TOTAL SYNTHESIS OF POLYCYCLIC NATURAL PRODUCTS

尽管化学家们已经变得相当熟练地构建了少量 对于非常复杂的分子，我们通常不能制备出最理想的 以高效、实用和经济的方式使用有机化合物。 我们普遍不能构思和执行实践实验室 合成是我们科学的一个弱点。这是我们的长期目标 通过探索新的策略来解决这一不足 用于复杂有机结构的实验室合成。这些化合物 要合成的是自然界的分子--生物碱、碳水化合物、 异戊二烯类化合物和乙酸根素。其目的不仅仅是制造化合物， 但要以一种能教会我们一些关于 分子建造的建筑方面。具体的合成目标是 抗坏血素D、沙拉因A、圆柱酰胺、三色素A、石油脂类和 前丝球蛋白A 正在进行的这类研究的基本意义 这个项目是我们综合能力的提高。就是为了这个 我们发现新的有机结构并努力发现的原因 从商业上组装它们的非明显、有效的方法- 可用的构建块。作为合成化学家，我们的最终目标是 能够合成任何想要的有机分子，无论有多复杂， 以一种适合商业生产的方式。然而，许多人 我们选择的目标具有内在的生物重要性，并且 我们的合成研究可能具有直接的实际意义。其中 这些目标化合物是不一致蛋白D，它具有抗肿瘤活性 实体小鼠肿瘤，和前球蛋白A，一种重要的抑制因子 Ras法尼基蛋白转移酶(FTPase)。这些天然产品 是如此罕见，以至于没有足够的材料可以在体内进行全面的研究 评估。我们希望通过全合成来解决这个问题。

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.