Asymmetric total synthesis of Tofacitinib

作者：Marican Adolfo; Simirgiotis Mario J; Santos Leonardo S^*

来源：Tetrahedron Letters, 2013, 54(37): 5096-5098.

DOI：10.1016/j.tetlet.2013.07.042

• CP-690,550
• JAK3 inhibitor
• Mitsunobu reaction
• Alane reduction

A novel stereoselective synthesis of Tofacitinib (CP-690,550), a Janus tyrosine kinase (JAK3) specific inhibitor, has been achieved starting from (5S)-5-hydroxypiperidin-2-one in 10 steps from 2 with a 9.5% overall yield. The potentiality of this synthetic route is the obtention of tert-butyl-(3S,4R)-3-hydroxy-4-methylpiperidine-1-carboxylate (6b) as a new chiral precursor involved in the synthesis of CP690,550, in a three-step reaction, without epimerizations, rather than the 5 or more steps used in described reactions to achieve this compound from analogues of 6b.

• 出版日期2013-9-11