Formal asymmetric synthesis of (+)-tofacitinib

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• 作者：Hao-Chun Liao ; Biing-Jiun Uang ; ^{bjuang@mx.nthu.edu.tw}
• 刊名：Tetrahedron: Asymmetry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：28
• 期：1
• 页码：105-109
• 全文大小：741 K
• 卷排序：28

文摘

Tofacitinib is an efficient and selective Janus kinase 3 (JAK3) inhibitor, and is used as an immunosuppressant drug for the treatment of rheumatoid arthritis and transplant patients. Herein we report a concise formal asymmetric synthesis of tofacitinib from homochiral 1,3-dioxolanone 10b, which was elaborated through a highly stereoselective Michael addition followed by solvent-free removal of the chiral auxiliary and ring cyclization to furnish chiral imide 8. The preparation of tofacitinib’s precursor 16 could be obtained after reduction of 8 followed by sequential oxidation, reductive amination and SNAr reactions.