We report a general protocol for the light-driven isomerization of cyclic aliphatic alcohols to linear carbonyl compounds. These reactions proceed via proton-coupled electron transfer (PCET) activation of alcohol O-H bonds followed by subsequent CC β-scission of the resulting alkoxy radical intermediates. In many cases, these redox-neutral isomerizations proceed in opposition to a significant energetic gradient, yielding products that are less thermodynamically stable than the starting materials. A mechanism is presented to rationalize this out-of-equilibrium behavior that may serve as a model for the design of other contrathermodynamic transformations driven by excited-state redox events.

Photoaffinity labeling (PAL) is an important tool in chemical biology research, but application of α-ketoamides for PAL has been hampered by their photoinstability. Here, we show that 2-thienyl-substituted α-ketoamide is a superior photoreactive group for PAL. Studies with a series of synthetic mannose-conjugated α-ketoamides revealed that 2-thienyl substitution of α-ketoamide decreased the electrophilicity of the keto group and reduced the rate of photodegradation. Mannose-conjugated thienyl α-ketoamide showed greater concanavalin A labeling efficiency than other alkyl or phenyl-substituted α-ketoamides. In comparison with representative conventional photoreactive groups, 2-thienyl ketoamide showed reduced labeling of nontarget proteins, probably owing to its lower hydrophobicity.

No abstract

Glycoconjugates are an important class of biomolecules that regulate numerous biological events in cells. However, these complex, medium-size molecules are metabolically unstable, which hampers detailed investigations of their functions as well as their potential application as pharmaceuticals. Here we report sialidase-resistant analogues of ganglioside GM3 containing a monofluoromethylene linkage instead of the native O -sialoside linkage. Stereoselective synthesis of CHF -linked disaccharides and kinetically controlled Au(I)-catalyzed glycosylation efficiently furnished both stereoisomers of CHF -linked as well as CF 2 - and CH 2 -linked GM3 analogues. Like native GM3, the C -linked GM3 analogues inhibited the autophosphorylation of epidermal growth factor (EGF) receptor induced by EGF in vitro . Assay of the proliferation-enhancing activity toward Had-1 cells together with NMR-based conformational analysis showed that the ( S )- CHF -linked GM3 analogue with exo -gauche conformation is the most potent of the synthesized compounds. Our findings suggest that exo -anomeric conformation is important for the biological functions of GM3.