Lipase-catalyzed kinetic resolution of thiotetronic acid derivatives bearing a chiral quaternary carbon: total synthesis of ( R)-thiolactomycin and its O-analogue

Abstract

We have developed a chemoenzymatic synthesis of ( R)-thiolactomycin ( 1) having a chiral quaternary carbon atom at C5. In the kinetic resolution of the thiotetronic acid precursor 4, both enantiomers were obtained with high enantiomeric excess by use of Chirazyme ® L-2. Chemical transformations of the ( R)-alcohol 4 provided the chiral ( R)-thiolactomycin ( 1) in 36% yield in five steps.