A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin

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• 作者：Sung Kwon Kang^a ; ^b ; Gyeong Hi Cho^b ; Hyung Joon Leem^b ; Bong Kwan Soh^b ; Jaehoon Sim^a ; Young-Ger Suh^a ;
• 刊名：Tetrahedron: Asymmetry
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：28
• 期：1
• 页码：34-40
• 全文大小：1182 K
• 卷排序：28

文摘

A highly stereoselective and efficient synthesis of sitagliptin 1 consisting of a chiral β-amino acid unit has been achieved through 6 steps from commercially available 2,4,5-trifluorobenzaldehyde 4. The chiral antidiabetic drug was obtained with almost perfect enantiomeric purity (>99.9% ee) in 40.9% overall yield. The key feature of the synthesis is the addition of a malonate enolate to a chiral sulfinylimine in more than 99:1 dr. Our synthetic procedure proved to be highly efficient, economical, and sustainable.