Enzyme-like catalysts

In the early work on the synthesis of prostaglandins, zinc borohydride was used for the reduction of the 15-ketone function and a 1 1 mixture of epimeric 15(S)- and 15(/ )-alcohols was generally obtained. Subsequent studies led to reaction conditions for highly selective reduction to the desired 15(S)-alcohol. Some of the results are summarized in the following table. The most practical method is E which utilizes borane as the stoichiometric reductant and a chiral, enzyme-like catalyst which is shown. 

The antibody-catalyzed Diels-Alder reaction developed by Schultz utilized a Diel-Alderase enzyme-like catalyst evolved from an antibody-combining site (Eq. 12.13). The idea is that the generation of antibodies to a structure that mimics the transition state for the Diels-Alder reaction should result in an antibody-combining site that lowers the entropy of activation by binding both the diene and dienophile in a reactive conformation. 

There are two basic reasons for attempting to make enzyme-like catalysts from nonbiological materials. First, the preparation of inexpensive, stable catalysts with high efficiency would be of obvious practical benefit. Second, the modeling of enzymes has provided new concepts and valuable confirmation of concepts arrived at by enzymologists. Additional supportive work and new ideas are expected in the future. 

Attempts to make enzyme-like catalysts, synzymes, from nonbiological systems is described by G. P. Royer. The final two chapters by Y. Yamazaki and T. Kawai, and Z. Paal deal with catalytic hydrocarbon conversions using acids and metals, respectively, as catalysts. 

F. Hollfelder, A. J. Kirby, and D. S. Tawfik, On the magnitude and specificity of medium effects in enzyme-like catalysts for proton transfer,/. Org. Chem. 2001, 66, 5866-5874. 

Corey and Reichard described a more efficient synthesis of the fluoxetine enantiomers.15 This synthesis features a catalytic reduction of prochiral ketone 12 to install the correct absolute stereochemistry at C-3. In this respect this method is very similar to the one previously described by Robertson et al.10 However, the major advantage of the Corey procedure is that the reduction utilizes chiral enzyme-like catalysts to induce the correct stereochemistry and both enantiomers of the catalyst are available (15 and 16). 

Desirable catalyst characteristics in this field include catalytic sites with asymmetric transition-metal centers, which are conducive to stereospecific synthesis. An alternative, intermediate solution is the encapsulation of the thermally unstable enzyme like catalysts onto stable supports. 

These observations are preliminary—it is apparent however that this type of physical catalysis, possibly combined with a self-reproducing mechanism, is an interesting field of inquiry for the origin of life. In the design of a cell model, the enzyme-like catalyst should eventually operate inside the vesicle. The question then... 

We have been involved in the synthesis of metal-based enzyme-like catalysts for hydrolysis of peptide bonds of proteins. We have been interested in hydrolysis as the target reaction since only one molecule is involved as the substrate, except for the water molecule. We selected peptide bonds as the targets since protein hydrolysis is important in the era of genomics. Proteomics and peptide bonds are quite stable with a half-life (26, 27) of spontaneous hydrolysis at (pH 7 at 25°C)... 

Synthesis of polymeric enzyme-like catalysts with N-heterocyclic fragments as active centers 01SL1343. 

Ball ZT (2012) Designing enzyme-like catalysts a rhodium(II) metallopeptide case study. Acc Chem Res 46 560-570... 

They offer a unique access to artificial tailor-made enzyme-like catalysts and are able to catalyze reactions which have no equivalent counterpart within the diverse natural enzymes. 

More recently the B-alkyl compounds (84) formed by reaction of (83) with boronic acids have proved to be even more effective and stable catalysts. The mechanism for the catalytic cycle of the reduction is shown for (84, R=Me). Corey has coined the term chemzyme for this type of enzyme-like catalyst. 

The construction of enzyme-like catalysts requires the generation of highly selective binding sites containing an appropriate constellation of chemical groups. Since the de novo synthesis of enzymes with predictable... 

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