CONTROL OF THE EXO-PATHWAY AND ENDO-PATHWAY OF THE DIELS-ALDER REACTION BY ANTIBODY CATALYSIS

Catalytic antibodies that control the reaction pathways of the Diels-A lder cycloaddition have been generated. One antibody catalyzes the fav ored endo and the other the disfavored exo pathway to yield the respec tive cis and trans adducts in enantiomerically pure form. A comparison of the x-ray structure of the hapten with the calculated geometry of the transition structure showed that [2.2.2] bicyclic compounds are ex cellent mimics of the transition state of the Diels-Alder reaction. To achieve catalysis and the high degree of stereoselectivity shown here , the antibody must simultaneously control the conformation of the ind ividual reactants and their relation to each other. In the case of the disfavored process, binding energy must be used to reroute the reacti on along a higher energy pathway. The rerouting of reaction pathways h as become a major focus of antibody catalysis and other disfavored rea ctions can be expected to be catalyzed so long as the energy barrier i s not extreme. The energy requirements needed for absolute control of all of the stereoisomers of many Diels-Alder reactions fall in the ene rgy range (approximately 20 kilocalories per mole) deliverable by anti body binding.