2,5-CYCLOHEXADIENONES IN NATURAL PRODUCTS SYNTHESIS

下一个赠款期的一个主要主题将是探索 2，5-环己二烯-1-酮的化学。 这些多功能 合成中间体由容易获得的 苯甲酸衍生物。 综合方法论是 从这项调查中得出的结论将适用于 合成了几种医学和/或生物学上重要 天然产品。 对前手性2，5-二甲基苯并咪唑的分子内环加成反应 将探索环己二烯-1-酮。 其目的是指导 区域选择性加成到一个双键上， 辅助连接到C（4）。 具体来说，分子内 光化学2+2和2+4环加成反应，Diels-Alder 环加成，1，3-偶极环加成，有机铜酸盐 共轭加成环化，还原环化 适当取代的前手性2，5-环己二烯-1-酮将 研究了 分子内2+2光环加成反应将被应用 第一个对映选择性全合成的海洋 阿洛酮9-异氰基庚烷（59）。 氧烯丙基两性离子将通过以下物质的光重排产生： 5-环己二烯-1-酮，这些反应性中间体将 与烯烃、二烯进行分子内环加成， 有机叠氮化物。 其他光生化学的分子内反应 氧烯丙基两性离子与醇，胺，羰基， 膦亚胺、吡咯、吲哚和吡啶酮有希望 用于制备宽范围的杂环体系。 研究了4-丁烯基-2，5-二酮的分子内2+2光环加成反应。 环己二烯-1-酮将用于对映选择性的 衍生自柏木烯的二萜kempane-2（84 a）的构建 和Kempane 84 b。 另一种方法的kempane将利用 二甲基铜锂共轭加成环化4- 取代的2，5-环己二烯-1-酮。 第一对映选择性 进行所选石蒜烷生物碱的全合成。 石蒜碱（121）和相关生物碱具有抗病毒， 和短期的活动。 对映选择性全合成的最高度规定的 镇痛剂吗啡（129 b）和止咳药可待因（129 a） 也将在下一个资助期内开发。

A major theme of the next grant period will be the exploration of the chemistry of 2,5-cyclohexadien-1-ones. These versatile synthetic intermediates are constructed from readily available benzoic acid derivatives. The synthetic methodology that is developed from this investigation will be applied to the total synthesis of several medicinally and/or biologically important natural products. Enantioselective intramolecular cycloadditions to prochiral 2,5- cyclohexadien-1-ones will be explored. The aim is to direct regioselective addition to one double bond by the use of a chiral auxiliary attached to C(4). Specifically, the intramolecular photochemical 2+2 and 2+4 cycloadditions, the Diels-Alder cycloaddition, the 1,3-dipolar cycloaddition, the organocuprate conjugate addition-cyclization, and the reductive cyclization of suitably substituted prochiral 2,5-cyclohexadien-1-ones will be studied. The intramolecular 2+2 photocycloaddition will be applied to the first enantioselective total synthesis of the marine allomone 9-isocyanopupukeanane (59). Oxyallyl zwitterions will be generated by photorearrangement of 2,5-cyclohexadien-1-ones and these reactive intermediates will undergo intramolecular cycloadditions to olefins, dienes, and organic azides. Other intramolecular reactions of photogenerated oxyallyl zwitterions with alcohols, amines, carbonyl groups, phosphine imines, pyrroles, indoles, and pyridones hold promise for the preparation of a wide range of heterocyclic ring systems. The intramolecular 2+2 photocycloaddition of 4-butenyl-2,5- cyclohexadien-1-ones is to be used in an enantioselective construction of the cembrene-derived diterpenes kempane-2 (84a) and the kempane 84b. Another approach to the kempanes will utilize the lithium dimethylcuprate conjugate addition-cyclization of 4- substituted 2,5-cyclohexadien-1-ones. The first enantioselective total syntheses of selected lycorane alkaloids will be carried out. Lycorine (121) and related alkaloids exhibit antiviral, antineoplastic, and short-term hypotensive activity. Enantioselective total syntheses of the most highly prescribed analgesic agent morphine (129b) and the antitussive codeine (129a) also will be developed during the next grant period.