American Chemical Society
jo4027337_si_001.pdf (8.89 MB)

Total Synthesis of 7′-Des­methyl­keali­iquinone, 4′-Des­methoxy­keali­iquinone, and 2‑Deoxy­keali­iquinone

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journal contribution
posted on 2015-12-17, 01:09 authored by Heather M. Lima, Rasapalli Sivappa, Muhammed Yousufuddin, Carl J. Lovely
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.