𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Theoretical Calculations of β-Lactam Antibiotics. Part VI. AM1 calculations of alkaline hydrolysis of clavulanic acid

✍ Scribed by Juan Frau; Josefa Donoso; Francisco Muñoz; Francisco García Blanco

Publisher
John Wiley and Sons
Year
1994
Tongue
German
Weight
989 KB
Volume
77
Category
Article
ISSN
0018-019X

No coin nor oath required. For personal study only.

✦ Synopsis

The gas-phase basic hydrolysis of clavulanic acid (a) was studied by using the AM1 semi-empirical method. The results obtained show that the hydroxyethylidene side chain at C(2) is pivotal to the stability of the different reaction products involved. The products with an open oxazolidine ring are more stable than those with a closed ring fused to theg -1actam ring. This behaviour differs from that of penicillins and cephalosporins where the most stable degradation products are those with an intact thiazolidine or dihydrothiazine ring, respectively, fused to the -lactam ring. The different chemical reacivity of clavulanic acid relative to penicillins and cephalosporins could explain the disparate behaviour of the latter two types of compound towardsa -1actamases. Once the acyl-enzyme intermediate of clavulanic acid has been formed, it can evolve with cleavage of the oxazolidine ring to form a difficult to deacylate compound.

📜 SIMILAR VOLUMES

Theoretical calculations of β-lactam ant
Theoretical calculations of β-lactam antibiotics. III. AM1, MNDO, and MINDO/3 calculations of hydrolysis of β-lactam compound (azetidin-2-one ring)
✍ J. Frau; J. Donoso; F. Muñoz; F. García Blanco 📂 Article 📅 1992 🏛 John Wiley and Sons 🌐 English ⚖ 905 KB

Semiempirical AM1, MINDO/3, and MNDO methods have been used in the study of the alkaline hydrolysis of P-lactam antibiotics through a base-catalyzed, acyl-cleavage, bimolecular mechanism. In this work, the hydroxyl ion has been chosen as nucleophilic agent and the azetidin-2-one ring like a model of

Theoretical calculations of β-lactam ant
Theoretical calculations of β-lactam antibiotics. V. AM1 calculations of hydrolysis of cephalothin in gaseous phase and influence of the solvent
✍ J. Frau; J. Donoso; F. Muñoz; F. García Blanco 📂 Article 📅 1993 🏛 John Wiley and Sons 🌐 English ⚖ 697 KB

A comprehensive study on the gas-phase alkaline hydrolysis of cephalosporins by using the semiempirical AM1 method was carried out. Cephalothin was the model compound used on account of the presence of a good leaving group at C(3'). According to the results obtained, the hydrolysis process takes pla

Theoretical Calculations of β-Lactam Ant
Theoretical Calculations of β-Lactam Antibiotics. Part VII. Influence of the solvent on the basic hydrolysis of the β-lactam ring
✍ Juan Frau; Josefa Donoso; Francisco Muñoz; Francisco Gracia-Blanco 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 German ⚖ 571 KB

We used semi-empirical and ab initio calculations to investigate the nucleophilic attack of the OHion on the 8-lactam carbonyl group. Both allowed us to detect reaction intermediates pertaining to proton-transfer reactions rather than the studied reaction. We also used the PM3 semi-empirical method