https://www.selleckchem.com/products/cb-839.html We developed a green method for the synthesis of spiro[4.5]trienones through an electrochemical oxidative halocyclization with N-aryl alkynamides. This reaction was conducted under metal-catalyst- and exogenous-oxidant-free conditions at room temperature. Using readily available LiCl, LiBr, and LiI as the halogen source, a variety of dearomative halo-spirocyclization products were obtained in good to excellent yields with a broad scope and functional group tolerance.Previously, we reported a first-in-class von Hippel-Lindau (VHL)-recruiting mitogen-activated protein kinase kinases 1 and 2 (MEK1/2) degrader, MS432. To date, only two MEK1/2 degrader papers have been published and very limited structure-activity relationships (SAR) have been reported. Here, we describe our extensive SAR studies exploring both von Hippel-Lindau (VHL) and cereblon (CRBN) E3 ligase ligands and a variety of linkers, which resulted in two novel, improved VHL-recruiting MEK1/2 degraders, 24 (MS928) and 27 (MS934), and the first CRBN-recruiting MEK1/2 degrader 50 (MS910). These compounds potently and selectively degraded MEK1/2 by hijacking the ubiquitin-proteasome system, inhibited downstream signaling, and suppressed cancer cell proliferation. Furthermore, concurrent inhibition of BRAF or PI3K significantly potentiated the antitumor activity of degrader 27, suggesting that the combination of MEK1/2 degradation with BRAF or PI3K inhibition may provide potential therapeutic benefits. Finally, besides being more potent, degrader 27 displayed improved plasma exposure levels in mice, representing the best MEK1/2 degrader to date for in vivo studies.Resistance switching properties of nanoscale junctions of spin crossover molecules have received recently much interest. In many cases, this property has been traced back to the variation of molecular orbital energies upon spin transition. However, one can also expect a substantial reorganization of the