The efficientp roduction of many medicinally or synthetically importants tarting materials suffers from wasteful or toxic precursors for the synthesis. In particular,the aromatic non-protected primary amine functionr epresents a versatile synthetic precursor,b ut its synthesis typicallyr equires toxic oxidizing agentsa nd transition metal catalysts. The twofold electrochemical aminationo fa ctivated benzene derivatives via Zincke intermediates provides an alternative sustainable strategy for the formation of new CÀNb onds of high synthetic value. As ap roof of concept, we use our approacht og enerate ab enzoxazinone scaffold that gained attentiona sastarting structurea gainst castrate-resistant prostate cancer.F urther improvement of the structure led to significantly increased cancer cell line toxicity.T hus, exploiting environmentally benign electrooxidation, we presentanew versatile and powerful method basedo nd irect CÀHa ctivation that is applicablef or example the production of medicinally relevant compounds.

Necrosis is a form of cell death that is detrimental to the affected tissue because the cell ruptures and releases its content (reactive oxygen species among others) into the extracellular space. Clusterin (CLU), a cytoprotective extracellular chaperone has been shown to be upregulated in the face of necrosis. We here show that in addition to CLU upregulation, necrotic cell lysates induce JNK/SAPK signaling, the IRE1α branch of the unfolded protein response (UPR), the MAPK/ERK1/2, and the mTOR signaling pathways and results in an enhanced proliferation of the vital surrounding cells. We name this novel response mechanism: Necrosis-induced Proliferation (NiP).

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