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