Study On Synthesis And Bioactivity Of6,7-Methylenedioxy-4-Chromanone Derivatives

Chromanones, as a class of natural products, have been found extensively in flowers,barks, roots and stems of many plants, as well as in the fermentation products of marine fungi.Being isolated simultaneously along with coumarins, isoflavonoids, alkaloids and polyketides,they were considered as metabolism modulators in cooperation with each other. Thus far,plenty of novel chromanones have been achieved via isolation or synthesis, of which theprominent antifungal, insecticidal, antioxidant, anticancer, anti-inflammation and anti-HIVactivities raised our interest to further explore the potential of their derivatives likeantioxidant, antifungal and insecticidal activities in agricultural application.Thirty-three6,7-methylenedioxy-4-chromanones have been synthesized fromsesamol, following etherification, Friedel-Crafts acylation, Mannich reaction, Hofmannelimination, adol condensation and oximation. Spectroscopic methods including1H NMR,¹³CNMR, MS and IR were used to elucidate the structures.Good in vitro antifungal activity occurred in d, e1, e6, e10, e14, e16and f.Meanwhile, it is notable that e1, e2, e8, e11, e14performed better brine shrimp lethality thancommercial nicotinyl pesticide Imidacloprid with LC₅₀between0.95μg/mL to3.22μg/mL.In terms of antioxidant activity, moderate activity was found in e16, and to our surprise, the[DPPH·] free radical scavenging activity of e32overwhelmed ascorbic acid with its EC50at1.83μg/mL.In our effort to clarify the relationship between structure and bioactivity, quantumchemistry computation was used to determine the physicochemical properties. ClogP wasfound to have the most predominant contribution in antifungal activity; however, otherproperties also affect the transportation and docking capacities in organisms. There is nocorrespondence between brine shrimp lethality and physicochemical properties, but theelectrostatic potential of e1may give a proposed answer to its potency against fungi and brineshrimps, since unsubstituted C=C double bond increases its nucleophilic addition withelectron-abundant receptors. Antioxidant mechanism of e32should be owed to the presenceof phenyl hydroxy, p-substituted conjugated side chain, o-substituted electron donating group and internal H-bond, working together to stablized the radical and gift its even more potentantioxidant activity than ascorbic acid.