INVESTIGADORES
LEWKOWICZ Elizabeth Sandra
congresos y reuniones científicas
Título:
A chemoenzymatic process for the synthesis of acyclic nucleoside analogues involving the use of rabbit muscle aldolase (RAMA
Autor/es:
MARTÍN PALAZZOLO; ADOLFO IRIBARREN; ELIZABETH LEWKOWICZ
Lugar:
Tahormina
Reunión:
Simposio; X Simposio Internacional de Biocatalisis y Biotransformaciones (BIOTRANS 2011); 2011
Institución organizadora:
Sociedad Europea de Biocatalisis
Resumen:
For more than 40 years, nucleoside analogues have shown to be a valuable source of
antiviral and antitumor agents [1]. In particular, acyclic nucleosides received great
interest since the discovery of acyclovir in 1978-due to their extraordinary chemical
and biological stability.
Unlike natural nucleosides, the high flexibility ofthe C-C linkages enables the acyclic
analogues to adopt conformations that favor the formation of complexes with the
enzymes involved in their metabolism [2]. Often, the absolute configuration of the
stereogenic centers plays an important role in determining both their biological activity
and selectivity [3].
Aldolases are enzymes that catalyse stereospecific C-C bond condensation reactions. In
general, they possess strong dependence on the donor compound but show low
specificity towards the acceptor substrate [4]. Owing to these facts, they are a very
interesting tool for the synthesis of a variety of chiral compounds.
In this work, we describe a chemoenzymatic process for the preparation of thymidine
and adenosine acyclic analogues (Figure 1). This strategy involved the suitable N-alkylation of the nucleosidic bases to generate theacceptors for the subsequent aldol
condensation reaction biocatalysed by rabbit musclealdolase (RAMA). The expected
acyclic nucleoside analogues were obtained in moderate to high yields.