Ammonolysis 384 Chirality

Amino acids can be synthesized in racemic form by several methods, including ammonolysis of an a-bromo acid, alkylation of diethyl acetamido-malonate, and reductive amination of an cv-keto acid. Alternatively, an enantio-selective synthesis of amino acids can be carried out using a chiral hydrogenation catalyst. 

Over the past years, interest in the preparation of chiral amines and amides by enzymatic ammonolysis or aminolysis reactions [4] has greatly increased for academic and industrial sectors. The role that the enzymatic acylation of amines or ammonia plays for the preparation of some pharmaceuticals is noteworthy [5]. 

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). 

Asymmetrization of a prochiral dicarboxylic acid diester catalyzed by lipases, where the stereo center of the product is located on the acyl side, becomes a single-step process because the polar carboxylic acid and/or amide formed are not well accepted as substrates by the Upase. One example is the enantioselective hydrolysis or ammonolysis of diethyl 3-hydroxyglutarate, as shown in Scheme 7.4, a reaction which leads to the formation of a precursor for the important chiral side chain of atorvastatin, lipitor [40, 41]. The S-enantiomer was formed with high e.e. (98%), but unfortunately this is the undesired enantiomer for the production of the pharmaceutically important product. Only a-chymotrypsin gave a predominance of the... 

---