Formal asymmetric synthesis of (+)-tofacitinib |
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Authors: | Hao-Chun Liao Biing-Jiun Uang |
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Institution: | Department of Chemistry, National Tsing Hua University, No. 101, Sec 2, Kuang-Fu Rd., Hsinchu City 30013, Taiwan |
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Abstract: | 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. |
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Keywords: | Corresponding author Tel : +886 3 5715131 33410 fax: +886 3 5711082 |
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