No abstract

The first asymmetric insertion reactions of donor–donor carbenoids, i.e., those with no pendant electron-withdrawing groups, are reported. This process enables the synthesis of densely substituted benzodihydrofurans with high levels of enantio- and diastereoselectivity. Preliminary results show similar efficiency in the preparation of indanes. This new method is used in the first enantioselective synthesis of an oligoresveratrol natural product (E-δ-viniferin).

Easy does it: Easily handled and environmentally safe oxone generates singlet oxygen which effects the simple and selective oxidative de‐aromatization of para‐alkyl phenols 1 into para‐peroxyquinols 2 under very mild conditions with good to excellent yields. A one‐pot access to para‐quinols 3 from 1 is also possible after treatment of the crude reaction mixture with sodium thiosulfate.

No abstract

Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) is a promising anti-cancer agent because it shows apoptosis-inducing activity in transformed, but not in normal cells. As with most anti-cancer agents, however, its clinical use is restricted by either inherent or acquired resistance by cancer cells. We demonstrate here that small-molecule SMAC mimetics that antagonize the Inhibitor of Apoptosis Proteins (IAPs) potently sensitize previously resistant human cancer cell lines, but not normal cells, to TRAIL-induced apoptosis, and that they do so in a caspase-8-dependent manner. We further show that the compounds have no cytotoxicity as single agents. Also, we demonstrate that several IAP family members likely participate in the modulation of cellular sensitivity to TRAIL. Finally, we note that the compounds that sensitize cancer cells to TRAIL are the most efficacious in binding to XIAP, and in inducing cIAP-1 and cIAP-2 degradation. Our studies thus describe valuable compounds that allow elucidation of the signaling events occurring in TRAIL resistance, and demonstrate that these agents act as potent TRAIL-sensitizing agents in a variety of cancer cell lines.