Catalytic, Enantioselective Aldol Reaction with an Artificial Aldolase Assembled from a Primary Amine and an Antibody

Article abstract of DOI:10.1021/jo00126a057

The aldol addition of acetone to aldehydes 1-5 is catalyzed by primary amine 14.The pH profile is consistent with catalysis by the free amine, with pK_a=8.55 for its conjugate acid.The catalytic cycle involves rate-determining coupling of the aldehyde with enamine III formed by condensation of the amine and acetone.Condensation with the aldehyde to form imine 16 inhibits catalysis (k₁₆=7.8 mM).Assembly of amine 14 with an antibody against quaternary ammonium hapten 19 yields an artificial aldolase which catalyzes the reaction.The catalyst is approximately 600 times more reactive than amine 14 alone.The pK_a of the amino group is unged within the complex.The antibody catalyzes the formation of amino nitrile 17 in the presence of cyanide, suggesting that condensation of acetone with amine 14 is favored by complexation with the antibody, an effect which might account for catalysis.The reaction with aldehyde 1 is si enantioface selective and gives aldol (SS)-6 (>95percent de) from (S)-1 and aldol (RS)-6 from (R)-1 (65percent de) in 1:2.8 ratio.These experiments show the principles of a novel approach for the design of an artificial aldolase.