An efficient biocatalytic procedure to obtain chiral N,O-nucleoside derivatives consisting of a lipase-catalysed resolution of the corresponding racemates in organic solvent has been developed. Enantioselective esterification of thymine and cytosine derivatives, (±)-9a and (±)-9b, has been investigated by comparing the efficiency of different lipases and acyl donors. Since esterification of (±)-9a and (±)-9b, occurred with low enantioselectivity (E 6 14) in the presence of the lipases considered, for preparative purposes we resorted, with success, to a double sequential kinetic resolution, using Lipozyme IM as the best catalyst. This approach enables us to obtain all the enantiomers with eeP95%. The absolute configuration of the new chiral N-acetyl cytosine derivative 9b was established by circular dichroism spectroscopy.
PREPARATION OF ISOXAZOLIDINYL NUCLEOSIDE ENANTIOMERS BY LIPASE-CATALYSED KINETIC RESOLUTION
CARNOVALE, CATERINA;IANNAZZO, Daniela;PIPERNO, Anna;
2009-01-01
Abstract
An efficient biocatalytic procedure to obtain chiral N,O-nucleoside derivatives consisting of a lipase-catalysed resolution of the corresponding racemates in organic solvent has been developed. Enantioselective esterification of thymine and cytosine derivatives, (±)-9a and (±)-9b, has been investigated by comparing the efficiency of different lipases and acyl donors. Since esterification of (±)-9a and (±)-9b, occurred with low enantioselectivity (E 6 14) in the presence of the lipases considered, for preparative purposes we resorted, with success, to a double sequential kinetic resolution, using Lipozyme IM as the best catalyst. This approach enables us to obtain all the enantiomers with eeP95%. The absolute configuration of the new chiral N-acetyl cytosine derivative 9b was established by circular dichroism spectroscopy.Pubblicazioni consigliate
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