Synthesis of Vildagliptin-β-O-Glucuronide


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.

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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.

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The authors declare no conflicts of interest.


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