Interleukin-11 receptor is an alternative α-receptor for interleukin-6 and the chimeric cytokine IC7.

The cytokine interleukin 6 (IL-6) signals via the IL-6 α-receptor (IL-6Rα or IL-6R) in complex with the gp130 β-receptor. Cell type restricted expression of the IL-6R limits the action of IL-6 mainly to hepatocytes and some immune cells. Here, we show that IL-6 also binds to the IL-11 α receptor (IL-11Rα or IL-11R) and induces signaling via IL-11R:gp130 complexes, albeit with a lower affinity compared to IL-11.

α-Amino bicycloalkylation through organophotoredox catalysis.

Bridged bicycloalkanes such as bicyclo[1.1.1]pentanes (BCPs) and bicyclo[3.

Taming nonclassical carbocations to control small ring reactivity.

Prediction of the outcome of ring opening of small organic rings under cationic conditions can be challenging due to the intermediacy of nonclassical carbocations. For example, the solvolysis of cyclobutyl or cyclopropylmethyl derivatives generates up to four products on nucleophilic capture or elimination via cyclopropylcarbinyl and bicyclobutonium ions. Here, we show that such reaction outcomes can be controlled by subtle changes to the structure of nonclassical carbocation.

Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane.

Small-ring cage hydrocarbons are popular bioisosteres (molecular replacements) for commonly found para-substituted benzene rings in drug design. The utility of these cage structures derives from their superior pharmacokinetic properties compared with their parent aromatics, including improved solubility and reduced susceptibility to metabolism. A prime example is the bicyclo[1.

Collective Synthesis of Illudalane Sesquiterpenes via Cascade Inverse Electron Demand (4 + 2) Cycloadditions of Thiophene ,-Dioxides.

Thiophene dioxides are underutilized tools for the construction of benzene rings in organic synthesis. We report a collective synthesis of nine illudalane sesquiterpenes using bicyclic thiophene dioxides as generalized precursors to the indane core of the natural products. Exploiting furans as unusual dienophiles in this inverse electron demand Diels-Alder cascade, this concise and convergent approach enables the synthesis of these targets in as little as five steps.

Synthesis of α-Quaternary Bicyclo[1.1.1]pentanes through Synergistic Organophotoredox and Hydrogen Atom Transfer Catalysis.

Bicyclo[1.1.1]pentanes (BCPs) are important in drug design as sp-rich bioisosteres of arenes and -butyl groups; however, the preparation of BCPs with adjacent quaternary carbons is barely known.

-Substitutions at Five-Membered Hetarenes Enabled by Sulfonium Salts.

We report a nucleophilic substitution reaction of five-membered hetarylsulfonium salts that results in a change of the substitution pattern on the arene. The products of these -substitutions are hard to access synthetically otherwise. The sulfonium salts that serve as starting materials are generated by a highly site-selective C-H functionalization reaction.

Site-selective and versatile aromatic C-H functionalization by thianthrenation.

Direct C-H functionalization can quickly increase useful structural and functional molecular complexity. Site selectivity can sometimes be achieved through appropriate directing groups or substitution patterns-in the absence of such functionality, most aromatic C-H functionalization reactions provide more than one product isomer for most substrates. Development of a C-H functionalization reaction that proceeds with high positional selectivity and installs a functional group that can serve as a synthetic linchpin for further functionalization would provide access to a large variety of well-defined arene derivatives.

Split Protein-Ligation Generates Active IL-6-Type Hyper-Cytokines from Inactive Precursors.

Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses.