Alkaloids From The Fruits Of Flueggea Virosa

The plant Flueggea virosa(Roxb.ex Willd.)Voigt.,belonging to genus Flueggea(Euphorbiaceae),is a shrub widely distributed in eastern,southern,and southwestern of China.The whole plant of F.virosa could be used as a folk medicine for the treatment of rheumatism,cephalic eczema,pruritus,and injuries.Previous phytochemical investigations on the twigs,leaves,and roots of this plant had led to the isolation of a number of indolizidine alkaloids,known as Securinega alkaloids.However,to date,studies about the alkaloid constituents of the fruits of F.virosa were very rare.During our ongoing searching for structurally unique and bioactive interesting alkaloids from the plants of genus Flueggea,our group had reported the isolation of diverse Securinega alkaloids with unusual skeletons from the roots,twigs,and leaves of F.virosa.Recently,a novel tryptophan-derived alkaloid has been isolated from the fruits of F.virosa,suggesting that much more complex alkaloids with even wider structural diversity might present in this plant.Prompted by our previous findings,this thesis carried out a further phytochemical investigation on the total alkaloid fraction of the fruits of F.virosa.As a result,total twenty-eight alkaloids were isolated via various chromatographic methods,and their structures were elucidated by extensive spectroscopic techniques as well as computational method.They are fluevirosine A(FVA-1),fluevirosine D(FVA-2),flueggenine A(FVA-3),flueggenine C(FVA-4),flueggenine D(FVA-5),fludenine A(FVA-6),fluphenylamine A(FVA-7),norsecurinine(FVA-8),virosecurinine(FVA-9),viroallosecurinine(FVA-10),ent-phyllanthidine(FVA-11),secu?amamine E(FVA-12),(+)-virosine B(FVA-13),(–)-securinol A(FVA-14),(+)-2-episecurinol(FVA-15),fluespirosine A(FVA-16),1H-pyrido[3,4-b]indole-1-methanol(FVA-17),3-hydroxymethyl-?-carboline(FVA-18),strychnocarpine(FVA-19),1-methyl-1,2,3,4-tetrahydro-?-carboline(FVA-20),2-methyl-1,2,3,4-tetrahydro-?-carboline(FVA-21),ethyl dioxindole-3-acetate(FVA-22),N-methyltryptamine(FVA-23),N,Ndimethyltryptamine(FVA-24),3-methoxycarbonylindole(FVA-25),seculactine A(FVA-26),flueindoamine A(FVA-27),and donaxanine(FVA-28),respectively.Among them,compounds FVA-6,FVA-7,FVA-16,FVA-26,and FVA-27 are five new alkaloids.Notably,FVA-6 is the first Securinega alkaloid comprising dihydrovirosecurinine and adenine units.And FVA-16 is a novel alkaloid possessing a unique spiro[oxindoline-3,1'-pyrrolizine] skeleton,which represents the first example of this class of alkaloids from natural source.Moreover,FVA-26 is the first quinolizidine alkaloid from the genus Flueggea,and FVA-27 represents the first example of pyridoindole alkaloid from this genus.In addition,the chiral HPLC separation of(±)-FVA-17,(±)-FVA-20,(±)-FVA-27,and(±)-FVA-28 afforded four pairs of optically pure enantiomers,respectively.The absolute configurations of these enantiomers were elucidated on the basis of quantum chemical calculations.The hypothetical biosynthetic pathways of the novel alkaloids were also discussed,which implied that besides the commonly biogenetic precursors of Securinega alkaloids(lysine,tyrosine,and ornithine),tryptophane and phenylalanine were also employed as the building blocks in the biosynthesis of the alkaloids in F.virosa.