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.

Selective Axial-to-Equatorial Epimerization of Carbohydrates.

Radical-mediated transformations have emerged as powerful methods for the synthesis of rare and unnatural branched, deoxygenated, and isomeric sugars. Here, we describe a radical-mediated axial-to-equatorial alcohol epimerization method to transform abundant glycans into rare isomers. The method delivers highly predictable and selective reaction outcomes that are complementary to other sugar isomerization methods.

A Unified Strategy to Access 2- and 4-Deoxygenated Sugars Enabled by Manganese-Promoted 1,2-Radical Migration.

The selective manipulation of carbohydrate scaffolds is challenging due to the presence of multiple, nearly chemically indistinguishable O-H and C-H bonds. As a result, protecting-group-based synthetic strategies are typically necessary for carbohydrate modification. Here we report a concise semisynthetic strategy to access diverse 2- and 4-deoxygenated carbohydrates without relying on the exhaustive use of protecting groups to achieve site-selective reaction outcomes.

Selective Transformations of Carbohydrates Inspired by Radical-Based Enzymatic Mechanisms.

Enzymes are a longstanding source of inspiration for synthetic reaction development. However, enzymatic reactivity and selectivity are frequently untenable in a synthetic context, as the principles that govern control in an enzymatic setting often do not translate to small molecule catalysis. Recent synthetic methods have revealed the viability of using small molecule catalysts to promote highly selective radical-mediated transformations of minimally protected sugar substrates.

Synthesis of rare sugar isomers through site-selective epimerization.

Glycans have diverse physiological functions, ranging from energy storage and structural integrity to cell signalling and the regulation of intracellular processes. Although biomass-derived carbohydrates (such as D-glucose, D-xylose and D-galactose) are extracted on commercial scales, and serve as renewable chemical feedstocks and building blocks, there are hundreds of distinct monosaccharides that typically cannot be isolated from their natural sources and must instead be prepared through multistep chemical or enzymatic syntheses. These 'rare' sugars feature prominently in bioactive natural products and pharmaceuticals, including antiviral, antibacterial, anticancer and cardiac drugs.