Lipase Mediated Synthesis of (3R)-Stiripentol

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.