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 a...

Full description

Saved in:
Bibliographic Details
Published in:Organic letters 2014-02, Vol.16 (3), p.860-863
Main Authors: Peng, Zhihui, Wong, John W, Hansen, Eric C, Puchlopek-Dermenci, Angela L. A, Clarke, Hugh J
Format: Article
Language:English
Subjects:
Catalysis
Humans
Kinetics
Molecular Structure
Piperidones - chemical synthesis
Piperidones - chemistry
Receptors, G-Protein-Coupled - antagonists & inhibitors
Receptors, G-Protein-Coupled - chemistry
Stereoisomerism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol403630g