The stories of santonin and santonic acid
The stories of santonin and santonic acid
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DOI：
10.1002/anie.200390318
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Birladeanu, L
中科院分区：
文献类型：
--
作者：
Birladeanu, L
自世纪中期以来，有机化学的一个主要目标就是确定天然产物的结构。对天然产品的迷恋可以追溯到远古时代，受到精致的颜色，诱人的气味和通常非常显着的生理效应的刺激。1859年以前，结构的概念并不存在。只有在布特洛夫、库伯、凯库洛夫和货车t霍夫发明了结构理论之后，结构决定才成为一个可以设想的目标。已故的罗伯特·伯恩斯·伍德沃德（Robert Burns Woodward）用这样的话赞美了结构理论的创立：“分子的结构和形式为所有形式的物质的分化提供了根本基础，这一发现是人类最伟大的发现之一。[1]今天的化学家很难想象，在红外光谱、核磁共振光谱、质谱和终极武器X射线晶体学等强大的物理工具出现之前，极其复杂的结构是如何被确定的。但是，在结构测定的实践中，可以区分出两个早期阶段，并在山道宁及其挑衅性衍生物山道宁酸的历史中得到例证。在第一个时期，大约在1870年到1900年之间，表征取决于熔点，沸点，密度，折射率和光学活性。元素分析提供了经验公式。凝固点降低，沸点升高提供分子量。主要的结构见解完全来自化学转化和降解成更简单的，已经认识到的结构。从这种转变中得出的推论是基于类比、经验方法和直觉。根据巴斯德的说法，当科学进步的重要性被正确认识时，机遇是科学进步的重要因素。在第二个时期，随着反应机理理论的迅速发展，从化学转化中推导出的结构推论可能会受到一种新的批判性评价。在上个世纪之交，有机化学开始从一门经验的、本质上是分类学的科学迅速转变为一门被反应发生机理的理论大大增强的科学。真正的先驱者，亚瑟·拉普沃思和罗伯特·罗宾逊爵士，标志着这一开端，但在这些新见解的力量被广泛纳入天然产物化学家的思想之前，许多年已经过去了。在这两个时期，结构假说都通过合理的合成以及合成产物和天然产物的同一性的确立而得到了最终的证实，山冬宁及其转化产物山冬酸的故事就反映了这些早期阶段的作用。它不仅揭示了第一阶段思维的局限性如何完全阻碍了结构的成功解析，而且揭示了新的机制概念如何将光明带入了原本无法穿透的黑暗。
Since the middle of the 19th century, a major goal of organic chemistry has been the determination of the structure of natural products. Fascination with naturally occurring products dates back to time immemorial, stimulated by exquisite colors, seductive smells, and often very remarkable physiological effects. Before 1859 the concept of structure did not exist. Only with the invention of the structural theory by Butlerov, Couper, KekulØ, and van t Hoff could structure determination become a conceivable goal. The late Robert Burns Woodward extolled the creation of structural theory in these words,“The discovery that the structure and form of molecules provide the fundamental basis for the differentiation of all forms of matter was one of man s greatest discoveries”.[1] Today's chemists can scarcely imagine how structures of great complexity were determined before the availability of the powerful physical tools of IR and NMR spectroscopy, mass spectrometry, and the ultimate weapon, X-ray crystallography. But two earlier stages in the practice of structure determination can be distinguished, and are exemplified in this history of santonin and its provocative derivative, santonic acid. In the first period, between around 1870 to 1900, characterization depended on melting points, boiling points, densities, refractive indices, and optical activity. Elemental analysis provided empirical formulas. Depression of freezing point, elevation of boiling point provided molecular weights. Major structural insights came exclusively from chemical transformations and degradations into more simple, already recognized structures. Inferences from such transformations were based on analogy, empirical approaches, and intuition. Chance—according to Pasteur, an important ingredient in scientific advances when its significance is correctly perceived—played its role. In the second period, as theories of the mechanisms of reactions were rapidly developing, inferences about structure derived from chemical transformations could be subjected to a new type of critical evaluation. At the turn of the last century, organic chemistry began its rapid change from an empirical, essentially taxonomic science into one dramatically enhanced by theories of the mechanism by which reactions occurred. True pioneers, Arthur Lapworth and Sir Robert Robinson, mark the beginning, but many years would pass before the powers of these new insights would be widely incorporated into the thinking of natural-product chemists. During both periods, structural hypotheses received their final verification through rational synthesis, and the establishment of the identity of the synthetic and the natural product.The story of santonin and its transformation product, santonic acid, captures the working of these earlier periods. It not only reveals how the limitations of the thinking in the first period could totally block a successful resolution of structure, but how the new concepts of mechanism could bring light into an otherwise impenetrable darkness.