Hydrolysis of nitriles and epoxides

The hydrolysis of aliphatic and aromatic nitriles into amides and/or carboxylic acids is an area of rapidly increasing interest. Already the Nitto Chemical Industry Co. Ltd. has developed a large-scale process for the conversion of acrylonitrile into acrylamide using Rhodococcus cells (see Section 6.7.2). Many other organisms, as well as the nitrilases, nitrile hydratases and amidases derived from them, can effect similar conversions. It is interesting to note that for dinitriles, only one of the nitrile groups 

The hydrolysis of epoxides to give 1 -diols is an area that is ripe for development. Some work has been published showing that epoxides such as cyclohexane epoxide (36) form optically active diols, in this case cyclo-hexane-(lR,2i )-diol (37). The research has concentrated on the use of enzymes present in liver microsomes, and while this elegant work has indicated what can be achieved, it is clear that rapid progress and the involvement of non-experts in this particular area must await the discovery of readily available epoxide hydrolase enzyme(s) from microbial sources. 

The hydrolyses of esters, amides, and nitriles involve very simple procedures that are easy to perform, even by the non-specialist Similarly, the formation of esters using lipases is a process that can be considered to be absolutely straightforward. The reactions can be conducted under very mild conditions, and the regioselectivities and stereoselectivities that can be obtained are such that these procedures are becoming quite commonplace for the production of chemically and optically pure intermediates and end-products. 

The optical purity of a compound, be it an intermediate or end-product, can be expressed as the enantiomeric excess. It is noteworthy that during a kinetic resolution [S= S -I- P ], the enantiomeric excess of the product (P ) or recovered substrate (S ) will depend on the extent of conversion (c). Charles Sih introduced the term enantiomeric ratio , E, which is independent of the degree of conversion and is a very useful way of expressing the selectivity of an irreversible transformation. The value for E is calculated as follows  

It should be emphasized that the examples cited in this chapter are typical of many hundreds of biotransformations that have appeared in the literature over the past 10 years. Texts featuring comprehensive reviews of the subject matter that has been outlined in this chapter are listed in the Bibliography. 

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There are many types of enzyme-catalysed hydrolysis reactions. In this chapter, the hydrolysis of esters and amides will be surveyed quite extensively, while the hydrolysis of nitriles and epoxides will be mentioned briefly at the end. The use of hydrolase enzymes in organic solvents will be discussed also, in connection with the preparation of esters and amides. 

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