Aspartame synthesis

Proteases can be used for the synthesis of peptides in a way analogous to the ester synthesis catalysed by lipases. The most successful industrial example of enzymatic peptide synthesis is described in section 4.6 aspartame synthesis. In the industrial process in Europe the equilibrium position is shifted towards synthesis because the... 

There are a number of reported solid-to-solid reactions where products precipitated as salts rather than as neutral compounds. The thermolysin-catalyzed production of the potassium salt of Z-aspartame [51, 52], the commercialized process of aspartame synthesis, where a salt of cationic D-Phe-OMe and anionic Z-aspartame precipitates [53], and the enzymatic conversion of solid Ca-maleate to solid Ca-D-malate [44] are examples of such behavior. 

Ion-pair chromatography has also been used for the separation of aspartame from synthesis intermediates and degradation products. Lawrence and Iyengar (22) and Stamp and Labuza (23) used sodium heptanesulfonate to improve separation of aspartame from its decomposition products. Verzella et al. (21) used sodium hexanesulfonate and gradient elution to separate aspartame from two decomposition products and seven related synthesis by-products (Table 2). This method has been used routinely for the control of aspartame synthesis and as a check of purity of both finished bulk and mother liquor. 

Fine chemicals Aspartame synthesis Amino acid synthesis Antibiotics Protease (e.g. thermolysin) Aminoacylase Penicillin acylase... 

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. 

Aspartame synthesis on a large scale is achieved by the following reactions ... 

Use of peptide deformylase in aspartame synthesis. The cheap formyl group is used for protection and coupling proceeds chemically. After coupling, the formyl group of the desired product is selectively removed by peptide deformylase. 

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