Stereoselective synthesis of the diunsaturated metabolites of valproic acid.
Two diene metabolites of valproic acid (VPA), (E)-2-n-propyl-2,4-pentadienoic acid and (E)-2-(1'-propenyl)-(E)-2-pentenoic acid, 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 and (Z)-2-(1'-propenyl)-(E)-2-pentenoic acid. 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.
Lee
R D
RD
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Kassahun
K
K
Abbott
F S
FS
D055598:Chemical Phenomena; D002621:Chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007536:Isomerism; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014635:Valproic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism*
D014635:Valproic Acid