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Two δ‐iodo‐γ‐lactones and two γ‐iodo‐δ‐lactones substituted at the β‐position with phenyl or 4‐methylphenyl ring have been synthesized in both enantiomeric forms. The starting materials were enantiomerically enriched allyl alcohols with an (E)‐4‐phenylbut‐3‐en‐2‐ol system (ee in the range 88–99 %), which were obtained by lipase‐catalyzed transesterification. Alcohols were subjected to orthoacetate modification of the Claisen rearrangement. The high stereoselectivity of this reaction led to retention of (E)‐configuration of the double bond and complete transfer of chirality from the allyl alcohol to the benzylic position C‐3. As a result, chiral γ,δ‐unsaturated esters with retained configuration of the stereogenic center were produced. Their hydrolysis and iodolactonization afforded new enantiomers of iodolactones with high or excellent ee (97–99 %). Their configuration at C‐4 was a direct result of the configuration at C‐3 of the acid subjected to iodolactonization, whereas stereocenters at C‐5 and C‐6 were formed as a consequence of the reaction mechanism. For most of the synthesized isomers, the predicted configurations were established by X‐ray analysis. The presented chemoenzymatic pathway represents a useful strategy that can be applied in the asymmetric synthesis of variety of lactones from 4‐arylbut‐3‐en‐2‐ols.

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The results of biological tests showed that halogen atom removal significantly increased the antifeedant properties of γ-lactones with a p-methoxyphenyl substituent. Unsaturated lactones are most promising in the context of their possible industrial application as crop protection agents. Further structural modifications of lactones with aromatic rings are needed to find important structural factors increasing the antibacterial activity.

Eighteen racemic β-aryl-γ -lactones derived from simple aromatic aldehydes have been obtained in the chemical synthesis. Iodolactones (5c and 6c) were synthesized from (E)-4-(benzo [d][1 ,3 ]-dioxol-5 -yl)-but-3-en-2-one (1). Reductive dehalogenation of iodolactones 5a-c and 6a-c afforded γ -ethyl-γ -lactones (7a-c, 8a-c) whereas the unsaturated lactones (9a-c, 10a-c) were obtained by dehydrohalogenation of iodolactones. All synthesized lactones were fully characterized by spectroscopic data (NMR, IR, HRMS) and subjected to the tests on the antifeedant activity towards Tribolium confusum, Trogoderma granarium and Sitophilus granaries as well to the tests on the antifungal activity towards four Fusarium species. The biological tests allowed to find some relationships between the structure and biological activity of the compounds studied. γ -Ethyl-γ -lactones 7a-c, 8a-c and unsaturated lactones 9a-c, 10a-c were usually stronger antifeedants than their parent iodolactones 5a-c and 6a-c. trans-Iodolactones 6a-c were more active than cis isomers 5a-c both in antifeedant and antifungal assays. The structure of aromatic substituent was the key factor in antifungal activity. The lactones with benzo [d][1,3]dioxole ring (5c, 6c, 7c, 8c, 9c) were the most active whereas those with unsubstituted benzene ring exhibited almost no activity.

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.

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Hydrolysis of (±)-β-aryl-γ-ethylidene-γ-lactones by fungal strain Aspergillus ochraceus AM370 afforded (−)-(S)-γ-ethylidene-γ-lactones 2a–d and (+)-(R)-γ-ketoacids 3a–d. Enantiomeric purity of the unreacted lactones was strictly related to a size of an aryl substituent at C-4 of γ-lactone ring, with the highest ee (77%) obtained for the (−)-(S)-γ-ethylidene-γ-lactone possessing unsubstituted benzene ring (2a) and the lowest one (15%) determined for the (−)-(S)-γ-ethylidene-γ-lactone with bulky 1,3-benzodioxole system (2d). Lactones 2a–d, both racemic and enantiomerically enriched, as well as products of their hydrolysis showed varying degrees of feeding deterrent activity against lesser mealworm, Alphitobius diaperinus Panzer, which depended on the structure of the compound and the developmental stage of the lesser mealworm. In the case of adults, more active were γ-lactones 2a–d, compared with ketoacids 3a–d. Only in the case of lactone 2a was the effect of configuration of stereogenic center on the activity found. Particularly strong deterrents against this stage (T > 180) were racemic and (−)-(S)-γ-ethylidene-γ-lactone with p-methoxysubstituted phenyl ring (2c).