Klussmann Martin, Iwamura Hiroshi, Mathew Suju P, Wells David H, Pandya Urvish, Armstrong Alan, Blackmond Donna G
Department of Chemistry, Imperial College, London SW7 2AZ, UK.
Nature. 2006 Jun 1;441(7093):621-3. doi: 10.1038/nature04780.
Ever since Pasteur noticed that tartrate crystals exist in two non-superimposable forms that are mirror images of one another--as are left and right hands--the phenomenon of chirality has intrigued scientists. On the molecular level, chirality often has a profound impact on recognition and interaction events and is thus important to biochemistry and pharmacology. In chemical synthesis, much effort has been directed towards developing asymmetric synthesis strategies that yield product molecules with a significant excess of either the left-handed or right-handed enantiomer. This is usually achieved by making use of chiral auxiliaries or catalysts that influence the course of a reaction, with the enantiomeric excess (ee) of the product linearly related to the ee of the auxiliary or catalyst used. In recent years, however, an increasing number of asymmetric reactions have been documented where this relationship is nonlinear, an effect that can lead to asymmetric amplification. Theoretical models have long suggested that autocatalytic processes can result in kinetically controlled asymmetric amplification, a prediction that has now been verified experimentally and rationalized mechanistically for an autocatalytic alkylation reaction. Here we show an alternative mechanism that gives rise to asymmetric amplification based on the equilibrium solid-liquid phase behaviour of amino acids in solution. This amplification mechanism is robust and can operate in aqueous systems, making it an appealing proposition for explaining one of the most tantalizing examples of asymmetric amplification-the development of high enantiomeric excess in biomolecules from a presumably racemic prebiotic world.
自从巴斯德注意到酒石酸盐晶体以两种不可重叠的形式存在，它们互为镜像——就像左手和右手一样——手性现象就一直吸引着科学家们。在分子层面，手性常常对识别和相互作用事件产生深远影响，因此对生物化学和药理学很重要。在化学合成中，人们投入了大量精力来开发不对称合成策略，以产生大量过量的左旋或右旋对映体的产物分子。这通常是通过利用影响反应进程的手性助剂或催化剂来实现的，产物的对映体过量（ee）与所用助剂或催化剂的ee呈线性关系。然而，近年来，越来越多的不对称反应被记录下来，其中这种关系是非线性的，这种效应可能导致不对称放大。长期以来，理论模型表明自催化过程可以导致动力学控制的不对称放大，这一预测现在已通过实验得到验证，并从机理上对自催化烷基化反应进行了合理化解释。在这里，我们展示了一种基于溶液中氨基酸的平衡固-液相行为产生不对称放大的替代机制。这种放大机制很稳健，可以在水性体系中起作用，这使其成为解释不对称放大最诱人的例子之一——从一个可能是外消旋的前生物世界中生物分子产生高对映体过量——的一个有吸引力的观点。
