Recent advances in the industrial enzymatic synthesis of semi-synthetic B-lactam antibiotics.

ANTIINFECCIOSOS

SINTESIS

ENZIMAS

BIBLIOGRAFIA NACIONAL QUIMICA

2005

The production, under environmentally benign conditions, of efficient and more cost-effective anti-infective agents (available to the whole mankind) is one of most ambitious dreams of the industrial medicinal chemistry. Semi-synthetic b-lactam antibiotics are very effective anti-infective agents. They are very stable and can be used via oral delivery. They exhibit a very wide spectrum of anti-bacterial activity and minimal side effects after being massively used for a very long time. In this way, we can assume that semi-synthetic b-lactam antibiotics are going to be one of the key anti-infective agents in the next years. The condensation of natural or modified antibiotic nuclei with different acyl donor chains is one of the key steps for the industrial synthesis of these anti-infective agents. Up to now, these condensations are mainly carried out through classical chemical methods and this implies a number of economical, ecological and technological drawbacks (high energy requirements, many protection and deprotection steps, utilization of toxic methylene chloride as solvent, etc). Enzyme biocatalysts may be very useful to catalyse these selective condensations under very mild experimental and environmental conditions. In fact, the possibility of using enzymes to carry out such biotransformations, at laboratory scale, has been discussed and demonstrated a long time ago. However, industrial synthesis of b-lactamic antibiotics is still carried out via unfavorable chemical routes. In fact, enzymes have not been produced in the nature to act in industrial reactors; so they are usually very unstable, inhibited by substrates and products and they may not have ideal catalytic properties for industrial uses (high reaction rates, required selectivity, ability to reach quantitative synthetic yields, stable enough to run a number of reaction cycles, etc). These limitations of enzyme biocatalysis become even more significant mainly when the enzyme is going to be used with non-natural substrates, catalysing non-natural processes and working under non-conventional conditions. However, in the last ten years, a great number of papers have reported substantial improvement of these enzymatic synthetic approaches (new enzymes, better enzyme derivatives, improved reaction designs and so on) and it seems that a massive industrial implementation of enzymes in antibiotic synthesis is approaching. In this review, we would like to make a critical discussion of these very interesting advances in the application of enzyme biocatalysts for the industrial synthesis of semi-synthetic antibiotics.

Medicinal Chemistry Reviews v. 2, no. 3, 2005. -- p. 207-218

Bentham Science

2005

Información sobre Derechos de Autor

(Por favor lea este aviso antes de abrir los documentos u objetos)

La legislación uruguaya protege el derecho de autor sobre toda creación literaria, científica o artística, tanto en lo que tiene que ver con sus derechos morales, como en lo referente a los derechos patrimoniales con sujeción a lo establecido por el derecho común y las siguientes leyes

(LEY 9.739 DE 17 DE DICIEMBRE DE 1937 SOBRE PROPIEDAD LITERARIA Y ARTISTICA CON LAS MODIFICACIONES INTRODUCIDAS POR LA LEY DE DERECHO DE AUTOR Y DERECHOS CONEXOS No. 17.616 DE 10 DE ENERO DE 2003, LEY 17.805 DE 26 DE AGOSTO DE 2004, LEY 18.046 DE 24 DE OCTUBRE DE 2006 LEY 18.046 DE 24 DE OCTUBRE DE 2006)

ADVERTENCIA - La consulta de este documento queda condicionada a la aceptación de las siguientes condiciones de uso: Este documento es únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con fines de lucro. Esta reserva de derechos afecta tanto los datos del documento como a sus contenidos. En la utilización o cita de partes debe indicarse el nombre de la persona autora

PDF

Inglés

Artículo

DOI: 1567-2034/05

PDF