Racemic amines hydrolytic enzymes

Another possible mechanism for the racemization of amino acid esters involves the in situ, transient, formation of Schiff s bases by reaction of the amine group of an amino acid ester with an aldehyde. Using this approach, DKR of the methyl esters of proline 5 and pipecolic acid 6 was achieved using lipase A from C. ant-arclica as the enantioselective hydrolytic enzyme and acetaldehyde as the racemiz-ing agent (Scheme 2.4). Interestingly, the acetaldehyde was released in situ from vinyl butanoate, which acted as the acyl donor, in the presence of triethylamine. The use of other reaction additives was also investigated. Yields of up to 97% and up to 97% e.e. were obtained [6]. 

Alternative hydrolytic enzymes, such as amidases and acylases, have also been employed for the resolution of racemic amines. Unlike lipases, these enzymes are typically not commercially available but they can be isolated from microorganisms. 

Among the principal methods for the enzymatic synthesis of enantiomerically pure amino acids depicted in Scheme 2.10, the most widely applied strategy is the resolution of racemic starting material (synthetically prepared from inexpensive bulk chemicals) employing easy-to-use hydrolytic enzymes such as proteases, esterases, and lipases. In contrast, more complex procedures requiring special expertise are the (1) reductive amination of a-keto acids using a-amino acid... 

Since the beginning of enzyme catalysis in microemulsions in the late 1970s, several biocatalytic transformations of various hydrophilic and hydrophobic substrates have been demonstrated. Examples include reverse hydrolytic reactions such as peptide synthesis [44], synthesis of esters through esterification and transesterification reactions [42,45-48], resolution of racemic amino acids [49], oxidation and reduction of steroids and terpenes [50,51], electron-transfer reactions, [52], production of hydrogen [53], and synthesis of phenolic and aromatic amine polymers [54]. Isolated enzymes including various hydrolytic enzymes (proteases, lipases, esterases, glucosidases), oxidoreductases, as well as multienzyme systems [52], were anployed. 

Lipases have also been widely applied for the resolution of racemic chiral amines. In principle, these reactions can be carried out in both the hydrolytic mode as well as under conditions favouring acylation. As amines are more nucleophilic than alcohols, it is necessary to use less reactive acyl donors in order to minimize the background reaction of non-enzyme catalysed acylation, and in this respect it appears that simple esters such as ethyl acetate are optimal. 

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