title: Development of a concise, asymmetric synthesis of a smoothened receptor (SMO) inhibitor: enzymatic transamination of a 4-piperidinone with dynamic kinetic resolution.
abstract: 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.
authors: Chemical Research & Development, ‡Analytical Research & Development, Pfizer Worldwide Research & Development , Eastern Point Road, Groton, Connecticut 06340, United States.
authors: Zhihui
authors: Z
authors: Peng
authors: John W
authors: JW
authors: Wong
authors: Eric C
authors: EC
authors: Hansen
authors: Angela L A
authors: AL
authors: Puchlopek-Dermenci
authors: Hugh J
authors: HJ
authors: Clarke
mesh_terms: D002384:Catalysis; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D010881:Piperidones / Q000138:chemical synthesis* / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D010881:Piperidones; D043562:Receptors, G-Protein-Coupled