The Synthesis And Analyzes Of Chiral Medicine Salmeterol

Salmeterol is an ideal long acting and good selecting medicine which was developed by GSK Corporation. It is clinically used as a long acting inhaled bronchodilator for maintenance treament of asthma and to control nocturnal asthma. In 2003 salmeterol was one of the global best-selling medicines. Till now this drug is marketed as a racemate. However the enantinmers of salmerterol are different. (R)-enantiomer is more active forβ-agonists and it have less side effects compared to its racemate. However, Sepracor also claimed that the (S)-enantiomer of salmeterol had a higher selectivity forβ₂-receptors. Single enantiomers have reduced side effects compared to their racements. It is meaningful to find out a simple and convenient route for the synthesis of the single enantiomers of salmeterol.As part of our research program, we are interested in developing a simple and efficient rounte for the synthesis of salmeterol and its analogs. Meanwhile we used different kinds of analytical methods to analyze various intermediates.The key step in synthsis is asymmetric synthsis of the chrial intermediate. In this experiment we designed and synthesized a new ligand S,S-DiMeTsDPEN Which catalyzed asymmetric transfer hydrogenation of ketones. A new ligand of S,S-DiMeTsDPEN, which catalyzed asymmetric transfer hydrogenation of ketones, was designed and synthesized in this dissertation. The prepared ligand behaved well in asymmetric transfer hydrogenation of ketones. When HCOONa was taken as the hydrogen donor, both Rh- and Ru-TsDPEN catalyzed asymmetric transfer hydrogenation ofα-bromoketone intermediate in water gave a desired productα-bromoalcohol intermediate with good yield.For a racemic compound, physical and chemical propeties of enantiomers are similar, so that the traditional analysis methods are difficulty to separatethem. In the dissertation it was tried to find out a method of chiral resolution and successfully to separate the chiral ligand. Then different kinds of methods to identify the optical purity of the enantiomer.The experiment demonstrated that the new chiral ligand had well performance in asymmetric transfer hydrogenation, the optical purity of each chiral intermediate reached to 85% ee values .