Stereoselective Bioreduction to a Chiral Building Block on a Kilogram Scale

Abstract

The highly stereoselective bioreduction of ethyl cyclohexanone-2-carboxylate (1) on a kilogram scale is described. Ethyl(1S,2S)-trans-2-hydroxycyclohexane carboxylate (2) was prepared in 56% yield with a diastereomeric ratio (dr) of 99:1 and an enantiomeric ratio (er) of 99.5:0.5 after rectification. The cell growth and the biotransformation were performed in a large wave bioreactor equipped with a 200 l cell bag at Novartis Pharma AG, while the different purification steps were performed at the FHBB (Muttenz). The fourth semester chemistry students at the FHBB were actively involved in the preparation and optimization of the entire process.

Keywords

• Biotransformation
• High stereoselectivity
• Scale-up process
• S. pombe yeast
• Wavebioreactor