Chemoenzymatic Synthesis of trans-β-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures.

Two novel and convenient routes to obtain enantiomerically enriched -β-aryl-δ-hydroxy-γ-lactones - with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters - derived from enzymatically resolved allyl alcohols -, both enantiomers of hydroxylactones - were synthesized with high enantiomeric excesses (73%-97%). Configurations of the stereogenic centers of the synthesized compounds were assigned based on the mechanism of acidic lactonization of esters - in the presence of -chloroperbenzoic acid (-CPBA). An alternative method for the production of optically active β-aryl-δ-hydroxy-γ-lactones - was lipase-catalyzed kinetic resolution of their racemic mixtures by transesterification with vinyl propionate as the acyl donor. The most efficient enzyme in the screening procedure was lipase B from . Its application on a preparative scale after 6 h afforded unreacted (+)-(4,5,6)-hydroxylactones - and (+)-(4,5,6)-propionates -, most of them with high enantiomeric excesses (92%-98%). Resolution of lactone with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity ( = 89% and 84% for hydroxylactone and propionate , respectively). The elaborated methods give access to both enantiomers of β-aryl-δ-hydroxy-γ-lactones - with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.