Chemoenzymatic Synthesis of Chiral Building Blocks Based on the Kinetic Resolution of Glycerol-Derived Cyclic Carbonates

The biocatalytic kinetic resolution of cyclic carbonates derived from glycerol is reported. A selection of 26 esterases and lipases was tested for the asymmetric hydrolysis of the model substrate (epichlorohydrin carbonate) in aqueous medium. Among them, Pig Liver Esterase and Novozym (R) 435 showed the best selectivity with E=38 and 49, respectively. Both enzymes were employed for the conversion of 12 glycerol derivatives under optimized conditions. The resolution of halogenated carbonates afforded the unconverted enantiomer in up to >99 : 1 er. Furthermore, Novozym (R) 435 was successfully recycled 10 times without significant loss of activity. Upscaling and isolation of the chiral carbonate was also demonstrated. Subsequent conversion of this chiral building block allowed the direct one-pot synthesis of (S)-Guaifenesin, (S)-Mephenesin and (S)-Chlorphenesin in up to 89 % yield and 94 : 6 er.