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Synthesis of Vildagliptin-β-<i>O</i>-Glucuronide
Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
- 1 Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
- 2 Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
- 3 Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
- 4 Chemical and Analytical Development, Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, USA
Advances in Chemical Engineering and Science·Volume 02 (2012)·Pages 379–383·Published 24 July 2012·DOI10.4236/aces.2012.23045
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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 -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.
KeywordsVildagliptin<i>O</i>-GlycosylationDPP-4 InhibitorsType-2 Diabetes
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