Absolute configuration of the four stereoisomers of valnoctamide (2-ethyl-3-methyl valeramide), a potentially new stereospecific antiepileptic and CNS drug

摘要: Abstract Valnoctamide (2-ethyl-3-methyl valeramide, Nirvanil®, VCD), a mild tranquilizer endowed with anticonvulsant properties, exhibits diastereoselective and enantioselective pharmacokinetics in healthy subjects epileptic patients. The purpose of this paper is to assign the absolute configuration four VCD stereoisomers describe stereoselective synthesis used prepare two-key stereoisomers. We have synthesized two out stereoisomers, high diastereomeric excess, by different synthetic methods. In both methods (S) at C-3 was fixed synthesizing (S)-3-methyl valeric acid from l -isoleucine. first method mixture (2RS,3S)-VCD prepared. This gave one diastereomers via repeated crystallizations, its (2R,3S)-VCD, established X-ray crystallography using single crystal. all separated chiral gas chromatography, on basis enantiomeric correlations. order assess pharmacodynamic properties VCD, be synthesized. Stereoselective (2R,3S)-VCD (2S,3S)-VCD accomplished oxazolidinone auxiliaries. These were obtained 99.6% excess.