Author(s)

Yansong Jack Lu, Yugang Liu, Mahavir Prashad, Wen-Chung Shieh

Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA.

A linear 7-step synthesis of vildagliptin-β-O-glucuronide (2) starting from commercially available D-glucurono-6, 3-lactone (3) was herein achieved with 11.3% overall yield. Efficient preparation of compound 6 in pure α form was obtained, which was proved critical to achieve high anomeric selectivity in β-O-glycosylation later. The direct β-O-glycosylation of vildagliptin (1) containing both a tertiary alcohol and a secondary amine was studied and achieved in good yield. The deprotection step to afford product was delicately executed to avoid hydrolysis of nitrile group. The target compound 2 was obtained after purification by reversed-phase C18 chromatography.

Vildagliptin; O-Glycosylation; DPP-4 Inhibitors; Type-2 Diabetes

Y. Jack Lu, Y. Liu, M. Prashad and W. Shieh, "Synthesis of Vildagliptin-β-O-Glucuronide," Advances in Chemical Engineering and Science, Vol. 2 No. 3, 2012, pp. 379-383. doi: 10.4236/aces.2012.23045.