Antibody catalysis of a reaction otherwise strongly disfavoured in water.
Several examples have been reported recently of antibody catalysis of reactions that are strongly disfavoured because of the high free energy of the transition state. Here we show that catalytic antibodies can be used to promote a particularly useful kind of reaction from a synthetic point of view: one involving an intermediate that is highly unstable in water. We show that an antibody elicited against the quaternary ammonium ion 4a (Fig. 1) catalyses the protonation of the enol ether 1 to form, with complete enantioselectivity, an oxocarbonium intermediate. This species is highly reactive in water, and would normally react with a water molecule to give the corresponding ketone 2. But the antibody provides a hydrophobic environment that allows the oxocarbonium ion instead to undergo an intramolecular reaction to form an enantiomerically pure ketal 3. This result shows that catalytic antibodies can exclude solvent molecules entirely from crucial steps on the reaction pathway.
Shabat
D
D
Department of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa.
Itzhaky
H
H
Reymond
J L
JL
Keinan
E
E
D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D002384:Catalysis; D004987:Ethers / Q000737:chemistry; D006241:Haptens / Q000276:immunology; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D017151:Antibodies, Catalytic; D000911:Antibodies, Monoclonal; D004987:Ethers; D006241:Haptens; D000644:Quaternary Ammonium Compounds; D012997:Solvents; D014867:Water