ANTI-METALLOCENE ANTIBODIES - A NEW APPROACH TO ENANTIOSELECTIVE CATALYSIS OF THE DIELS-ALDER REACTION

We have shown how a constrained bicyclo[2.2.2]octene hapten can elicit antibody catalysts for the Diels-Alder reaction between 4-carboxybenz yl trans-1,3-butadiene-1-carbamate and N,N-dimethylacrylamide (Gouvern eur, V. E,; de Pascual-Teresa, B.; Beno, B.; Janda, K. D.; Lerner, R. A. Science 1993, 262, 204). In the present study we have developed a n ew approach to hapten design for elicitation of Diels-Alder catalytic antibodies. Our strategy was to engage the freely rotating eta(5)-cycl opentadienyl iron complex as the haptenic group. By applying such a fl exible hapten we set out to determine if the immune system could freez e out a conformer which mimics the Diels-Alder transition state and he nce produce new Diels-Alderases. If so, how would the catalytic rates, diastereo- and enantioselectivity of these antibodies compare with th ose of antibodies elicited by the former methodology? We generated ant ibodies that catalyzed the Diels-Alder reaction with high enantio- and diastereoselectivity and had effective molarities (EM) comparable to those of antibodies elicited using the constrained bicyclo[2.2.2]octen e haptens. This methodology offers a new approach to the production of antibodies for the catalysis of other reactions with pericyclic, high ly-ordered transition states.