title: Diversity oriented synthesis of a vinblastine-templated library of 7-aryl-octahydroazonino[5,4-b]indoles via a three-component reaction.
abstract: A vinblastine-templated library of 7-aryl-octahydroazonino[5,4-b]indoles was prepared by a three-component reaction from indolizino[8,7-b]indoles, chloroformates, and activated arenes via a chloroformate mediated fragmentation of the indolizinoindole nucleus followed by insertion of an activated arene. In addition to N3-carbamoyl-7-aryl-octahydroazonino[5,4-b]indoles prepared in one step, a wide range of N3-substituted substrates were synthesized in one pot via the derivatization of a versatile N3-H-azonino[5,4-b]indole intermediate generated in situ by application of the same strategy. A subset of 308 compounds out of a virtual library of 3216, representing 13 different chemotypes, was prepared by high throughput solution-phase synthesis and subsequently purified by mass-triggered high performance liquid chromatography (HPLC). A total of 188 compounds with a minimum purity of 80% by UV214 nm and 85% by evaporative light scattering detection (ELSD) was isolated for primary screening.
authors.affiliation: Department of Chemistry, ArQule Inc , 19 Presidential Way, Woburn, Massachusetts 01801, United States.
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Fokas
authors.forename: Mira
authors.initials: M
authors.lastname: Kaselj
authors.forename: Yuko
authors.initials: Y
authors.lastname: Isome
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D054852:Small Molecule Libraries; D014747:Vinblastine / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007211:Indoles; D054852:Small Molecule Libraries; D014747:Vinblastine