Development of a Concise, Asymmetric Synthesis of a Smoothened Receptor (SMO) inhibitor: Enzymatic Transamination of a 4-Piperidinone with Dynamic Kinetic Resolution

A concise, asymmetric synthesis of a smoothened receptor inhibitor (1) is described. The synthesis features an enzymatic transamination with concurrent dynamic kinetic resolution (DKR) of a 4-piperidone (4). to establish the two stereogenic centers required in a single step. This efficient reaction affords the desired anti amine (3) in >10:1 dr and >99% ee. The title compound is prepared in only five steps with 40% overall yield.