The sugar cube: Network control and emergence in stereoediting reactions

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.