Hoffmann RW
Fachbereich Chemie Philipps-Universität Marburg Hans-Meerwein-Strasse, 35032 Marburg (Germany).
Angew Chem Int Ed Engl. 2000 Jun 16;39(12):2054-2070.
At the brink of the 21st century, chemistry is increasingly concerned with the function that molecules fulfil as drugs, receptors, or-as ensemble of molecules-as materials. The capability of compounds to fulfil such functions cannot sufficiently be described by using only the terms composition and configuration. A decisive role is played in addition by the conformation of the molecules, which serves as the link between molecular composition and molecular function. Expressions such as "active conformation" or "competent conformation" allude to this aspect. Chemists have to develop an understanding how a flexible molecule adopts the conformation (a distinct shape) which is optimal for the function in question and how this process can be controlled. On the outset of such considerations, we may ask how nature succeeded in the process of evolution to endow flexible molecules with a preference to adopt the conformation which is optimal for the function it has to serve. In this review, I report on how we have reached a crude level of understanding of conformation design in nature with reference to the class of polyketide natural products, how we developed these insights into a conformation design of open-chain compounds, and which applications are already in sight.
在21世纪即将来临之际,化学越来越关注分子作为药物、受体或作为分子集合体(如材料)所发挥的功能。仅用组成和构型这些术语,不足以描述化合物发挥此类功能的能力。此外,分子的构象起着决定性作用,它是分子组成与分子功能之间的纽带。诸如“活性构象”或“有效构象”等表述就暗示了这一方面。化学家们必须深入理解一个柔性分子是如何采用对相关功能而言最优的构象(一种独特形状),以及如何控制这一过程。在开始此类思考时,我们可能会问,在进化过程中,大自然是如何成功地使柔性分子倾向于采用对其必须发挥的功能而言最优的构象的。在这篇综述中,我将报告我们如何在聚酮类天然产物这一类别上,对自然界中构象设计有了初步的理解,如何将这些见解发展为开链化合物的构象设计,以及目前已经有哪些应用前景。