Electrochemical Dehydrogenative C(sp2 )-H Amination.

A transition-metal-free direct electrolytic C-H amination involving an electrochemically generated nitrenium ion intermediate has been developed. The electrosynthesis takes place in the absence of any organoiodine catalysts and is enabled by an in situ generated electrolyte. A novel, efficient intramolecular and intermolecular C-H amination has been demonstrated using a simple reaction setup.

Probing Embryonic Development Enables the Discovery of Unique Small-Molecule Bone Morphogenetic Protein Potentiators.

We report on the feasibility to harness embryonic development in vitro for the identification of small-molecule cytokine mimetics and signaling activators. Here, a phenotypic, target-agnostic, high-throughput assay is presented that probes bone morphogenetic protein (BMP) signaling during mesodermal patterning of embryonic stem cells. The temporal discrimination of BMP- and transforming growth factor-ß (TGFß)-driven stages of cardiomyogenesis underpins a selective, authentic orchestration of BMP cues that can be recapitulated for the discovery of BMP activator chemotypes. Proof of concept is shown from a chemical screen of 7000 compounds, provides a robust hit validation workflow, and afforded 2,3-disubstituted 4H-chromen-4-ones as potent BMP potentiators with osteogenic efficacy. Mechanistic studies suggest that Chromenone 1 enhances canonical BMP outputs at the expense of TGFß-Smads in an unprecedented manner. Pharmacophoric features were defined, providing a set of novel chemical probes for various applications in (stem) cell biology, regenerative medicine, and basic research on the BMP pathway.

Catalytic Selective Metal-Free Cross-Coupling of Heteroaromatic N-Oxides with Organosilanes.

A metal-free, regioselective C-H functionalization of heteroaromatic N-oxides has been developed. The method enables the synthesis of various benzylated and alkynylated N-heterocycles in a transition-metal-free manner employing organosilanes as coupling partners. The unanticipated reactivity has been exploited for the synthesis of a number of symmetrical disubstituted acetylenes from ethynyltrimethylsilane via carbon-silicon bond metathesis.