Control of the exo and endo pathways of the Diels-Alder reaction by antibody catalysis.
Catalytic antibodies that control the reaction pathways of the Diels-Alder cycloaddition have been generated. One antibody catalyzes the favored endo and the other the disfavored exo pathway to yield the respective 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 excellent 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 individual reactants and their relation to each other. In the case of the disfavored process, binding energy must be used to reroute the reaction along a higher energy pathway. The rerouting of reaction pathways has become a major focus of antibody catalysis and other disfavored reactions can be expected to be catalyzed so long as the energy barrier is not extreme. The energy requirements needed for absolute control of all of the stereoisomers of many Diels-Alder reactions fall in the energy range (approximately 20 kilocalories per mole) deliverable by antibody binding.
Gouverneur
V E
VE
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Houk
K N
KN
de Pascual-Teresa
B
B
Beno
B
B
Janda
K D
KD
Lerner
R A
RA
D020106:Acrylamide; D000178:Acrylamides / Q000737:chemistry; D000818:Animals; D017151:Antibodies, Catalytic / Q000737:chemistry*; D002384:Catalysis; D006241:Haptens / Q000737:chemistry; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D013237:Stereoisomerism; D013816:Thermodynamics; D014520:Urethane / Q000031:analogs & derivatives / Q000737:chemistry
D000178:Acrylamides; D017151:Antibodies, Catalytic; D006241:Haptens; D020106:Acrylamide; D014520:Urethane; C017963:vinyl carbamate