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

• Published in: Molecules
• Main Authors: Andrzej Skrobiszewski, Witold Gładkowski, Gabriela Maciejewska, Czesław Wawrzeńczyk
• Format: Text
• Language: English
• Published: Multidisciplinary Digital Publishing Institute 2016
• Subjects: hydroxylactones; kinetic resolution; lipases; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/molecules21111552

Two novel and convenient routes to obtain enantiomerically enriched trans-β-aryl-δ-hydroxy-γ-lactones 5a–d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters 4a–d derived from enzymatically resolved allyl alcohols 1a–d, both enantiomers of hydroxylactones 5a–d 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 4a–d in the presence of m-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically active trans-β-aryl-δ-hydroxy-γ-lactones 5a–d 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 Candida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a–d and (+)-(4R,5S,6R)-propionates 6a–d, most of them with high enantiomeric excesses (92%–98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee = 89% and 84% for hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give access to both enantiomers of trans-β-aryl-δ-hydroxy-γ-lactones 5a–d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure–biological activity.