title: Synthesis of C- and O-prenylated tetrahydroxystilbenes and O-prenylated cinnamates and their action towards cancer cells.
abstract: Synthesis of the naturally occurred C- and O-prenylated tetrahydroxystilbenes and O-prenylated cinnamates was carried out by decarbonylative Heck reaction and selenium dioxide catalysed oxidation, respectively. In the decarbonylative Heck synthetic route, fusion of benzoyl chloride and styrene derivatives was catalysed by an N-heterocyclic carbene system generated in situ by palladium acetate and 1,3-bis(2,6-diisopropylphenyl)imidazolinium chloride to form a E-tetrahydroxystilbene derivative. Formation of allyl ether was subsequently carried out by reaction of the deprotected OH in the A phenyl ring of the stilbene with 3,3-dimethylallyl bromide and a base (sodium hydride) to form O-prenylated tetrahydroxystilbene derivatives. [1,5]-Rearrangement of the isoprenyl unit from O- to C-position in the A ring was carried out at elevated temperature in the presence of magnesium silicate (Florisil) to form the corresponding C-prenylated tetrahydroxystilbene. Formation of O-prenylated cinnamate was first carried out by base catalysed allyl ether formation between 3,3-dimethylallyl bromide and hydroxycinnamic acid methyl ester. The methyl group of the isoprenyl unit was subsequently oxidized using selenium dioxide to form a terminal hydroxyl group. The prenylated tetrahydroxystilbenes and cinnamate synthesized in this study were novel derivatives of piceatannol and methyl 4-(3'-methylbut-2'-enyloxy)cinnamate isolated from propolis in Kangaroo Island, South Australia. The synthetic compounds were tested against K562 cancer cells and potent growth inhibitory activity was observed for E-1-[5-hydroxy-3-methoxy-2-(3-methyl-2-butenyl)phenyl]-2-[4-hydroxy-3-methoxyphenyl]ethene, IC50 = 0.10 μM.
authors.affiliation: Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Koolaji
authors.forename: Abdallah
authors.initials: A
authors.lastname: Abu-Mellal
authors.forename: Van H
authors.initials: VH
authors.lastname: Tran
authors.forename: Rujee K
authors.initials: RK
authors.lastname: Duke
authors.forename: Colin C
authors.initials: CC
authors.lastname: Duke
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D008956:Models, Chemical; D015394:Molecular Structure; D054876:Prenylation; D011429:Propolis / Q000737:chemistry; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D013267:Stilbenes; C041525:3,3',4,5'-tetrahydroxystilbene; D011429:Propolis