TOTAL SYNTHESIS OF POLYCYCLIC NATURAL PRODUCTS

尽管化学家们已经变得相当擅长于构建少量的 对于非常复杂的分子，我们通常无法制备出 以有效、实用和具有成本效益的方式生产有机化合物。 我们普遍无法设想和执行实际的实验室 综合是我们科学的弱点。这是长期目标 通过探索新的策略来解决这一缺陷 用于实验室合成复杂的有机结构。化合物 合成的是自然界的分子--生物碱，碳水化合物， 类异戊二烯和乙酸配基。其目的不仅仅是制造化合物， 而是以一种能教会我们一些新的东西的方式来做， 分子构建的建筑方面。特定的合成目标是 discorhabdin D、sarain A、cylindramide、tricolorin A、petrosins和 前体素A 这种研究的根本意义在于， 这个项目是我们综合能力的提高。正是由于这个 我们发现新的有机结构并努力发现 非显而易见的，有效的方法来组装它们， 可用的构建块。作为合成化学家，我们的最终目标是 能够合成任何所需的有机分子，无论多么复杂， 以适合商业生产的方式。但不少 我们选择的目标具有内在的生物学重要性， 我们的合成研究可能具有直接的实际意义。之间 这些目标化合物是discorhabdin D，其具有抗 实体小鼠肿瘤，和preussomerin A，一种重要的 酶Ras法尼基蛋白转移酶（FTTR）。这些天然产品 是如此罕见，没有足够的材料可用于全面的体内 评价通过全合成，我们希望解决这个问题。

Although chemists have become rather adept at constructing small amounts of very complicated molecules, we generally cannot prepare most desired organic compounds in an efficient, practical, and cost-effective manner. Our general inability to conceive and execute practical laboratory syntheses constitutes a frailty of our science. It is the long-term goal of this research to address this deficiency by exploring new strategies for the laboratory synthesis of complex organic structures. The compounds to be synthesized are molecules of Nature--alkaloids, carbohydrates, isoprenoids, and acetogenins. The intent is not just to make compounds, but to do it in a way that will teach us something new about the architectural aspect of molecule-building. Specific synthetic targets are discorhabdin D, sarain A, cylindramide, tricolorin A, the petrosins, and preussomerin A. The fundamental significance of the kind of research being carried out in this project is the improvement of our synthetic abilities. It is for this reason that we identify novel organic structures and strive to discover non-obvious, efficient methods to assemble them from commercially- available building blocks. Our ultimate goal as synthetic chemists is to be able to synthesize any desired organic molecule, no matter how complex, in a manner that would be amenable to commercial production. However, many of the targets we have chosen have intrinsic biological importance, and our synthetic research might have immediate practical importance. Among these target compounds are discorhabdin D, which has activity against solid murine tumors, and preussomerin A, an inhibitor of the important enzyme Ras farnesyl-protein transferase (FTPase). These natural products are so rare that insufficient material is available for full-scale in vivo evaluation. Through total synthesis we hope to remedy this problem.