Enzymatic resolution and evaluation of enantiomers of cis-5′-hydroxythalidomide

The straightforward synthesis of both enantiomers of cis-5′-hydroxythalidomide, a major metabolite of thalidomide, has been accomplished by enzymatic kinetic resolution of a racemic substrate catalyzed by Pseudomonas stutzeri lipase TL. cis-5′-Hydroxythalidomide shows resistance to racemization (and epimerization) at physiological pH. A tube formation assay to assess the ability to inhibit angiogenesis revealed that cis-5′-hydroxythalidomides are inactive.