2,5 CYCLOHEXADIENONES IN NATURAL PRODUCTS SYNTHESIS

具体目标。下一个十年期间要实现六个主要目标 补助期;大部分拟议的化学取决于化学 2，5-环己二烯酮：1）双自由基的分子内环加成反应 由螺[2.5]辛-1，4-二烯-3-酮的光解产生的 开发这种新的级联工艺有望提供合成的 有机化学家用一个强大的战略，建设复杂的 碳环和杂环系统。拟议研究的关键是 发展了一种合成螺[2.5]辛-1，4- 二烯-3-酮衍生物。2)探索及 手性1-氧代-3-碘代环己烷的裂解反应研究进展 2，4-碳内酯有望提供有效的合成路线， 3，5-二取代和3，5，5-三取代丁烯内酯，2-烷基-4 羟基环己烯酮和5-取代的丁内酯都是单 对映体。百部生物碱（-）-的不对称全合成 stemoamide将证明一个重要的合成链接之间 芳香族羧酸衍生物和含有高度 取代的丁内酯环体系。3)预计，一个高效的 不对称合成（-）-文多灵的重要组成部分 抗癌药物长春碱和长春新碱将在 下一个补助期。该战略始于不对称的桦树 手性5-芳基-2-甲氧基苯甲酰胺的还原烷基化， 完全区域和立体选择性的分子内环加成 叠氮化物转化为2，5-环己二烯-1-酮，得到氮丙啶。4)合成 的有效的抗溃疡剂的外消旋和单一 将完成对映体修饰。机械信息 关于生成的烯醇化物的烷基化的非对映选择性， 从Birch还原3-苯并吡喃酮是本发明的长期目标。 study. 5)Zoanthamine络合物Zoanthamide的不对称合成 一种四环内有七个连续立体中心的类生物碱 核心结构将在下一个赠款期内进行。我们预计 以一种新的方法完成了（+）-石松碱的不对称全合成， 假设的串联自由基环化-氢转移的变体 并通过改进的策略， 已经开发用于核心三环的不对称合成 结构

Specific Aims. There are six major goals to be pursued during the next grant period; much of the proposed chemistry depends on the chemistry of 2,5-cyclohexadienones: 1) The intramolecular cycle-addition of biradicals generated from photolysis of spiro[2.5]octa-1,4-dien-3-ones will be developed. This new cascade process is expected to provide synthetic organic chemists with a powerful strategy for the construction of complex carbocyclic and heterocyclic ring systems. The key to the proposed study is the development of a general method of synthesis of spiro[2.5]octa-1,4- dien-3-ones from benzoic acid derivatives. 2) The exploration and development of fragmentation reactions of chiral 1-oxo-3-iodocyclohexane- 2,4-carbolactones is expected to provide efficient synthetic routes to 3,5-disubstituted and 3,5,5-trisubstituted butenolides, 2-alkyl-4 hydroxycyclohexenones, and 5-substituted butyrolactones all as single enantiomers. An asymmetric total synthesis of the stemona alkaloid (-)- stemoamide will demonstrate an important synthetic linkage between aromatic carboxylic derivatives and natural products containing a highly substituted butyrolactone ring system. 3) It is expected that an efficient asymmetric synthesis of (-)-vindoline component of the important carcinostatic drugs vinblastine and vincristine will be completed during the next grant period. The strategy begins with the asymmetric Birch reduction alkylation of a chiral 5-aryl-2 methoxybenzamide and involves the completely regio- and stereoselective intramolecular cycloaddition of an azide to a 2,5-cyclohexadien-1-one to give an aziridine. 4) Syntheses of the potent anti-ulcerogenic agent cassiol in racemic and single enantiomer modifications will be completed. Mechanistic information concerning the diastereoselectivities of alkylations of enolates generated from Birch reduction of 3-benzopyranones is the long-term goal of this study. 5) An asymmetric synthesis of zoanthamide a complex zoanthamine- type alkaloid with seven contiguous stereogenic centers in the tetracyclic core structure will be carried out during the next grant period. We expect to complete asymmetric total syntheses of (+)-lycopodine by way of a variant of the hypothetical tandem radical cyclization-hydrogen transfer and the melodinus alkaloid (+)-meloscine by modification of the strategy already developed for asymmetric synthesis of the core tricyclic structure.