Research On The Synthesis Of Saxagliptin’s Related Substances

Diabetes is one of the comprehensive metabolic diseases caused by the absolute or relative lack of insulin in the body,and its high incidence,great harm seriously affect the life-quality of patients.According to the estimation of International Diabetes Federation,the diabetes incidence of adults between 20 to 79 years old was 8.3%in countries in 2013,and the number of patients reached 382 million.It is estimated that the world will have nearly 592 million cases of diabetes in 2035.Diabetes is becoming one of the chronic noninfectious diseases which seriously threaten the health of human beings.Saxagliptin jointly developed by Bristol-Myers Squibb and Astra Zeneca is a potent and selective dipeptidyl peptidaseⅣinhibitor.In July 2009 it was approved listing in the United States for the treatment of type 2 diabetes by FDA.Clinical research results demonstrated it has the advantages of good hypoglycemic effect,high safety,favorable compliance etc.Therefore,Saxagliptin is a class of oral hypoglycemic agents which have broad market prospects.Related substances are impurities which are introduced from mainly starting materials,intermediates,polymers,side reaction products in the production process,as well as the degradation products generated during storage.Related substances research is one of most important research aspects which influence the quality of medicines.Its limitation directly reflects the quality of the drug.In order to meet the needs of quality control of Active Pharmaceutical Ingredient（API）and finished drug products,the study on the synthesis of Saxagliptin’s related substances was made in this thesis.Based on the literature and our thoughts,six starting materials related substances（four in starting material-1,two in starting material-2）,six intermediates’related substances and nine final products’related substances have been synthesized.The structures of all the twenty-one related substances have been confirmed by MS,IR and NMR(¹H-NMR and ¹³C-NMR).