Bioconversion dinitrile

Bergeron S, Chaplin D, Edwards JH, Ellis BS, Hill CL, Holt-Tiffin K, Knight JR, Mahoney T, Osborne AP, Ruecroft G (2006) Nitrilase-catalyzed desym-metrization of 3-hydroxyglutaronitrile preparation of a statin side-chain intermediate. Org Proc Res Dev 10 661-665 Burns M, Weaver J, Wong J (2005) Stereoselective enzymic bioconversion of aliphatic dinitriles into cyano carboxylic acids. WO 2005100580 DeSantis G, Zhu Z, Greenberg W, Wong K, Chaplin J, Hanson SR, Farwell B, Nicholson LW, Rand CL, Weiner DP, Robertson D, Burk MJ (2002) An enzyme library approach to biocatalysis development of nitrilases for enantioselective production of carboxylic acid derivatives. J Am Chem Soc 124 9024-9025... 

Several investigators using enzymes of different microbial origin have reported on the monohydrolysis of dinitriles to the corresponding cyano-carboxylic acids in high yields. Selective hydrolysis of one cyano group of a dinitrile is very difficult to carry out by chemical hydrolysis and is, therefore, an intriguing aspect of nitrile bioconversion. 

Aliphatic nitrile hydratases, that catalyzed the hydrataiion of nitriles to amides, were purified and characterized in Arthrobacter sp. J1 [128], Brevibacterium R312 [129], and Rhodococcus sp. N774 [130]. In tixe first strain, the activity of an amidase, which forms acetic add and ammonia stoichiometrically from acetamide, was also detected [131]. Bioconversion of dinitrile to mononitrile catalyzed by nitrile hydratase and amidase was obtained from Corynebacterium sp. C5. The two enzymes were constitutively formed in cells [132]. 

Compared to a maximal bioconversion yield of 50% in racemic resolutions, asymmetric syntheses have a theoretical yield of 100%. Such an ideal yield was nearly reached with another R. rhodochrous ATCC 21197, which transformed disubstituted malononitriles such as butylmethylmalononitrile to the corresponding (7 )-amide carboxylic acid with high enantiomeric excesses and yields [80]. The reaction proceeded via a fast, nonstereospecific hydration of the starting dinitrile followed by a slow, enantioselective hydrolysis of the diamide intermediate by the amidase (Fig. 27). 

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