Microbial transformations 59: First kilogram scale asymmetric microbial Baeyer-Villiger oxidation with optimized productivity using a resin-based in situ SFPR strategy

This study is demonstrating the scale up of asymmetric microbial Baeyer‐Villiger oxidation of racemic bicyclo[3.2.0]hept‐2‐en‐6‐one (1) to the kilogram scale using a 50 L bioreactor. The process has been optimized with respect to bottlenecks identified in downscaled experiments. A high productivity was obtained combining a resin‐based in situ substrate feeding and product removal methodology (in situ SFPR), a glycerol feed control, and an improved oxygenation device (using a sintered‐metal sparger). As expected both regioisomeric lactones [(−)‐(1S,5R)‐2 and (−)‐(1R,5S)‐3] were obtained in nearly enantiopure form (ee > 98%) and good yield. This represents the first example of such an asymmetric Baeyer‐Villiger biooxidation reaction ever operated at that scale. This novel resin‐based in situ SFPR technology therefore clearly opens the way to further (industrial) upscaling of this highly valuable (asymmetric) reaction. © 2005 Wiley Periodicals, Inc.