The synthesis of carbon-14 labeled pravastatin

An asymmetric route to [14C]β-hydroxycompactin 1 bearing the (S)-2-methyl-[1-14C]butanoate side chain has been developed. Methylation of [N-[1-14C]butyryl]-4-(S)-phenylmethyl-2-oxazolidinone 4 afforded a 95:5 mixture of diastereomeric [N-(S,R)-2-methyl-[1-14C]butyryl]-4-(S)-phenylmethyl-2-oxazolidi nones 5,6 which were separated by preparative HPLC. Oxidative cleavage of 5 afforded optically pure (S)-2-methyl-[1-14C]butanoic acid. Acylation of alcohol 9 with optically pure (S)-2-methyl-[1-14C] butyryl chloride afforded ester 10. Removal of the silyl ether produced diastereomerically pure compactin 11. Hydroxylation was carried out by biotransformation with Mucor hiemelus to afford diastereomerically pure [[1-14C]butanoate]β-hydroxycompactin, [14C]Pravastatin 1. (Author)