合成路线1

The synthesis of [14C]-labeled pravastatin has been reported: The reaction of propylmagnesium bromide (I) with (14)CO2 gives [14C]-butyric acid sodium salt (II), which is converted to the corresponding acyl chloride (III) by reaction with oxalyl chloride. The condensation of (III) with 4(S)-benzyloxazolidin-2-one (IV) in THF yields the corresponding acylation product (V), which is methylated with sodium hexamethyldisilazide and methyliodide to afford a mixture of tautomeric N-[4(S)-benzyl-3-[2(R and S)-methylbutyryl]oxazolidin-2-ones, which are separated by preparative HPLC to obtain the optically pure diastereomer (VI). The oxidative cleavage of (VI) with H2O2 and LiOH, followed by acidification and treatment with NaOH, yields sodium 2(S)-methylbutyrate (VII), which is treated with oxalyl chloride to afford the corresponding acyl chloride (VIII). The condensation of (VIII) with 4(R)-(tert-butyldimethylsilyloxy)-6(R)-[2-[8(S)-hydroxy-2(S)-methyl-1,2,6,7,8,8a(R)-hexahydronaphth-1(S)-yl]ethyl]tetrahydropyran-2-one (IX) by means of 4-(dimethylamino)pyridine in CH2Cl2 gives the esterified compound (X), which is deprotected with tetrabutylammonium fluoride and acetic acid, yielding the hydroxylated pyrone (XI). Finally, this compound is submitted to an asymmetric hydroxylation with a culture broth of Mucor hiemalis MF-5021. The final product is extracted from the culture broth and purified by preparative HPLC to give a final radiochemical purity of 95%.