Practical Methods for Total Synthesis of Complex Natural Products

这项研究是由有机合成化学项目资助的。以经济有效的方式合成我们社会所需的复杂的新物质是本研究的目标。这是一项艰巨的挑战，需要相当的洞察力和独创性才能完成。自然界充满了具有复杂分子结构的有机化合物。通常，这些材料可能在数量上与它们的自然来源分离；更多的时候，它们不能。替代分离的另一种选择是合成--实验室用常见的材料制造。尽管在过去的半个世纪里，化学家们已经相当熟练地构建了少量非常复杂的分子，但他们通常无法以有效、实用和成本效益高的方式制备最理想的有机化合物。这种普遍无法构思和执行实际的实验室合成，构成了我们科学的一个弱点。这项研究的长期目标是通过发明复杂有机结构的实验室合成的新策略来解决这一不足。要合成的化合物是天然分子--生物碱和多异戊二烯类化合物。我们的意图不仅仅是制造一种化合物，而且要以一种将导致分子构建的结构方面的新东西的方式来做。恒定的目标是：(A)尽可能避免使用保护基团，以最大限度地减少所需的转化次数；(B)通过寻找在相同反应条件下可发生“级联”反应的方法，最大限度地减少所需的转化次数；(C)通过尽可能使用“低技术”来简化整个合成过程，而不是稀有昂贵的试剂。有待研究的具体体系有：岩黄素、沙拉宁-A、诺米宁、阿里斯通、二硫杂环己烷、鹿茸、金雀花素A和瑞香生物碱家族成员。

This research is being funded by the Organic Synthesis Chemistry Program. The synthesis of the complex new substances required by our society in a cost effective manner is the goal of this research. This is a daunting challenge that requires considerable insight and ingenuity to accomplish. Nature is replete with organic compounds of intricate molecular structure. Often these materials may be isolated from their natural sources in quantity; more often they cannot. The alternative to isolation is synthesis--laboratory manufacture from commonly available materials. Although chemists have over the last half-century become rather adept at constructing small amounts of very complicated molecules, they generally cannot prepare most desired organic compounds in an efficient, practical, and cost-effective manner. This 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 inventing new strategies for the laboratory synthesis of complex organic structures. The compounds to be synthesized are molecules of nature--alkaloids and polyisoprenoids. The intent is not just to make a compound, but to do it in a way that will lead to something new about the architectural aspect of molecule-building. The constant goals are: (a) to minimize the required number of tranformations by eschewing protective groups whenever possible, (b) to minimize the required number of transformations by finding ways in which "cascades" of reactions can occur under the same reaction conditions, (c) to simplify the total synthesis process by using, to the extent possible, "low-tech", rather than exotic, expensive reagents. The specific systems to be studied are: petrosin, sarain-A, nominine, aristone, dictyoxetane, velutinal, crinipellin A and members of the daphniphyllum alkaloid family.