Catalysis: A Review of Chemical Literature
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For biological systems, trial and error has again been used, but often there are subtle differences between very similar enzymes so that interpretation of the results can be difficult. Examples of this are provided by baker's yeast reductions and pig liver esterase. More recently, our understanding of active sites and how to manipulate them either in a controlled or random way has allowed for the expansion of biomethods to make useful compounds.
Modern screening methods make it almost as easy to determine whether a chemical or a biocatalyst is capable of the desired transformation.
However, chemical approaches will often require a more involved analysis, such as high-performance liquid chromatography HPLC. Although biocatalysts may also need this type of analytical method, much faster methods have been developed and even the survival of the strain can be used. Closely related to this consideration is the ability of one system to perform a transformation that is very difficult for the other to accomplish. Examples are the hydrolysis of a meso -diester and the coupling of aryl groups.
In the first case, chemical catalysts have been developed to hydrolyse just one ester group of a diester to provide a chiral monoester. In the example of aryl couplings, there are many examples and variations of palladium-catalysed Heck and Suzuki reactions 5 , 6 , to name but two of these types of reaction; these approaches are the methods of choice in most cases. There are very few examples of enzymatic aryl couplings and, thus, this will only be used when alternative chemical methods are not applicable. Another criterion used to decide what type of catalyst is used is that the process must include isolation of the product in acceptable yield and purity.
Although significant advances have been made for the use of enzymes in the presence of organic solvents and with substrates that are poorly soluble in aqueous media, problems can still exist. Conversely, if the product is very water soluble, isolation of the desired material can present a significant challenge. Chemical transformations usually have the advantage of a number of solvent systems being available to perform the transformation and subsequent isolation. The scale-up of chemical catalytic reactions is usually an exercise in normal process chemistry.
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Synthesis of the ligands and transition metal catalyst usually present few problems, as the amounts are much lower than for the reaction itself. However, to improve specificity and efficiency new catalysts have to be prepared and tried. This can be a time-consuming exercise. On the biocatalytic side, modifications to the original enzyme can be made by genetic modifications and rapid screening. This allows selectivity, stability and other issues to be addressed. On the other hand, these studies can be time-consuming and may require more resources than just making a new ligand. The criteria of cost and speed also contribute to the choice of catalyst system.
In the early stages of development of a drug candidate, speed is of the essence but cost is still important. Precedence and the availability of the catalyst will be key factors. For larger scale work, the pendulum may swing from a chemical method to a biocatalytic one.
Homogeneous and Heterogeneous Catalytic Processes Promoted by Organoactinides
For commercial production, biological routes are often cost effective. However, it must be remembered that the catalytic step is usually part of a synthetic sequence. The substrate for the catalytic step has to be prepared and the product converted to the final target molecule.
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Advances in Catalysis. H-index: 0 CiteScore: 4.