Synthesis Of Four Deuterium Labelled Ezetimibe And Six Deuterium Labelled Bupropion Morpholinol

The major applications of the stable isotope labelled (SIL) drugs are as'analytical internal standards'and'biological internal standards'. The SIL compounds play an important role in the research of drug metabolites, drug design and structural reform. In this thesis, the synthesis of four deuterium labelled Ezetimibe and six deuterium labelled Bupropion Morpholinol was described.Ezetimibe is the first new type of azetidinone-based Cholesterol Absorption Inhibitors (CAIs). In this thesis, trans azetidinone was synthesized from imine and (S)-3-hydroxy-γ-lactone under low-temperature condition. Deuterium Labeled fluorobenzene was used to introduce four deuteriums to the molecule. Deuterium labelled ezetimibe was obtained through a series of reactions like Friedel-Crafts acylation, TMS reaction, condensation, dehydration, CBS reduction, and hydrogenation, with over 98% chemical purity and isotopic enrichment.Bupropion morpholinol is the main active metabolite of Bupropion, belongs to 2-aryl-2-morpholine alcohols, which has a good anti-depressant pharmacological activity. In this theisis, six deuterium labelled acetone was used as the starting material. Through a series of reactions like Strecker reaction, esterification and reduction etc., it gave six deuterium labelled Bupropion Morpholinol with over 98% chemical purity and isotopic enrichment.