Studies On The Synthesis And Antifungal Activities Of Dihydroflavone Sulfone And Benzothiazole Derivatives

In recent years,due to the enhancing awareness of environmental protection and concept of green chemistry,research and development of pesticide with low toxicity and high efficiency has become an important research topic.Organic phosphorus pesticides of high toxicity are gradually replaced by a number of novel pesticide varieties containing heterocyclic structures and sulfone structures,exhibiting high efficiency,low toxicity and low residue.Moreover,it is very attractive to construct new pesticides with two or more functional groups combining heterocyclic structures or sulfone structures.On the other hand,free radical transformation has become one of the most active research hotspots in the field of organic synthetic chemistry.Due to the high activity and short existence time of free radicals,its addition reaction with unsaturated hydrocarbons could occur easily,which could enable the construction of chemical scaffolds that are difficult to achieve with other methods,such as chiral quaternary-carbon center containing compounds.In recent years,cascade difunctionalization of alkenes involving free radical process for the formation of heterocyclic compounds have appealed extensive attentions owing to its prominent advantages in step-and-atom efficiency.In addition,radical insertion reactions into isonitriles have emerged as an efficient and powerful strategy for the construction of nitrogen heterocycles,such as phenanthridines,indoles,quinolines,quinoxalines,and isoquinolines.Based on a large number of literatures,a series of novel functional heterocyclic or sulfone-cotaining compounds are developed in this paper with antifungal activity test carried out at the same time.Rigorous experiments are performed followed by data analysis,product characterization and mechanical study The details are summarized as follows:1.Decarboxylative difunctionalization of alkenes to dihydroflavone derivativesDecarboxylative cross-coupling reactions to construct C-C and C-X bonds have attracted a great deal of current interests due to their potential advantages,such as using readily available,stable,and low-cost carboxylic acids,extruding of nontoxic CO2 gas as by-product,and high selectivity.In this paper,a silver nitrate-catalyzed cascade decarboxylative radical addition/cyclization of alkenes and a-oxocarboxylic acids was established with aldehydes as the radical acceptors,furnishing dihydroflavonoid derivatives as products.The compounds were isolated and characterized by 1H-NMR,13C-NMR,31P-NMR,HR-MS,IR,m.p.,among which 23 compounds were new and have not been reported before.On the basis of the experimental facts and some previous reports,the transformation occurs through free radical pathway using aldehydes as carbon radical acceptors.2.Synthesis of sulfone-containing compounds by benzyl functionalization of phenol derivativesSeveral ways are known to introduce sulfone skeletons into lead compounds:the first is the oxidation of thioethers,with hydrogen peroxide(H2O2),potassium persulfate(K2S2O8)or m-chloroperoxybenzoic acid(m-CPBA)commonly used as oxidants.The second method is the nucleophilic substitution reaction of halogenated molecular and sulfone-based precursors.The third route to build sulfonyl-containing compounds is transition-metal catalyzed direct C(sp2)-H sulfonylation assisted by directing-groups.The last strategy is based on the addition of sulfonyl radicals to unsaturated systems such as alkynes and alkenes,which provide a straightforward protocol to construct corresponding sulfonyl-containing compounds.In this section,an alkene intermediate was formed through the tautomerism of the substrate initiated by oxidant,and its the subsequent sulfonation or sulfonation/peroxidation reaction can be achieved by controlling the stoichiometric ratio of the oxidant.3.Free radical cascade reaction of functionalized isocyanides toward 2-substituted benzothiazole derivativesIsocyanides as versatile building blocks have been widely applied in the synthesis of numerous nitrogen-containing compounds that are key motifs in biological and medicinal chemistry.Inherently,isocyanides serve as not only nucleophiles,but also efficient radical acceptors to produce imidoylradical intermediates for subsequent reactions.This cycloadditions share acommon pathway involving the attack of imidoyl radicals to unsaturated carbon atoms.It is reasoned that the addition of imidoyl radicals to vicinal heteroatoms would provide novel and expeditious approach to construct polyhetero compounds.The retard in this field might be attributed to the challenges as follows:1)Nucleophilic addition of "free" heteroatoms(-OH,-NH2,-SH,etc.)to isocyanides renders carbene intermediates,resulting in inhibition of a radical process.2)The "leaving moiety"on heteroatoms must be easily cleavaged upon imidoyl radicals attack,but inert to initially generated radical species.4.Antifungal activity determinationTo test antifungal activity of some sulfone-containing or 2-substituted benzothiazole compounds which have never been reported in literatures,the inhibitory rate of 78 compounds to Botrytis cinerea,Altemaria solani,Fusarium graminearum,Rhizoctonia solani and Alternariamali were determined through growth rate method;the toxicity of some compounds to Botrytis cinerea,Rhizoctonia solani and Alternariamali were also determined;the structure-activity relationship was discussed based on the antifungal activity of the target compounds.The results showed that most of the 82 compounds had different degrees of activity to the tested fungi.The toxicity of some compounds to the tested funngi was determined.The EC50 of the compounds A10、A18、B4 and C21 to Rhizoctonia solani was 10.02 μg/mL,15.06 μg/mL,14.20 μg/mL,1.13 μg/mL respectively;the EC50 of the compound B3、B14、B15、C1、C2、C7、C13、C17 and C21 to Botrytis cinereal was 18.26 μg/mL、4.38 μg/mL、13.13 μg/mL、93.8 μg/mL、64.4 μg/mL、90.3 μg/mL、143.2 μg/mL、27.41 μg/mL、18.34 μg/mL respectively;the EC50 of C13 to Alternariamali was 22.3μg/mL,which means the activity is worse than the control agent,but also showed better activity.The compounds used in the activity test showed a certain activity,which could provide a new direction for creation of new pesticides.