Lipase Mediated Synthesis of (3R)-Stiripentol

Mohammed Farrag El-Behairy; Elisabeth Egholm Jacobsen

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.

Keywords: (3R)-Stiripentol, kinetic resolution, Candida antarctica lipase A, AMANO lipase AY30, high enantiomeric excess, chiral HPLC, cross metathesis

Abstract

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 5-vinylbenzo[d][1,3]dioxole.

Author Biography

Mohammed Farrag El-Behairy, Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Menoufiya, 32897, Egypt.