Synthesis of stable isotope labeled analogs of the anti-hepatitis C virus nucleotide prodrugs PSI-7977 and PSI-352938

Article abstract of DOI:10.1080/15257770.2011.614308

In order to support bioanalytical LC/MS method development and plasma sample analysis in preclinical and clinical studies of the anti-hepatitis C-virus nucleotides, PSI-7977 and PSI-352938, the corresponding stable isotope labeled forms were prepared. These labeled compounds were prepared by addition reaction of the freshly prepared Grignard reagent ¹³CD₃MgI to the corresponding 2′-ketone nucleosides followed by fluorination of the resulting carbinol with DAST. As expected, these 2′-C-(trideuterated- ¹³C-methyl) nucleotide prodrugs showed similar anti-HCV activity to that of the corresponding unlabeled ones. Copyright Pharmasset, Inc..