title: Chemoenzymatic Synthesis of trans-β-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures.
abstract: Two novel and convenient routes to obtain enantiomerically enrichedtrans-β-aryl-δ-hydroxy-γ-lactones5a-dwith potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters4a-dderived from enzymatically resolved allyl alcohols1a-d, both enantiomers of hydroxylactones5a-dwere 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 esters4a-din the presence ofm-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically activetrans-β-aryl-δ-hydroxy-γ-lactones5a-dwas 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 fromCandida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones5a-dand (+)-(4R,5S,6R)-propionates6a-d, most of them with high enantiomeric excesses (92%-98%). Resolution of lactone5dwith bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee= 89% and 84% for hydroxylactone5dand propionate6d, respectively). The elaborated methods give access to both enantiomers oftrans-β-aryl-δ-hydroxy-γ-lactones5a-dwith the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.
authors.affiliation: Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, Wrocław 50-375, Poland. andrzej.skrobiszewski@gmail.com.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Skrobiszewski
authors.affiliation: Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, Wrocław 50-375, Poland. glado@poczta.fm.
authors.forename: Witold
authors.initials: W
authors.lastname: Gładkowski
authors.affiliation: Central Laboratory of the Instrumental Analysis, Wrocław University of Technology, Wybrzeże Wyspiańskiego 27, Wrocław 50-370, Poland. gabriela.maciejewska@pwr.edu.pl.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Maciejewska
authors.affiliation: Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, Wrocław 50-375, Poland. czeslaw.wawrzenczyk@up.wroc.pl.
authors.forename: Czesław
authors.initials: C
authors.lastname: Wawrzeńczyk
mesh_terms: D055162:Biocatalysis; D005656:Fungal Proteins / Q000378:metabolism*; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008049:Lipase / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D005656:Fungal Proteins; D007783:Lactones; D008049:Lipase; C431349:lipase B, Candida antarctica
keywords: hydroxylactones; kinetic resolution; lipases