Design and Synthesis of Haptens for the Catalytic Antibody-Promoted Dynamic Kinetic Resolution of Oxazolin-5-ones



The synthesis of the first two haptens designed to elicit catalytic hydrolytic antibodies for the dynamic kinetic resolution of racemic 4-substituted 4H-oxazolin-5-ones is reported. A cyclic phosphinate and a 2,5-dihydro-1H-pyrrolium derivative were chosen as “first generation” haptens. The cyclic phosphinate was designed to mimic the higher energy transition state along the reaction coordinate for the hydrolytic process, while the dihydro-1H-pyrrolium group of the second hapten was selected to generate hydrolytic antibodies that might use a “bait and switch” mechanism. These two haptens were prepared successfully by use of a ring-closing metathesis reaction as the key step. This study is the first pilot investigation towards an antibody-promoted dynamic kinetic resolution and should allow the development of a new biocatalytic route to enantiomerically pure natural and unnatural amino acids.