Research On The Synthesis Of Vildagliptin And It's Related Substance

Diabetes is a chronic disease that caused by an absolute or relative lack of insulin which lead to glucose metabolism disorder.This disease can be divided into insulin-dependent?type 1,namely IDDM?and non insulin-dependent?type 2,namely NIDDM?.The NIDDM patients accounts for more than 90%in all the cases and the prevalence of diabetes is up to 9.7%in our country.Vildagliptin,is a dipeptidyl peptidase IV?DPP-IV?inhibitor developed by Novartis company.It is an oral hypoglycemic drug.In September 2007,Vildagliptin was approved in the EU market,clinically for the treatment of type 2 diabetes mellitus.This product decreases the inactivation level of glucagon peptide-1?GLP-1?by selectively inhibiting the DPP-IV.While prompting the amount of insulin produced by pancreatic islet cells,it also reduces the glucagon concentration.Thus it will lead to the decreasing of the blood glucose.Compared with the traditional drug,the drug was well tolerated,with low incidence of adverse reactions,without increasing the risk of hypoglycemia and no significant effect on body weight.The synthesis process of Vildagliptin was improved by consulting relevant paper.By using L-proline as starting material,through BOC protection,amidation,dehydration,deprotection and salt forming,chloride acetylation to get S-1-?2-chloroacetyl?-2-cyano pyrrolidine?intermediate-5?,which was subjected to condensation with3-amino-1-adamantanol to obtain the target product of Vildagliptin.The structure of the target compound was confirmed by nuclear magnetic resonance(¹H-NMR and ¹³C-NMR),mass spectrometry and infrared spectroscopy,and the total yield was 26%.In addition,Vildagliptin related substances were synthesized in order to meet the requirements of the quality control of raw material and formulation,and the structures of these related substances were confirmed by nuclear magnetic resonance(¹H-NMR and ¹³C-NMR).