NATURAL PRODUCT SYNTHESES

该项目将产生新的有机合成方法和 充分检验生物活性天然产物的合成方法 产品和类似物。主题是激活和指导效果 过渡金属。新方法论的发展和应用 在复杂结构的形成中继续是强大的一部分 开发新药的途径。过渡金属提供了 开展精细和选择性碳-碳偶联的机会 反应，适用于立体声定义和高度功能化 目标。 有机过渡金属化学的两个方面将得到发展。 金属配位的乙烯基卡宾的重排是一个 从卡宾-金属与炔烃的反应开始，得到苯二酚 并导致耐人寻味的催化重排 环丙烯转变为更一般的系列芳香族结构。直接 乙烯基卡宾与金属的相互作用将通过相同的途径进行 一般的芳香族化合物，并可能提供直接证据 涉及多步骤途径。在第二个领域，将使用钯 促进杂环环的形成，伴随偶联 以CO和其他碳单元作为扩链步骤。特定的 在四诺霉素全合成及部分合成中的应用 并对其他抗生素的合成提出了建议。一位代表 与天然抗肿瘤药物相关的蒽醌将被构建 使用乙烯基卡宾/金属技术。此外，最后几个阶段 一种有效的蛋白质和核抑制因子--颗粒素的合成 合成，将完成有机镍的应用 中间体。

This project will generate new methods of organic synthesis and fully test the methods in the synthesis of biologically active natural products and analogs. The theme is the activating and directing effects of transition metals. The development of new methodology and application in formation of complex structures continues to be part of a powerful approach to the development of new drugs. Transition metals offer the opportunity to carry out delicate and selective carbon-carbon coupling reactions, appropriate for the stereo-defined and highly functionalized targets. Two aspects of organo-transition metal chemistry will be developed. Rearrangements of metal-coordinated vinyl-carbenes is a theme which begins with carbene-metal reactions with alkynes to give quinone derivatives and leads to intriguing catalytic rearrangements of cyclopropenes into more general series of aromatic structures. Direct interaction of vinyl carbenes with metals will lead via the same pathways to general aromatic compounds, and may give direct evidence for the multi-step pathway involved. In the second area, palladium will be used to promote the formation of heterocyclic rings, with concomitant coupling with CO and other carbon units as chain extension steps. Specific application in the total synthesis of tetronomycin as well as partial synthesis of other antibiotics are proposed. A representative anthraquinone related to the natural antitumor agents will be constructed using the vinyl-carbene/metal technology. In addition, the final stages of the synthesis of granaticin, a potent inhibitor of protein and nucleic synthesis, will be completed with an application of organo-nickel intermediates.