Chemoenzymatic processes

Tao, J., Zhao, L. and Ran, N. (2007) Recent advances in developing chemoenzymatic processes for active pharmaceutical ingredients. Organic Process Research Development, 11, 259-267. 

Figure 8.9 Chemoenzymatic process forproduction of high-purity glycolic acid employing Acidovorax facilis 72W Phel68Val nitrilase...

An Integrated Approach to Developing Chemoenzymatic Processes at the Industrial Scale... 

Catabolic enzyme NANA aldolase catalyses cleavage of NANA to form NAM and pyruvic acid, the latter being a more attractive material for a chemoenzymatic process. It has long been known that the reverse reaction may be used for NANA synthesis. However, this approach to a manufacturing process also has complications. 

This review covers the recent literature (2002-2007) in which either multienzyme systems or, alternatively, true chemoenzymatic processes (i.e. those in which an enzyme is combined with a chemical catalysts/reagent in a key step) are employed for the synthesis of chiral amino acids and amines. Not included are those papers in which the term chemoenzymatic refers to the fact that the substrate for the biotransformation has simply been prepared via chemical synthesis. 

Chemoenzymatic processes, where oxidases are used in single steps within processes for production of synthetic compounds, including production of chiral products. 

Chemoenzymatic processes involving oxidizing enzymes have been reported particularly for specific chemical syntheses. For example, industrially important amino acids can be deracemized by exploiting the enantioselectivity of amino acid oxidases a commercial process has recently been developed in which efficient... 

Epoxide hydrolases are less used than lipases however, in recent years the synthesis of chiral diols with these biocatalysts has emerged as an excellent methodology to develop new and interesting chemoenzymatic processes [13],... 

Sustainable Chemoenzymatic Processes for Statin Side Chains... 

The Development of Short, Efficient, Economic, and Sustainable Chemoenzymatic Processes... 

Figure 7.4 Chemoenzymatic process to 1,5-dimethyl-2-piperidone (1,5-DMPD) (Thomas, 2002).

One of the inherent advantages of enzymes is the ability to discriminate between stereoisomers, often generating products with ena-tiomeric excesses (i.e., of over 98%). Judicious application of biocatalysis can also reduce the number of chemical steps needed to synthesize certain drugs, leading to hybrid chemoenzymatic processes with lower costs and less waste. The range of enzymes used in the synthesis of chiral intermediates has expanded beyond esterases and acylases and... 

The replacement of the traditional, chemoenzymatic process for 7-ADCA by a biotransformation, preferably in the course of the fermentation, was greatly desired [122] but far from trivial to accomplish. It should be noted that the enzymatic ring expansion step (see Fig. 8.25) is not very selective, and the productivity is modest even in natural cephalosporin producing organisms. 

Moreover, this chemoenzymatic process yields new aminonucleosides that are very difficult to prepare by chemical procedures alone [15). Scheme 10.3 shows a general chemoenzymatic procedure for obtaining 3 -amino-xylo-nucleosides. The key step is based on the 5 -directed intramolecular nucleophiUc substitution at the 3 -activated position of the nucleoside. This methodology is applicable to ribonu-cleosides and 2 -deoxyribonucleosides and shows the utility of a combination of... 

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