Noe Mark C, Hawkins Joel M, Snow Sheri L, Wolf-Gouveia Lilli
Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA.
J Org Chem. 2008 Apr 18;73(8):3295-8. doi: 10.1021/jo800080t. Epub 2008 Mar 14.
The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.
描述了(2R,3R)-3-甲基-3-羟基哌啶酸的不对称合成，它是双MMP-13/聚集蛋白聚糖酶抑制剂合成中的关键中间体。从香叶醇开始，通过七步反应制备得到标题化合物，总收率为41%。合成中的关键步骤包括建立手性中心的Sharpless不对称环氧化反应，以及闭环哌啶环的一锅法氧化烯烃裂解/还原胺化序列。
