Ventrici, Caterina <1982> |
Contributors | Giacomini, Daria |
Publisher | Alma Mater Studiorum - Università di Bologna |
Source Sets | Università di Bologna |
Language | Italian |
Detected Language | English |
Type | Doctoral Thesis, PeerReviewed |
Format | application/pdf |
Rights | info:eu-repo/semantics/openAccess |
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