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J. M. SÁNCHEZ-MONTERO Y J. V. SINISTERRA GAGO ANAL. REAL ACAD. NAC. FARM.

ción o de modificación química, control de la actividad de agua etc. Se describen
algunos procesos de interés desarrollados en el grupo como la resolución de racé-
micos y su aplicación a la obtención de ácidos S-2-arilpropiónicos o de ß-bloquean-
tes adrenérgicos; la reducción estereoselectiva de cetonas proquirales, la síntesis
en un paso de nucleósidos con actividad farmacológica etc. En todos los casos se
comentan las ventajas de las nuevas metodologías de síntesis en sintonía con la
nueva normativa de obligado cumplimiento de la UE sobre eliminación de disol-
ventes contaminantes (CH2Cl2, TCE), inflamables (hexano, isooctano), compuestos
orgánicos volátiles (COV) etc, y de reactivos contaminantes v.g.: catalizadores
órgano metálicos.

Palabras clave: Biocatálisis, Biotransformaciones, fármacos racémicos, quími-
ca verde.

ABSTRACT

Enzymes and microorganisms as catalysts in the synthesis of products
of pharmaceutical interest.

Pharmaceutical industries are nowadays facing the challenge of lowering the
ratio (kg of residues/kg of product) to levels below 200, as required by the Euro-
pean legislation. This fact is demanding the implementation of more selective and
efficient synthetic procedures, so that new and better catalysts are needed. For this
purpose, Applied Biocatalysis, and more specifically Biotransformation (the use of
the former in Organic Synthesis), are becoming more prominent in the design of
new strategies for drugs synthesis. In this review, some of the methodologies
applied inside the Biotransformations Group of the Complutense University are
presented; thus, the employ of different methodologies (such as immobilization
and/or modification of biocatalysts, or the control of water activity of the reaction
media) for improving the biocatalyst performance are described. The biocatalyzed
resolution of racemates for obtaining enantiopure S-2-aryl propionic acids (pro-
fens) or cardiotonic ß-blockers, the estereoselective carbonyl reduction of prochiral
ketones, or the one-step semi-synthesis of therapeutically significant nucleosides
will be discussed. In all cases, a special emphasis is set on the environmental
advantages of the biocatalyzed processes, as demanded by EU legislation on subs-
titution of contaminant solvents (CH2Cl2, TCE) or reagents (organo metallic ca-
talysts), as well as highly flammable compounds (n-hexane, isooctane), or promo-
ting VOCs release.

Key words: Biocatalysis, Biotransformations, racemics drugs, green chemistry.

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