RESUMEN

Some commercial batches of dichloroacetic acid (DCA) contain traces of chloral (trichloroacetaldehyde). Using such DCA to effect detritylation during solid-phase oligonucleotide synthesis results in the formation of a family of process impurities in which the atoms of chloral (Cl3CCHO) are incorporated between the 5'-oxygen and phosphorus atoms of an internucleotide linkage. The structure was elucidated by HPLC with UV and MS detection, digestion of the oligonucleotide, synthesis of model compounds, and 1H and 31P NMR spectroscopy. By understanding the chemistry behind its formation, we are now able to limit levels of this impurity in synthetic oligonucleotides by limiting chloral in DCA.

Asunto(s)

Hidrato de Cloral/análogos & derivados , Oligonucleótidos/química , Hidrato de Cloral/análisis , Hidrato de Cloral/química , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Contaminación de Medicamentos , Espectrometría de Masas , Estructura Molecular , Oligonucleótidos/síntesis química