Romania Cutting The Synthetic Statin Process Research

Rosuvastatin(ZD4522) is a new member of the 3-hydroxy-3-methylglutaryl coenzyme A(HMG-CoA)reductase inhibitor class of lipid-lowering drugs, which inhibits HMG-CoA reductase and subsequently suppresses the biosynthesis of cholesterol. It was launched into the U.S. market by AstraZeneca after it was approved by the Food and Drug Administration (FDA) on August 13, 2003. It has advantages of higher activity, less side-effect and lower tolerance camparing with other HMG-CoA reductase inhibitors.The mechanism arousing angina disease and the development of lipid lowering agents in the world were described in this thesis. The action mechanisms and the pharmokinetic of rosuvastatin were also reviewed.Based on the literatures, two major synthetic routes of rosuvastatin were summarized. By try and error, rosuvastatin was synthesized with the starting materials isobutyric acid, malonic acid and L-(-)-malic acid through twenty-one steps. Several synthetic process of rosuvastatin was studied and improved. The overall yield was ranged to 8.1%, which is 4.1% higher than that of the original literature. The structure of the target molecule was identified by IR, MS and ~1H-NMR. The structures of several synthetic intermediates were also identified by MS or ~1H-NMR.