Defining Target Engagement Required for Efficacy at the Retinoic Acid Receptor-Related Orphan Receptor C2 (RORγt).

The Th17 pathway has been implicated in autoimmune diseases. The retinoic acid receptor-related orphan receptor C2 (RORγt) is a master regulator of Th17 cells and controls the expression of IL-17A. RORγt is expressed primarily in IL-17A-producing lymphoid cells.

Dual vicinal functionalisation of heterocycles an interrupted Pummerer coupling/[3,3]-sigmatropic rearrangement cascade.

A dual vicinal functionalisation cascade involving the union of heterocycles and allyl sulfoxides is described. In particular, the approach provides efficient one-step access to biologically relevant and synthetically important C3 thio, C2 carbo substituted indoles. The reaction operates under mild, metal free conditions and without directing groups, an interrupted Pummerer coupling of activated allyl sulfoxides, generating allyl heteroaryl sulfonium salts that are predisposed to a charge accelerated [3,3]-sigmatropic rearrangement.