Carder Hayden M, Occhialini Gino, Bistoni Giovanni, Riplinger Christoph, Kwan Eugene E, Wendlandt Alison E
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Chemistry, Biology and Biotechnology, University of Perugia, 06123 Perugia, Italy.
Science. 2024 Jul 26;385(6707):456-463. doi: 10.1126/science.adp2447. Epub 2024 Jul 25.
Stereochemical editing strategies have recently enabled the transformation of readily accessible substrates into rare and valuable products. Typically, site selectivity is achieved by minimizing kinetic complexity by using protecting groups to suppress reactivity at undesired sites (substrate control) or by using catalysts with tailored shapes to drive reactivity at the desired site (catalyst control). We propose "network control," a contrasting paradigm that exploits hidden interactions between rate constants to greatly amplify modest intrinsic biases and enable precise multisite editing. When network control is applied to the photochemical isomerization of hexoses, six of the eight possible diastereomers can be selectively obtained. The amplification effect can be viewed as a mesoscale phenomenon between the limiting regimes of kinetic control in simple chemical systems and metabolic regulation in complex biological systems.
立体化学编辑策略最近已能够将易于获得的底物转化为稀有且有价值的产物。通常，位点选择性是通过使用保护基团抑制不需要位点的反应性（底物控制）来最小化动力学复杂性，或者通过使用具有定制形状的催化剂来驱动所需位点的反应性（催化剂控制）来实现的。我们提出了“网络控制”，这是一种截然不同的范例，它利用速率常数之间的隐藏相互作用来极大地放大适度的内在偏差，并实现精确的多位点编辑。当网络控制应用于己糖的光化学异构化时，可以选择性地获得八种可能的非对映异构体中的六种。这种放大效应可以被视为简单化学系统中的动力学控制和复杂生物系统中的代谢调节这两种极限状态之间的中尺度现象。
