Department of Chemistry and Biochemistry, University of Texas at Arlington , Arlington, Texas 76019-0065, United States.
J Org Chem. 2014 Mar 21;79(6):2481-90. doi: 10.1021/jo4027337. Epub 2014 Mar 3.
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.
描述了 kealiiquinone 和相关 Leucetta 衍生生物碱的imidazonaphthoquinone 核心的合成方法。通过丙炔酸衍生的烯炔的分子内 Diels-Alder 反应，然后进行氧化，可以构建多取代的苯并咪唑骨架。通过假定的苯甲醛衍生物和掩蔽的乙二醛等价物之间的安息香缩合（由氰离子催化），可以在形成的内酯中引入 2,3-二羟基苯醌部分，从而调节如此形成的内酯的氧化态。可以通过用漂白剂处理咪唑鎓盐的操作简单的处理来完成 C2-位置的氧化，从而生成相应的 2-咪唑啉酮。在通往 kealiiquinone 的后期中间体的脱苄基化过程中，由于用三氟甲磺酸处理会发生同时的 O-脱甲基化，导致形成非天然的 7'-去甲基 kealiiquinone。评估了其他终局策略；然而，这些努力并没有导致 kealiiquinone 的合成完成，但确实提供了其他密切相关的类似物的途径。
