Synthesis of Vildagliptin-β- O -Glucuronide

Abstract

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-gly-cosylation 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.