COMPETITORS WANT TO GET A PIECE OF LIPITOR: Biocatalysis offers a variety of enantioselective routes to key chiral intermediates for the drug

A TORVASTATIN, THE ACTIVE ingredient in Pfizer's cholesterol-lowering drug Lipitor, has a (3R,5S)-dihydroxyhexanoate side chain that accounts for about 25% of the compound's molecular weight. On a prorated basis, that would make the side chain worth roughly $3 billion, since sales of Pfizer's lipitor exceed $12 billion per year. Fine chemicals producers are actually making much less money on intermediates used to construct that side chain, but they are still competing with routes to supply the 220-ton-per-year market for these building blocks. Several "statin" drugs incorporate related 3,5-dihydroxyacid side chains, and about half come from microbial sources; those of Lipitor and AstraZeneca's Crestor (rosuvastatin), on the other hand, are synthesized. Making the side chain is challenging because it has two chiral centers, and greater than 99.5% enantiomeric and 99% diastereomeric excess are required. Biocatalysis has emerged as a versatile tool for achieving this and avoiding problems with traditional ch...