Aminolysis, enzymatic resolution

The enzymatic resolution of esters via aminolysis or ammonolysis processes represents an efficient alternative to the resolution of substrates by transesterification... 

Here, we have selected a few representative examples of the enzymatic resolution of esters by aminolysis or ammonolysis reactions. On the other hand, the enzymatic acylation of racemic amines is also of great utility for the preparation of optically pure... 

A number of enzymatic resolutions have been investigated to the chiral halo ester, including esterification, transesterification, and aminolysis.69246 250 Zeneca (ICI) has commercialized the approach that relies on a dehalogenase (Scheme 31.25).69,245,248 249... 

The resolution of racemic ethyl 2-chloropropionate with aliphatic and aromatic amines using Candida cylindracea lipase (CCL) [28] was one of the first examples that showed the possibilities of this kind of processes for the resolution of racemic esters or the preparation of chiral amides in benign conditions. Normally, in these enzymatic aminolysis reactions the enzyme is selective toward the (S)-isomer of the ester. Recently, the resolution ofthis ester has been carried out through a dynamic kinetic resolution (DKR) via aminolysis catalyzed by encapsulated CCL in the presence of triphenylphosphonium chloride immobilized on Merrifield resin (Scheme 7.13). This process has allowed the preparation of (S)-amides with high isolated yields and good enantiomeric excesses [29]. 

The strategy described here explains the different possibilities of enzymatic ammonolysis and aminolysis reaction for resolution of esters or preparation of enantiomerically pure amides, which are important synthons in organic chemistry. This methodology has been also applied for the synthesis of pyrrolidinol derivatives that can be prepared via enzymatic ammonolysis of a polyfunctional ester, such as ethyl ( )-4-chloro-3-hydroxybutanoate [30]. In addition, it is possible in the resolution of chiral axe instead of a stereogenic carbon atom. An interesting enzymatic aminolysis of this class of reaction has been recently reported by Aoyagi et al. [31[. The side chain of binaphthyl moiety plays an important role in the enantiodis-crimination of the process (Scheme 7.14). 

Ue 7.13 Dynamic kinetic resolution of 2-Chloropropionate by enzymatic aminolysis. 

The enzymatic KR is based on the reaction between the most favored enantiomer of a racemic amine and a suitable acyl donor in an organic solvent. The acylation of amines can also be considered as an aminolysis process, the examples for the KR on primary amines being more common in the literature than the resolution of secondary amines. From fhe hydrolases toolbox, lipases seem to be the most suitable enzymes due to the fact that they scarcely ever hydrolyze an amide bond [184,185], and, therefore, the reaction is practically irreversible. CAL-B has usually shown the best activity and selectivity for fhe resolution of racemic amines [186,187]. 

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