Chemistry and biosynthesis of isoprenylated flavonoids from Japanese mulberry tree

Many isoprenylated flavonoids have been isolated from Japanese mulberry tree (Moraceae). Among them, kuwanons G (1) and U (2) were the first isolated active substances; exhibiting a hypotensive effect. These compounds are considered to be formed through an enzymatic Diels-Alder type reaction between an isoprenyl protion of an isoprenylphenol as the diene and an a, beta-double bond of chalcone Lis the dienophile. The absolute configurations of these Diels-Alder type adducts were confirmed by, three different methods. The stereochemistries of the adducts were consistent with those of ones in the Diels-Alder reaction involving exo- and endo-addition. Some strains of Morus alba callus tissues have a high productivity of mulberry Diels-Alder type adducts, such as chalcomoracin (3) and kuwanon J (4). The biosynthetic studies of the mulberry Diels-Alder type adducts have been carried out with the aid of the cell strain. Chalcomoracin (3) and kuwanon J (4) were proved to be enzymatic Diels-Alder type reaction products by the administration experiments with O-methylchalcone derivatives. Furthermore, for the isoprenoid biosynthesis of prenylflavonoids in Moras alba callus tissues by administration of [1,3-C-13(2)]- and [2-C-13]- glycerol, a novel way through the junction of glycolysis and pentose-phosphate cycle was proved. Two independent isoprenoid biosynthetic pathways, that for sterols and that for isoprenoidphenols, operate in the Morus alba cell cultures. The former is susceptible to compactin (ML-236) and the latter resists to compactin hi the cell cultures, respectively.