Jt. Ylikauhaluoma et al., ANTI-METALLOCENE ANTIBODIES - A NEW APPROACH TO ENANTIOSELECTIVE CATALYSIS OF THE DIELS-ALDER REACTION, Journal of the American Chemical Society, 117(27), 1995, pp. 7041-7047
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.