ANTIBODY CATALYSIS OF MULTISTEP REACTIONS - AN ALDOL ADDITION FOLLOWED BY A DISFAVORED ELIMINATION

摘要

The intramolecular aldol condensation of keto-aldehyde 1 yields a substituted 2-benzyl-3-hydroxy-cyclohexanone 2 and subsequently 2-benzyl-2-cyclohexenone (3). The sequence involves four individual reaction steps, Three of these steps can be accelerated using general acid-base catalysis to effect proton transfer at or near the alpha-carbon of the ketone involved in the condensation, which is at the homobenzylic position relative to the aromatic group of the substrate (Ar). An antibody to the corresponding N-benzyl-N-methylpiperidinium hapten 5 was found to catalyze the entire reaction sequence. This antibody seems to act purely as a general base and does not catalyze the carbon-carbon bond forming step. Catalysis of the aldol elimination is selective for the disfavored trans-elimination with a single enantiomer of stereoisomer 2a. Catalysis is suppressed by incubating the antibody with a carboxyl-specific reagent, suggesting that a carboxyl group acts as a general base to catalyze the sequence. The antibody is approximately 2.0 x 10(5) times more reactive than acetate for catalysis of the sequence. These experiments demonstrate that catalysis of reactions with several consecutive transition states is possible using catalytic antibodies. [References: 42]