Novel Skeleton Transformation Reaction of α‑Pyrone Derivatives to Spirobicyclo[3.1.0]hexane Derivatives Using Dimethylsulfoxonium Methylide

By applying a skeleton transformation reaction using dimethylsulfoxonium methylide, a novel reaction was identified by which 5,6,7,8-tetrahydrocoumarin with the electron-withdrawing group at C3 was led to the spirobicyclo[3.1.0]hexane-cyclohexane derivative. Moreover, by establishing the scope of this reaction, it was confirmed that it is possible to apply this reaction to not only ring-fused α-pyrone derivatives but also alkyl-chain-substituted α-pyrone derivatives in moderate to good yields

Novel Skeleton Transformation Reaction of α‑Pyrone Derivatives to Spirobicyclo[3.1.0]hexane Derivatives Using Dimethylsulfoxonium Methylide

By applying a skeleton transformation reaction using dimethylsulfoxonium methylide, a novel reaction was identified by which 5,6,7,8-tetrahydrocoumarin with the electron-withdrawing group at C3 was led to the spirobicyclo[3.1.0]hexane-cyclohexane derivative. Moreover, by establishing the scope of this reaction, it was confirmed that it is possible to apply this reaction to not only ring-fused α-pyrone derivatives but also alkyl-chain-substituted α-pyrone derivatives in moderate to good yields

Vicenistatin induces early endosome-derived vacuole formation in mammalian cells

<p>Homotypic fusion of early endosomes is important for efficient protein trafficking and sorting. The key controller of this process is Rab5 which regulates several effectors and PtdInsPs levels, but whose mechanisms are largely unknown. Here, we report that vicenistatin, a natural product, enhanced homotypic fusion of early endosomes and induced the formation of large vacuole-like structures in mammalian cells. Unlike YM201636, another early endosome vacuolating compound, vicenistatin did not inhibit PIKfyve activity <i>in vitro</i> but activated Rab5-PAS pathway in cells. Furthermore, vicenistatin increased the membrane surface fluidity of cholesterol-containing liposomes <i>in vitro</i>, and cholesterol deprivation from the plasma membrane stimulated vicenistatin-induced vacuolation in cells. These results suggest that vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity.</p> <p>Vicenistatin is a novel compound that induces the formation of vacuole-like structures by activating Rab5-PAS pathway and increasing membrane fluidity.</p