Traditional Chemical Synthesis

When compared to traditional chemical synthesis, processes based on biocatalysts are generally less reliable. This is due, in part, to the fact that biological systems are inherently complex. In bioprocesses involving whole cells, it is essential to use the same strain from the same culture collection to minimise problems of reproducibility. If cell free enzymes are used the reliability can depend on the purity of the enzyme preparation, for example iso-enzyme composition or the presence of other proteins. It is, therefore, important to consider the commercial source of the enzyme and the precise specifications of the biocatalyst employed. 

In terms of process technology, biotechnology differs substantially from traditional chemical synthesis. Biopharmaceuticals cannot be produced in conventional multipurpose hne-chemical plants. As shown in Table 4.4, the specihcations of the two plant and process types are almost totally different. Therefore, the entry barriers are high. 

An example of this approach is Archer Daniels Midland, which reduced total production costs by over 60 percent by replacing traditional chemical synthesis with an advanced biological fermentation process for the manufacture of L-lysine. 

In summary, the nucleoside phosphorylases provide a regio- and stereo-specific route for nucleoside synthesis which is applicable to nucleoside analogs which are modified in either the base or the sugar moiety. These processes provide good yields of products in most cases without the extensive protection and deprotection steps involved in traditional chemical synthesis of nucleosides. Application of this strategy to the synthesis of 2 -deoxy- and 2, 3 -dideoxynucleosides was reported with the use of N-deoxyribosyl transferase from Lactobacillus species1301, 312). 

Our interest in GOase came from a need to find an efficient process for making 5-C-hydroxymethyl-L-arabino-hexopyranose derivatives 1 (Equation 1). These compounds have been developed as candidates for nonnutritive sugar substitutes in foods because they resist metabolism and have sucrose-like functional properties (7). These materials would be too expensive if made using the techniques of traditional chemical synthesis, so we developed a simple "one-pot" process (Equation 1) using GOase. 

Although the yield is low, the yield can be increased to 70 % after the electrolysis conditions are optimized. Electrochemical DNPOH synthesis method is greener and cheaper than the traditional chemical synthesis method, because, in electrochemical processes, sodium nitrite consumption can be reduced from 10... 

Most enzymatic reactions are performed under mild conditions, such as in water, at room temperature, and at atmospheric pressure, leading to lower energy consumption and operational risks. In addition, it is widely known that enzymes are capable of catalyzing highly regio-, chemo-, and enantio-selective reactions without performing the lengthy chemical protection/ deprotection steps required in traditional chemical synthesis. 

First we shall consider reactions for traditional chemical synthesis of peptides and then we look at reactions used in automated solid-phase peptide synthesis. The method for solid-phase peptide synthesis was invented by R. B. Merrifield (Rockefeller University), for which he earned the 1984 Nobel Prize in Chemistry. Solid-phase p>eptide synthesis reactions are so reliable that they have been incorporated into machines called peptide synthesizers (Section 24.7D). 

Traditional chemical synthesis strives for a single pure compound and is often motivated by some expectation about the desired physicochemical property or biological activity of the target compound. A new manner of chemical synthesis, combinatorial chemistry, developed from automation and recent advances in information technology. In combinatorial chemistry, a plethora of well-defined compounds can be synthesized in a single procedure, which can then be used to search for new materials or active compounds. 

Biocatalysis is the other option when selectivity (sterio or regio) is a priority in a reaction. The various aspects of biocatalysis are discussed elsewhere in the book the following are some examples of biocatalysts that have been used in important synthesis. Kirner (1995) conducted microbial ring hydroxylation and side chain oxidation of hetero-aromatics (see Fig. 3.18). Such selectivity is difficult to achieve in one step in traditional chemical synthesis. 

As mentioned previously, the challenge of creating molecular diversity is a considerable one, requiring strategies that differ from those used in the majority of traditional chemical synthesis. Since the conception of DOS, two distinct strategies for the generation of molecular and particularly skeletal diversity have been identified in the literature. They are... 

In sialoside synthesis, the use of enzymes can dramatically reduce the multiple protection-deprotection steps and provide great stereo- and regio-selectivity. Many enzymes accept uimatural substrates. Genetic engineering can further alter their stability, broaden their substrate specificity, and increase their specific activity [73]. Therefore, chemoenzymatic approaches using enzymes in combination with classical carbohydrate chemistry opened up a new venue, avoiding many of the problems encountered in traditional chemical synthesis. 

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