Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide

• 作者: Mahavir Prashad Wen-Chung Shieh Yansong Jack Lu Yugang Liu
• 来源期刊: 化学工程与科学期刊(英文)
• 学科: 化学
• 关键词: VILDAGLIPTIN O-GLYCOSYLATION DPP-4 Inhibitors Type-2 Diabetes
• 年，卷（期）: 2012,（3）
• 页码范围: 379-383
• 页数: 5页
• 分类号: O6

摘要

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.