Development of a concise, asymmetric synthesis of a smoothened receptor (SMO) inhibitor: enzymatic transamination of a 4-piperidinone with dynamic kinetic resolution.
Development of a concise, asymmetric synthesis of a smoothened receptor (SMO) inhibitor: enzymatic transamination of a 4-piperidinone with dynamic kinetic resolution.
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DOI：
10.1021/ol403630g
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发表时间：
2014-01
期刊：
影响因子：
5.2
通讯作者：
Zhihui Peng;J. W. Wong;E. Hansen;Angela L. A. Puchlopek-Dermenci;Hugh J. Clarke
中科院分区：
文献类型：
--
作者：
Zhihui Peng;J. W. Wong;E. Hansen;Angela L. A. Puchlopek-Dermenci;Hugh J. Clarke
描述了一种smoothened受体抑制剂（1）的简洁、不对称合成。该合成的特征在于酶促转氨作用与4-哌啶酮（4）的同时动态动力学拆分（DKR），以在单个步骤中建立所需的两个立体中心。此反应效率高，可得到所需的反胺（3），其dr>10：1，ee>99%，标题化合物仅经五步反应制得，总收率40%。
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.