Synthesis of Atorvastatin
The development of synthetic routes to atorvastatin, probably the most commercially successful small molecule drug ever launched, has spanned some 25 years. The changing requirements of synthetic routes and the reagents encompassed by these have paralleled the life-cycle of the drug. These requirements have shifted from flexibility, reliability and speed in the medicinal chemistry phase to suitability for scale-up and overall yield in the development phase. Emphasis on routes that exhibit low cost and reduced environmental impact has come to the forefront in manufacturing. The desire for increasingly efficient and low-hazard chemistry in the development and manufacture of this drug has been both accompanied by and provided a stimulus to the rise of asymmetric catalysis, especially biocatalysis. The implementation of asymmetric catalysis, and its integration into the overall route alongside other improvements has had a major impact in increased efficiency and minimisation of hazards in production of this drug.