There is a global effort to convert sunlight into fuels by photoelectrochemically splitting water to form hydrogen fuels, but the dioxygen byproduct bears little economic value. This raises the important question of whether higher value commodities can be produced instead of dioxygen. We report here photoelectrochemistry at a BiVO4 photoanode involving the oxidation of substrates in organic media. The use of MeCN instead of water enables a broader set of chemical transformations to be performed (e.g., alcohol oxidation and C-H activation/oxidation), while suppressing photocorrosion of BiVO4 that otherwise occurs readily in water, and sunlight reduces the electrical energy required to drive organic transformations by 60%. These collective results demonstrate the utility of using photoelectrochemical cells to mediate organic transformations that otherwise require expensive and toxic reagents or catalysts.
Unprotected aziridine aldehydes belong to the amphoteric class of molecules by virtue of their dual nucleophilicity/electrophilicity. The dimeric nature of these molecules, brought together by a weak and reversible aminal "connection", was found to be an important element of reactivity control. We present evidence that reversible dimer dissociation is instrumental in aziridine aldehyde transformations. We anticipate further developments that will unveil other synthetic consequences of remote control of selectivity through forging reversible covalent interactions.
Diaryliodonium triflates transfer an aryl group to the chalcogen atom of organic sulfides, selenides, and tellurides (but not ethers), in the absence of transition-metal catalyst, simply upon heating in chloroform or dichloroethane solution.
Inhibition of glucosylceramide
synthase (GCS) is a major therapeutic
strategy for Gaucher’s disease and has been suggested as a
potential target for treating Parkinson’s disease. Herein,
we report the discovery of novel brain-penetrant GCS inhibitors. Assessment
of the structure–activity relationship revealed a unique pharmacophore
in this series. The lipophilic ortho-substituent of aromatic ring
A and the appropriate directionality of aromatic ring B were key for
potency. Optimization of the absorption, distribution, metabolism,
elimination, toxicity (ADMETox) profile resulted in the discovery
of T-036, a potent GCS inhibitor in vivo. Pharmacophore-based
scaffold hopping was performed to mitigate safety concerns associated
with T-036. The ring opening of T-036 resulted
in another potent GCS inhibitor with a lower toxicological risk, T-690, which reduced glucosylceramide in a dose-dependent
manner in the plasma and cortex of mice. Finally, we discuss the structural
aspects of the compounds that impart a unique inhibition mode and
lower the cardiovascular risk.
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