A Biocatalytic Process to an Atorvastatin Intermediate

A two-step, three-enzyme process for the synthesis of a key intermediate of atorvastatin, the active ingredient in Lipitor®, has recently been reported by scientists at Codexis in conjunction with Roger Sheldon at University of Delft, Netherlands (Ma S K et al, Green Chemistry, 2010, 12, 81-86).  Attendees at Scientific Update events will have probably seen Codexis scientists discussing this work, and, although the work has been patented, this new publication gives some of the details of the attractive, and efficient process, though not as many details of scale up as presented by Jim Lalonde at the recent conferences.  Nevertheless, this paper shows how a low cost raw material can be efficiently converted into a more complex chiral nitrile, and how the efficiencies of the biocatalysts can be considerably improved by DNA shuffling methods, and focuses on the green credentials of the process.

The process has been scaled up to 2000L scale at a subcontractor.