Scale antibody catalyzed reaction

Antibody-catalyzed reactions, too, can be conducted on a gram scale (Reymond, 1994) the biocatalyst was separated by dialysis in a cellulose membrane (12-14 kDa, antibody 150 kDa) and reused. The enantioselective hydrolysis of the enol ether (4) to the ketone (5) ran with an e.e. of 89-91% (Figure 18.10). 

Spectroscopic or visible detection of antibody-catalyzed reactions enhances rapid characterization of catalysts on a small scale. Such detection systems are also useful for high-throughput screening for new aldolase antibody... 

Therefore several reactions were subjected to various antibody catalyses, e. g., ester and enol ether cleavage, transesteiification, ketone reduction. Cope rearrangement, ring closure via epoxide opening, or Diels-Alder cycloaddition [74, 75]. An exceptional reaction is the antibody-catalyzed Robinson annulation of triketone 28 to the Wieland-Miescher ketone 29 on a preparative scale. Surprisingly, even the alkylation of diketone 27 with methyl vinyl ketone was catalyzed by the same antibody, but at moderate rates (Scheme 15) [76]. 

When the reaction was performed on a 100 mg scale, the diene was obtained in 55% yield as a mixture of ( )- and (Z)-stereoisomers. However, when the scale was increased to lOOg, various by-products, such as cyclized products or alkyl group-migrated compounds, were produced presumably because of acid-catalyzed reactions of the diene. The formation of such by-products can be reduced using a microflow system composed of a micromixer and a microtube reactor. Thus, a solution of the allylic alcohol in tetrahydrofuran (THF) was mixed with a solution of p-toluenesulfonic acid (p-TsOH) in THF/toluene at 90 °C. After the reaction mixture was allowed to flow for 47 s, the reaction was quenched with a saturated NaHCOs solution at room temperature. In this case the desired diene was obtained in 80% yield. It is noteworthy that the acid-mediated by-products were not detected. This process was applied to the synthesis of pristane, a biologically important natural product that is widely used as an adjuvant for monoclonal antibody production. 

In this respect, reactions catalyzed by monoclonal antibodies have been the focus of much interest [72]. One of the first antibody-supported syntheses on a gram scale and with an enantiomeric excess of up to 99 % was the kinetic resolution of aldol adducts. The products resulting from the retro-aldol reaction served as precursors in the synthesis of epothilones A and B [73]. 

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