title: Total synthesis of 7'-desmethylkealiiquinone, 4'-desmethoxykealiiquinone, and 2-deoxykealiiquinone.
abstract: Synthetic approaches to the imidazonaphthoquinone core of kealiiquinone and related Leucetta-derived alkaloids are described. The polysubstituted benzimidazole framework can be constructed through intramolecular Diels-Alder reactions of propiolate-derived enynes followed by oxidation. Adjustment of the oxidation state of the thus formed lactone allows introduction of the 2,3-dihydroxybenzoquinone moiety through a presumed benzoin-like condensation between a phthaldehyde derivative and a masked glyoxal equivalent catalyzed by a cyanide ion. Oxidation of the C2-position can be accomplished through application of an operationally simple treatment of an imidazolium salt with bleach, thus producing the corresponding 2-imidazolone. Debenzylation of a late stage intermediate en route to kealiiquinone was compromised by concomitant O-demethylation upon treatment with triflic acid resulting in the formation of non-natural 7'-desmethylkealiiquinone. Other endgame strategies were evaluated; however, these efforts did not lead to completion of a synthesis of kealiiquinone but did provide access to other closely related analogues.
authors.affiliation: Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019-0065, United States.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Lima
authors.forename: Rasapalli
authors.initials: R
authors.lastname: Sivappa
authors.forename: Muhammed
authors.initials: M
authors.lastname: Yousufuddin
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Lovely
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D061565:Cycloaddition Reaction; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: C000592399:2-deoxykealiiquinone; C000592397:4'-desmethoxykealiiquinone; C573424:7'-desmethylkealiiquinone; D000470:Alkaloids; D007093:Imidazoles; D009285:Naphthoquinones