Stereoselective synthesis of the diunsaturated metabolites of valproic acid

Article abstract of DOI:10.1002/jps.2600780813

Two diene metabolites of valproic acid (VPA), (E)-2-n-propyl-2,4-pentadienoic acid (1) and (E)-2-(1'-propenyl)-(E)-2-pentenoic acid (2), were stereoselectively synthesized. Mesylate elimination in the final step to produce the unsaturation at position 2 was stereospecific for the (E)-configuration in the case of 2. Gas chromatography-mass spectroscopy and NMR were used to confirm the configuration of each diene including the minor isomers, (Z)-2-n-propyl-2,4-pentadienoic acid (9) and (Z)-2-(1'-propenyl)-(E)-2-pentenoic acid (18). Analysis of the dienes, as PFB derivatives by negative chemical ionization GC-MS from a serum extract of a patient on VPA therapy, revealed the presence of four peaks that in order of elution correspond to 9, 18, 1, and 2.