Enantioselective Synthesis of (-)-Acetylapoaranotin.

The first enantioselective total synthesis of the epipolythiodiketopiperazine (ETP) natural product (-)-acetylapoaranotin (3) is reported. The concise synthesis was enabled by an eight-step synthesis of a key cyclohexadienol-containing amino ester building block. The absolute stereochemistry of both amino ester building blocks used in the synthesis is set through catalytic asymmetric (1,3)-dipolar cycloaddition reactions. The formal syntheses of (-)-emethallicin E and (-)-haemotocin are also achieved through the preparation of a symmetric cyclohexadienol-containing diketopiperazine.

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.