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Structure and reactivity of some ß-lactams in alkaline hydrolysis


Žiher, Dinko; Gabelica, Vesna; Mihalić, Zlatko
Structure and reactivity of some ß-lactams in alkaline hydrolysis // 8th European Symposium on Organic Reactivity (ESOR VIII)
Cavtat, Croatia, 2001. (poster, nije recenziran, sažetak, znanstveni)


Naslov
Structure and reactivity of some ß-lactams in alkaline hydrolysis

Autori
Žiher, Dinko ; Gabelica, Vesna ; Mihalić, Zlatko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
8th European Symposium on Organic Reactivity (ESOR VIII)

Mjesto i datum
Cavtat, Croatia, 01-06.09.2001

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
SS-lactam; alkaline hydrolysis; SAR

Sažetak
Design and synthesis of ß-lactams with antibiotic activity continues to be one of the major challenges in the pharmaceutical industry. Main step in the mechanism of interaction between ß-lactam and different enzymes is a nucleophilic attack of serine on the carbonyl group of ß-lactam. This reaction can be mimicked by a nucleophilic attack of a hydroxide ion on the ß-lactams ring. Alkaline hydrolysis of a series of C6 unsubstituted, α -C6-brominated and C6-dibrominated ß-lactams has been investigated. Kinetic study was performed in aqueous sodium hydroxide (0.5-2M) at 35°C. Rate constants were determined spectrophotometrically by monitoring the disappearance of the substrate. The geometries were optimised at the semiempirical and DFT level. A steric effect of bromine substituent is apparent and a nucleophilic attack of the hydroxide ion on the ß-lactam carbonyl group is disrupted. Substitutions on the C6 position and oxidation state of the sulphur atom have a significant influence on the conformation of ß-lactam molecules and hydrolysis of ß-lactam ring. The importance of steric hindrance and the changes in pyramidality of nitrogen, as well as formation of intramolecular hydrogen bonds among amide groups will be discussed in this paper.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Ustanove
Pliva-Istraživački institut,
Prirodoslovno-matematički fakultet, Zagreb