Enzymes chiral catalysts

In addition to the homogeneous and heterogeneous TM catalysts discussed above, other catalysts/methods such as uano catalysts, carbon materials, enzymes, chiral catalysts and continuous flow techuiques have also been developed successfully and applied in /-alkylation reactions of amines/amides with alcohols. 

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. 

Several approaches to enantioselective synthesis have been taken, but the most efficient are those that use chiral catalysts to temporarily hold a substrate molecule in an unsymmetrical environment—exactly the same strategy that nature uses when catalyzing reactions with chiral enzymes. While in that unsymmetrical environment, the substrate may be more open to reaction on one side than on another, leading to an excess of one enantiomeric product over another. As an analog)7, think about picking up a coffee mug in your... 

In the contemporary production of enantiopure compounds this feature is highly appreciated. Currently, kinetic resolution of racemates is the most important method for the industrial production of enantiomerically pure compounds. This procedure is based on chiral catalysts or enzymes, which catalyze conversion of the enantiomers at different rates. The theoretical yield of this type of reaction is only 50%, because the unwanted enantiomer is discarded. This generates a huge waste stream, and is an undesirable situation from both environmental and economic points of view. Efficient racemization catalysts that enable recycling of the undesired enantiomer are, therefore, of great importance. 

The development of catalytic asymmetric reactions is one of the major areas of research in the field of organic chemistry. So far, a number of chiral catalysts have been reported, and some of them have exhibited a much higher catalytic efficiency than enzymes, which are natural catalysts.111 Most of the synthetic asymmetric catalysts, however, show limited activity in terms of either enantioselectivity or chemical yields. The major difference between synthetic asymmetric catalysts and enzymes is that the former activate only one side of the substrate in an intermolecular reaction, whereas the latter can not only activate both sides of the substrate but can also control the orientation of the substrate. If this kind of synergistic cooperation can be realized in synthetic asymmetric catalysis, the concept will open up a new field in asymmetric synthesis, and a wide range of applications may well ensure. In this review we would like to discuss two types of asymmetric two-center catalysis promoted by complexes showing Lewis acidity and Bronsted basicity and/or Lewis acidity and Lewis basicity.121... 

Many enzymes need cofactors. Here again, a nonenzymic chiral catalyst functioning without a cofactor would offer an advantage. 

A major advantage that nonenzymic chiral catalysts might have over enzymes, then, is their potential ability to accept substrates of different structures by contrast, an enzyme will select only its substrate from a mixture. Striking examples are the chiral phosphine-rhodium catalysts, which catalyze die hydrogenation of double bonds to produce chiral amino acids (10-12), and the titanium isopropoxide-tartrate complex of Sharpless (11,13,14), which catalyzes the epoxidation of numerous allylic alcohols. Since the enantiomeric purities of the products from these reactions are exceedingly high (>90%), we might conclude... 

Perhaps the only distinct advantage of enzymic catalysts is their (occasionally) very high turnover rate in situ. Thus, the molar activity (formerly called the turnover number) of some enzymes approaches 36,000,000/min/molecule (7). This latter number pertains to carbonic anhydrase C, the enzyme that converts C02 to HC03 . However, chemists do not need enzymes to convert COz to HCO3-, as long as we are not considering in vivo reactions. Since many enzymes have molar activities as low as 1150/min/molecule, we need not consider molar activities of 100 to 500 (for nonenzymic catalysts) as a severe handicap. It is evident that enzymes and nonenzymic chiral catalysts, rather than being competitors, complement one another. 

Interestingly, enzymes are chiral catalysts and their potential for enantio-selective polymerization has been investigated [93]. Several examples are reported where a racemic mixture of lactones is polymerized by enzymatic polymerization to afford the corresponding optically active polyester [93]. For instance, lipase CA (Novozym 435) catalyses the ROP of racemic 4-methyl-s-caprolactone and 4-ethyl-s-caprolactone in bulk at 45 °C and 60 °C to afford (S )-eiuiched poly(4-methyl-e-caprolactone) and poly(4-ethyl- -caprolactone) with an enantiomeric purity higher than 95% [153]. 

Asymmetric induction is the use of a chiral reagent or catalyst to convert an achiral reactant to a chiral product having an excess of one enantiomer. In biochemistry the chiral catalyst is often en enzyme. For example. 

Catalysts and enzymes Chiral synthesis BINAP" Novozym 388 2,2 -Bis (diphenylphosphino) l,l -binaphthyl 1,3-Specific lipase Rhodia, France Solvias, Switz. Novozymes, Denmark... 

Enzymes as chiral catalysts play a role in all three methods. In nature enzymes catalyse all production of chiral compounds. In the laboratory enzymes can catalyse asymmetric synthesis, as well as resolve racemates. Which of the three methods is chosen in different cases depends on several factors, like price of starting materials, number of synthetic steps, available production technology and know-how etc. There is at present a constant ongoing development of synthetic methods and biotransformation is one field. Utilization of method i) requires knowledge of classical organic synthesis, enzymes have already played their role. Enzymes may play a part both in asymmetric synthesis and resolution. 

Although the use of enzymes as chiral catalysts will undoubtedly increase as they become more available, nonenzymic catalytic asymmetric synthesis is a very powerful tool in organic chemistry. 

Optically inactive reactants with achiral catalysts or solvents yield optically inactive products. With a chiral catalyst, e.g., an enzyme, any chiral product will be optically active. 

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