Density functional theory was used to calculate C− H bond dissociation enthalpies (BDEs) at each position of a diverse collection of pyranosides and furanosides differing in relative configuration and substitution patterns. A detailed analysis of the resulting data set (186 BDEs, calculated at the M06-2X/ def2-TZVP level of theory) highlights the ways in which stereoelectronic effects, conformational properties, and noncovalent interactions can influence the strengths of C−H bonds in carbohydrates. The results point toward opportunities to alter the radical reactivity of carbohydrate derivatives by variation of their stereochemical configuration or the positions and types of protective groups.

The combined action of a photoredox catalyst, a hydrogen atom transfer mediator, and a hydrogen bond acceptor cocatalyst has been used to achieve the transformation of pyranoside-derived esters into ketodeoxysugars. The position of the acyl group dictates the site of deoxygenation, enabling the preparation of 2-deoxy-and 4-deoxyketosugar derivatives. The products are useful precursors to rare sugar components of bioactive secondary metabolites. Computational studies are consistent with a radical lyaselike mechanism wherein the key elimination step proceeds via 1,2-acyloxy migration in the radical intermediate.

Diorganotin dihalides act as cocatalysts for site-selective and stereoselective couplings of diol-containing carbohydrates with electron-deficient alkenes in the presence of an Ir­(III) photoredox catalyst and quinuclidine, a hydrogen atom transfer mediator. Quantum-chemical calculations support a proposed mechanism involving the formation of a cyclic stannylene acetal intermediate that shows enhanced reactivity toward hydrogen atom abstraction by the quinuclidinium radical cation. Addition of the carbon-centered radical to the alkene partner results in C-alkylation of the carbohydrate substrate.

Traumatic brain injury (TBI) survivors suffer long term from mental illness, neurodegeneration, and neuroinflammation. Studies of 3D tissue models have provided new insights into the pathobiology of many brain diseases. Here, a 3D in vitro contusion model is developed consisting of mouse cortical neurons grown on a silk scaffold embedded in collagen and used outcomes from an in vivo model for benchmarking. Molecular, cellular, and network events are characterized in response to controlled cortical impact (CCI). In this model, CCI induces degradation of neural network structure and function and release of glutamate, which are associated with the expression of programmed necrosis marker phosphorylated Mixed Lineage Kinase Domain Like Pseudokinase (pMLKL). Neurodegeneration is observed first in the directly impacted area and it subsequently spreads over time in 3D space. CCI reduces phosphorylated protein kinase B (pAKT) and Glycogen synthase kinase 3 beta (GSK3β) in neurons in vitro and in vivo, but discordant responses are observed in phosphprylated ribosomal S6 kinase (pS6) and phosphorylated Tau (pTau) expression. In summary, the 3D brain‐like culture system mimicked many aspects of in vivo responses to CCI, providing evidence that the model can be used to study the molecular, cellular, and functional sequelae of TBI, opening up new possibilities for discovery of therapeutics.

Methods for site-selective sulfamoylation of secondary hydroxyl groups in pyranosides are described. Using a boronic acid catalyst, selective installation of a Boc-protected sulfamoyl group at the equatorial position of cis-diols in manno-and galactoconfigured substrates has been achieved. Activation of trans-diol groups in gluco-and galacto-configured substrates is also possible by employing an organotin catalyst.