Stereoselectivity antibody catalysis

Zhang X, Deng Q, Yoo SH, Houk KN. Origins and predictions of 108. stereoselective antibody catalysis theoretical analysis of Diels-... 

For the purposes of this treatise, the definition of asymmetric synthesis is a modification of that proposed by Morrison and Mosher [1] and as such will be applied to stereospecific reactions in which a prochiral unit in either an achiral or a chiral molecule is converted, by utility of other reagents and/or a catalytic antibody, into a chiral unit in such a manner that the stereoisomeric products are produced in an unequal manner. As such, the considerable body of work devoted to antibody-catalysis of stereoselective reactions including chiral resolutions, isomerizations and rearrangements are considered to be beyond the scope of this discussion. For information regarding these specific topics and more general information regarding the catalytic antibody field the following papers... 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

Although attempts to catalyze bimolecular aldol condensations without resorting to enamine chemistry have not yet been successful, the Schultz group92 has prepared an antibody against the phosphinate hapten 115 that catalyzes the retro aldol reaction of 116 (kcJKm = 125 M-1 s l). The equilibrium in this case strongly disfavors the condensation product, and a histidine induced in response to the phosphinate may be involved in catalysis. Interestingly and in contrast to the previous examples, the stereoselectivity of the antibody is modest. The syn diastereomer of 116 was found to be the better substrate for the antibody by 2 1 over the anti diastereomer, but no evidence of enantioselectivity was observed. 

MIPs find uses in four main types of application separation of molecules, preparation of antibody analogues, recognition elements for sensors, stereoselective reactions and catalysis. 

Another new development in enzymatic reactions is the use of monoclonal antibodies as catalysts. These antibodies show regio- and stereoselectivity, substrate specificity, and rate acceleration. Hilvert12 has discussed three different reactions that are catalyzed by these antibodies decarboxylation, Dicls-Alder reactions, and Claisen rearrangements. This catalysis is a new field with tremendous possibilities. 

The control of chemical selectivity is a classical problem in organic chemistry and an antibody s ability to route reactions via disfavored pathways, as in the asymmetric Diels-Ald reaction, has important practical ramifications. Not surprisingly, extension of this approach to the catalysis of other unselective or energetically demanding reactions has become an important focus of research. Syn eliminations [45], cationic olefin cycliza-tions [46], and enol ether hydrolyses [47] are among the processes that have been investigated. For the purposes of the current discussion, however, the regio- and stereoselective reduction of the diketone 21 [48] illustrates what... 

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