Resolving Inflammation: Synthesis,Configurational Assignment,and Biological Evaluations of RvD1n−3 DPA

New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro-resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro-resolving mediator RvD1_{n−3 DPA} has been achieved using the underutilized sp³–sp³ Negishi cross coupling reaction and an alkyne hydrosilylation–protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.     

Reactions of Verbenone Dienolate with Aromatic Aldehydes

Lithium dienolate of verbenone reacts with aromatic aldehydes to give α- and γ-aldols. Unusual features of the reaction include: selective formation of the γ-aldols under kinetic conditions, absence of deconjugated α-products, high sensitivity to electronic effects and formation of bis-aldols 5.     

The Protection of Terminal Alkynes Against Grignard Reagents by the Trimethylsilyl Group

Representative alkynyltrimethylsilyl groups were found to be inert to Grignard reagents.     

One-pot synthesis of meridianins and meridianin analogues via indolization of nitrosoarenes

Meridianins, marine alkaloids known as kinase inhibitors with an indole skeleton, and meridianin analogues were produced regioselectively and in moderate to good yields by thermal annulation of nitrosoarenes with 2-amino-4-ethynylpyrimidine and 2-chloro-4-ethynylpyrimidine, respectively, through a novel and atom-economical indolization process.