A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin

作者：Kang Sung Kwon; Cho Gyeong Hi; Leem Hyung Joon; Soh Bong Kwan; Sim Jaehoon; Suh Young Ger^*

来源：Tetrahedron: Asymmetry , 2017, 28(1): 34-40.

DOI：10.1016/j.tetasy.2016.10.010

A highly stereoselective and efficient synthesis of sitagliptin 1 consisting of a chiral beta-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.

• 出版日期2017-1-15