Oxidative Dearomatization of Indoles via Pd-Catalyzed C–H Oxygenation: An Entry to C2-Quaternary Indolin-3-ones

An oxidative dearomatization chemistry of 2-arylindole via a unique pathway involving Pd-catalyzed C–H peroxygenation is documented. Coupled with cascade transformation, it provides a new route to access indolin-3-ones bearing a C2-quaternary functionality, including a chiral center (indoxyls), a motif prevalent in indole alkaloids but synthetically underexplored. The method is chemo- and regioselective and compatible with versatile substrates. A mechanism has been outlined on the basis of results of control experiments, isolation/use of intermediates, and spectroscopic studies

Novel Combretastatin-2-aminoimidazole Analogues as Potent Tubulin Assembly Inhibitors: Exploration of Unique Pharmacophoric Impact of Bridging Skeleton and Aryl Moiety

Combretastatin A-4 (CA-4) in phosphate and serine pro-drug forms is under phase II clinical trials. With our interest of discovering CA-4 inspired new chemical entities, a novel series of 4,5-diaryl-2-aminoimidazole analogues of the compound was designed and synthesized by an efficient and diversity feasible route involving atom economical arene C–H bond arylation. Interestingly, four compounds showed potent cell-based antiproliferative activities in nanomolar concentrations. Among the compounds, compound <b>12</b> inhibited the proliferation of several types of cancer cells much more efficiently than CA-4. It depolymerized microtubules, induced spindle defects, and stalled mitosis in cells. Compound <b>12</b> bound to tubulin and inhibited the polymerization of tubulin in vitro. In addition, podophyllotoxin and CA-4 inhibited the binding of compound <b>12</b> to tubulin. The distinctive pharmacophoric features of the bridging motif as well as quinoline nucleus were explored. We noted also a valuable quality of compound <b>12</b> as a potential probe in characterizing new CA-4 analogues

Synthesis of Polyfunctionalized Pyrroles via a Tandem Reaction of Michael Addition and Intramolecular Cyanide-Mediated Nitrile-to-Nitrile Condensation

A new approach for the synthesis of tetrasubstituted/functionalized NH-pyrroles from <i>gem</i>-diactivated acrylonitriles and TMSCN has been developed. The strategy utilizes the generation of <i>vic</i>-dinitrile via Michael addition and cyanide-mediated nitrile-to-nitrile cyclocondensation, which proceed in tandem guided by manifold roles of “CN”. An extended application to the production of fused pyrrole has also been realized

Synthesis of Polyfunctionalized Pyrroles via a Tandem Reaction of Michael Addition and Intramolecular Cyanide-Mediated Nitrile-to-Nitrile Condensation

A new approach for the synthesis of tetrasubstituted/functionalized NH-pyrroles from <i>gem</i>-diactivated acrylonitriles and TMSCN has been developed. The strategy utilizes the generation of <i>vic</i>-dinitrile via Michael addition and cyanide-mediated nitrile-to-nitrile cyclocondensation, which proceed in tandem guided by manifold roles of “CN”. An extended application to the production of fused pyrrole has also been realized