Microbial Hydrolysis of Racemic ß-Aryl-γ-ethylidene-γ-lactones and Antifeedant Activity of the Products against Alphitobius diaperinus Panzer.

Hydrolysis of (±)-ß-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).

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

Two novel and convenient routes to obtain enantiomerically enriched trans-ß-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-ß-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-ß-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.

Lactones 46. Synthesis, antifeedant and antibacterial activity of γ-lactones with a p-methoxyphenyl substituent.

BACKGROUND: Lactones are well known for their biological activity. Grosheimin and repin are potent deterrents against storage pests. The unsaturated lactones have exhibited a wide spectrum of antibacterial activity. In our study we focused on the synthesis and evaluation of the biological activity of anisaldehyde derivatives containing lactone function. RESULTS: Four new lactones were synthesized in one-step reductive dehalogenation or dehydrohalogenation reactions. These compounds, together with halolactones synthesized earlier, were tested for their antifeedant activity towards Sitophilus granaries, Trogoderma granarium and Tribolium confusum. The results of the tests showed that the highest activity, comparable with that of azadirachtin, towards all tested pests (total coefficient of deterrence 143.3-183.9) was observed for lactone with a vinyl substituent. The antibacterial activity of these compounds was also evaluated. The most potent lactone was active towards gram-positive bacteria strains. CONCLUSIONS: 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.