Design, Synthesis, Pharmacological Evaluation Of Small Molecular Glucokinase Activators And Preparation Of Chiral Amino Alcohols

Glucokinase（GK）, a member of the hexokinase family, is a rate-limiting enzyme thatcatalyzes the conversion of glucose to glucose-6-phosphate in liver and can enhance insulinsecretion in pancreatic β-cells. It plays a critical role in whole-body glucose homeostasis.Therefore, Glucokinase activators（GKAs） have become a promising new therapeutictreatment for type II diabetes. A series of novel2,3-epoxypropionamide small molecularGKAs were designed, synthesized and characterized by¹H NMR and¹³C NMR.The resultsof in vitro test showed that these compounds possess certain GK activity, which are worthy offurther study.Chiral amino alcohols,as very important intermediates in organic synthesis, haveextensive applications in the fields of asymmetric synthesis, pharmaceutical chemistry, and soon. The preparation of Chiral amino alcohols, therefore, is a subject of considerable effort toorganic workers. Nine chiral amino acids were reduced into chiral amino alcohols by thesodium borohydride-boron trifluoride system, with stable optical rotation and relatively highyield. This method that need low cost has important practical value.