page_title: Atorvastatin
section_title: Chemical synthesis
hierarchical_section_title: Atorvastatin / Society and culture / Chemical synthesis
caption_attribution_description: English: Atorvastatin synthesis in commercial production (process) chemistry. The key step establishing a stereocenter in this apparent commercial route to atorvastatin makes use of a readily available natural product, isoascornic acid, thus following a chiral pool approach to set the stereochemistry of the first alcohol functional group. Associated REF "Chapter 9. Atorvastatin Calcium (Lipitor)" in (2004) Contemporary Drug Synthesis, John Wiley &amp; Sons, Inc., pp.&#160;113–125 ISBN&#58; 0-471-21480-9.&#32;. Created by dividing/cropping original image File:Atorvastatin_routes.png of User:Jammercer. NOTE: Integrity of information contained in the image is judged reasonable by this expert, but this citation was not actually contained in the source file, and image details were not checked against this inferred source. Use source and image only with verification of content for each intended purpose. Le Prof
context_page_description: Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.
  Common side effects include joint pain, diarrhea, heartburn, nausea, and muscle pains. Serious side effects may include rhabdomyolysis, liver problems, and diabetes. Use during pregnancy may harm the baby. Like all statins, atorvastatin works by inhibiting HMG-CoA reductase, an enzyme found in the liver that plays a role in producing cholesterol.
  Atorvastatin was patented in 1986, and approved for medical use in the United States in 1996. It is available as a generic medication and is relatively inexpensive. In 2017, it was the second most prescribed medication in the United States, with more than 104 million prescriptions.
context_section_description: The first synthesis of atorvastatin at Parke-Davis that occurred during drug discovery was racemic followed by chiral chromatographic separation of the enantiomers. An early enantioselective route to atorvastatin made use of an ester chiral auxiliary to set the stereochemistry of the first of the two alcohol functional groups via a diastereoselective aldol reaction.
  Once the compound entered pre-clinical development, process chemistry developed a cost-effective and scalable synthesis. In atorvastatin's case, a key element of the overall synthesis was ensuring stereochemical purity in the final drug substance, and hence establishing the first stereocenter became a key aspect of the overall design. The final commercial production of atorvastatin relied on a chiral pool approach, where the stereochemistry of the first alcohol functional group was carried into the synthesis—through the choice of isoascorbic acid, an inexpensive and easily sourced plant-derived natural product.
caption: Atorvastatin synthesis in commercial production (process) chemistry. The key step of establishing this medication's stereocenters, through initial use of an inexpensive natural product (chiral pool approach).
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