Aspartame synthesis using enantioselective

The first protease-catalyzed reaction in ILs was the Z-aspartame synthesis (Scheme 10.7) from carbobenzoxy-L-aspartate and L-phenylalanine methyl ester catalyzed by thermolysin in [BMIM] [PF ] [ 14]. Subtilisin is a serine protease responsible for the conversion of A -acyl amino acid ester to the corresponding amino acid derivatives. Zhao et al. [90] have used subtilisin in water with 15% [EtPy][CF3COO] as cosolvent to hydrolytically convert a series of A -acyl amino acid esters often with higher enantioselectivity than with organic cosolvent like acetonitrile (Scheme 10.8, Table 10.2). They specifically achieved l-serine and L-4-chlorophenylalanine with an enantiomeric access (ee) of-90% and -35% product yield which was not possible with acetonitrile as a cosolvent [90]. Another example is hydrolysis of A-unprotected amino acid ester in the presence of a cysteine protease known as papain. Liu et al. 

Rhodium complexes that contain these ligands have demonstrated moderate to high enantioselectivities (24-96%) in the reduction of enamides to protected amino acids (Scheme 1) [7,54], Despite the moderate degree of asymmetric induction, an industrial process had been developed with this catalyst system by ANIC S.p.A. (EniChem) for the production of (S)-phenylalanine for the synthesis of aspartame [11.33], The process uses cationic Rh-7a for the reduction of 14b at 28 psig Hl and 22°C for 3 hours substrate/catalyst (S/C) = 15,000) to give 15b in 83.3% ee, which is enriched to 98.3% by reciystallization [56],... 

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