title: Rapid cascade synthesis of poly-heterocyclic architectures from indigo.
abstract: The base-induced propargylation of the dye indigo results in the rapid and unprecedented one-pot synthesis of highly functionalized representatives of the pyrazino[1,2-a:4,3-a']diindole, pyrido[1,2-a:3,4-b']diindole and benzo[b]indolo[1,2-h]naphthyridine heterocyclic systems, with the last two reflecting the core skeleton of the anticancer/antiplasmodial marine natural products fascaplysin and homofascaplysins and a ring B-homologue, respectively. The polycyclic compounds 6-8, whose structures were confirmed through single-crystal X-ray crystallographic analysis, arise from sequential inter/intramolecular substitution-addition reactions, and in some cases, ring rearrangement reactions. Preliminary studies on controlling the reaction path selectivity, and the potential reaction mechanisms, are also described. Initial biological activity studies with these new heterocyclic derivatives indicated promising in vitro antiplasmodial activity as well as good anticancer activity. The chemistry described is new for the indigo moiety and cascade reactions from this readily available and cheap starting material should be more broadly applicable in the synthesis of additional new heterocyclic systems difficult to access by other means.
authors.affiliation: School of Chemistry, University of Wollongong, Wollongong, NSW, 2522, Australia.
authors.forename: Alireza
authors.initials: A
authors.lastname: Shakoori
authors.forename: John B
authors.initials: JB
authors.lastname: Bremner
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Willis
authors.forename: Rachada
authors.initials: R
authors.lastname: Haritakun
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keller
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; 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; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007203:Indigo Carmine / Q000737:chemistry*; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D011083:Polycyclic Compounds; D007203:Indigo Carmine