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

ABSTRACT: Two novel and convenient routes to obtain enantiomerically enriched trans-?-aryl-?-hydroxy-?-lactones 5a-d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of ?,?-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-?-aryl-?-hydroxy-?-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-?-aryl-?-hydroxy-?-lactones 5a-d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.

SUBMITTER: Skrobiszewski A 

PROVIDER: S-EPMC6272857 | biostudies-other | 2016 Nov

REPOSITORIES: biostudies-other