Racemic stiripentone was synthesised from piperonal and pinacolone and reduced to the alcohol stiripentol, which was obtained in high yield. Kinetic resolution of stiripentol catalysed by lipase A from Candida antarctica via esterification with vinyl butanoate has been performed with an E-value of 24. This allowed isolation of (3S)-stiripentol with an enantiomeric excess (ee) of 86% and the corresponding (3R)-butanoate with an ee of 87%. Enzymatic hydrolysis of the ester product gave (3R)-stiripentol with an ee of 94%. Additionally, a novel one-pot two-step pathway for the synthesis of 5-vinylbenzo[d][1,3]dioxole starting from (E)-3,4-dihydroxycinnamic acid has been developed. Lipase catalysed esterification of 4,4-dimethylpent-1-en-3-ol afforded (R)-(+)-4,4-dimethylpent-1-en-3-ol and an ee >99% of (3R)-stiripentol was obtained via cross metathesis of this compound coupled with 5vinylbenzo[d][1,3]dioxole.
Mohammed Farrag El-Behairy
Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufiya, 32897, Egypt
Elisabeth Egholm Jacobsen
Department of Chemistry, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.