Enzymatic synthesis of citalopram derivative comprises diol treatment with acylating agent in presence of Candida antarctica lipase

Synthesis of optically enriched enantiomers of citalopram derivative comprises treatment of 4-[4-dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile (I) with acylating agent in the presence of lipase B of Candida antarctica, hydrolyzing the resulting ester and cyclizing. An independent claim is also included for the following new compounds: (1) optically enriched enantiomers of 4-[4-dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile (I); and (2) optically enriched esters of (I) where the hydroxymethyl group is acylated by alkanoyl or aroyl groups. Synthesis of optically enriched enantiomers of citalopram derivative comprises treatment of 4-[4-dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile (I) with acylating agent in the presence of lipase B of Candida antarctica, hydrolyzing the resulting ester and cyclizing. An independent claim is also included for the following new compounds: (1) optically enriched enantiomers of 4-[4-dimethylamino-1-(4-fluoro-phenyl)-1-hydroxy-butyl]-3-hydroxymethyl-benzonitrile (I) and (2) optically enriched esters of (I) where the hydroxymethyl group is acylated by alkanoyl or aroyl groups. (Machine-translation by Google Translate, not legally binding) Síntesis quimioenzimática de (+)-citalopram y (-)-citalopram. Se describe la síntesis de (+)-citalopram y (-)-citalopram mediante procesos quimioenzimáticos. El primero consiste en el tratamiento del diol(+-)-9 con un agente acilante en presencia de lipasa B de Candida antarctica. Así se consigue el diol (-)-9 de forma enantiopura, que se transforma en (+)-citalopram por ciclación. De igual forma, se puede llegar a (-)-citalopram mediante hidrólisis del éster (+)-10 y posterior ciclación del diol (+)-9. En otra variante de la invención, el paso enzimático consiste en la hidrólisis en presencia de lipasa B de Candida antárctica del éster (+-)-10 obtenido por acilación del diol (ñ)-9. Así se consigue el éster (-)-10 de forma enantiopura, que se transforma en (+)- citalopram mediante hidrólisis y posterior ciclación. De igual forma, se puede obtener (-)-citalopram a partir del diol (+)-9 por ciclación.