Potential of synthetically modified surface exudate flavonoids from polygonum senegalense as antiplasmodial principles

Abstract

Polygonum senegalense produces surface exudates composed mainly of chalcones, flavanones and a homoisoflavanone. Synthetic transformation of some of the chalcones to new entities has been achieved via environmentally benign reactions ('green reactions'). Four chalcones were transformed into dihydrochalcones, flavanones and imines. Reaction of the pinostrobin chalcone (24) with selected primary amines resulted into two flavanone imine derivatives. The reaction was carried out at room temperature in water. These derivatives were obtained in yields of 45% for 7-methoxy-4-(methyl imino)-2-phenylchroman-5-o1 (1) and 78% for 4-(ethyl imino)-7-methoxy-2pheny Ichroman-5-ol (2). Four flavanones: 5-hydroxy-7,8-dimethoxyflavanone (3), alpinetin (4), 5-hydroxypinostrobin (5) and 5,7-dimethoxyflavanone (6) were prepared in aqueous media at the intervention ofNaOH catalysis at room temperature. This is a single step reaction that does not require use of organic solvents since isolation of the products was achieved via simple filtration with low-high chalcone-flavanone conversion achieved. Catalytic hydrogenation of the chalcones provided four dihydrochalcones: dihydropashanone (7), uvangolatin (8), 2' ,6' -dihydroxy-4' -methoxydihydrochalcone (9), lapathone (10). This was accomplished by bubbling hydrogen gas through solution of the respective chalcone with catalytic aid of palladium (5%) on charcoal to provide the dihydrochalcones in high yields (over 97% yields). Kostanecki acetylation of the synthesized dihydrochalcones; 7, 9 and 10 resulted to three compounds that include two acetylated enolates of the dihydrochalcones: 2-(1acetoxy-3-phenylprop-l-enyl)-4,5-dimethoxy-l ,3-phenylene diacetate (12), 2-( 1acetoxy-3-phenylprop-l-enyl)-5 methoxy 1,3-phenylenediacetate (11) and a homoisoflavone (3-benzyl-5, 7-dimethoxy-2-methyl-4H-chromen-4-one, 13). Nitro derivative of dihydrochalcone was prepared under mild nitrating conditions that include the use of nitric acid alone at temperatures below room temperature affording 2' ,6' -dihydroxy-4' -methoxy-3' -nitrodihydrochalcone (14). Some of the products formed were tested to assess their in vitro anti-plasmodial activities. These compounds showed moderate anti-plasmodial activities of ICso values: 9.32 and 11.6 ~M (7-methoxy-4-(methyl imino)-2-phenylchroman-5-ol, 1), 35.69 and 31.93 ~M (4-(ethyl imino)-7-methoxy-2-phenylchroman-5-ol, 2),8.7 and 14.5 ~M (7,8-dimethoxyflavanone, 3), 12.4 and 8.6 ~M (alpinetin,4), 8.0 and 6.1 ~M (6) against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains, respectively. Characterization of these compounds was guided mainly by their IH, 13C NMR and MS spectroscopic data.