L-Phenylalanine methyl ester

Aspartame (L-aspartyl-L-phenylalanine methyl ester [22839-47-0]) is about 200 times sweeter than sucrose. The Acceptable Daily Intake (ADI) has been estabUshed by JECFA as 40 mg/kg/day. Stmcture-taste relationship of peptides has been reviewed (223). Demand for L-phenylalanine and L-aspartic acid as the raw materials for the synthesis of aspartame has been increasing, d-Alanine is one component of a sweetener "Ahtame" (224). 

A solution of 88.5 parts of L-phenylalanine methyl ester hydrochloride in 100 parts of water is neutralized by the addition of dilute aqueous potassium bicarbonate, then is extracted with approximately 900 parts of ethyl acetate. The resulting organic solution is washed with water and dried over anhydrous magnesium sulfate. To that solution is then added 200 parts of N-benzyloxycarbonyl-L-aspartic acid-a-p-nitrophenyl, -benzyl diester, and that reaction mixture is kept at room temperature for about 24 hours, then at approximately 65°C for about 24 hours. The reaction mixture is cooled to room temperature, diluted with approximately 390 parts of cyclohexane, then cooled to approximately -18°C in order to complete crystallization. The resulting crystalline product is isolated by filtration and dried to afford -benzyl N-benzyloxycarbonvI-L-aspartyl-L-phenylalanine methyl ester, melting at about 118.5°-119.5°C. 

To a solution of 180 parts of -benzyl N-benzyloxycarbonyl-L-aspartvI-L-phenylalanine methyl ester in 3,000 parts by volume of 75% acetic acid is added 18 parts of palladium black metal catalyst, and the resulting mixture is shaken with hydrogen at atmospheric pressure and room temperature for about 12 hours. The catalyst is removed by filtration, and the solvent is distilled under reduced pressure to afford a solid residue, which is purified by re-crystallization from aqueous ethanol to yield L-aspartyl-L-phenylalanine methyl ester. It displays a double melting point at about 190°C and 245°-247°C. 

L-Asparaginyl-L-arginyl-L-valyl-L-tyrosyl-L-valyl-L-histidyl-L-prolyl-L-phenylalanine methyl ester trihydrochloride Angiotensin amide Atropic acid ethyl ester Tilidine HCI Atropine... 

Hayama et al.132 discussed the catalytic effects of silver ion-polyacrylic add systems toward the hydrolyses of 2,4-dinitrophenylvinylacetate 84 (DNPVA) by using the weak nudeophilicity of carboxylic groups and the change-transfer interactions between olefinie esters and silver ions133Metal complexes of basic polyelectrolytes are also stimulating as esterase models. Hatano etal. 34, 13S) reported that some copper(II)-poly-L-lysine complexes were active for the hydrolyses of amino acid esters, such as D- and L-phenylalanine methyl ester 85 (PAM). They... 

L-alpha-aspartyl-L-phenylalanine methyl ester. See aspartame 1-glutamic acid. See monosodium glutamate L-lysine, 90... 

C HiiNOj 63-91-2) see Melphalan Quinapril hydrochloride Saquinavir L-phenylalanine fert-hutyl ester hydrochloride (CijHtoCINOj 15100-75-1) see Alacepril D-phenylalanine methyl ester (CioHijNOj 21685-51-8) see Nateglinide L-phenylalanine methyl ester hydrochloride (C10H14CINO2 7524-50-7) see Angiolensinatnide... 

There are two catalytically active residues in pepsin Asp-32 and Asp-215. Their ionizations are seen in the pH-activity profile, which has an optimum at pH 2 to 3, and which depends upon the acidic form of a group of pKa 4.5 and the basic form of a group of pKa 1.1.160,161 The pKa values have been assigned from the reactions of irreversible inhibitors that are designed to react specifically with ionized or un-ionized carboxyl groups. Diazo compounds—such as A-diazoacetyl-L-phenylalanine methyl ester, which reacts with un-ionized carboxyls—react specifically with Asp-215 up to pH 5 or so (equation 16.28).162-164 Epoxides, which react specifically with ionized carboxyls, modify Asp-32 (equation 16.29). 

N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-leucyl-L-threonyl-N6-tosyl-L-lysine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-leucyl-L-threonyl-N6-tosyl-L-lysyl-L-aspartic p-nitrobenzyl diester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-phenylalanine methyl ester)-4-oyl]-... 

L-phenylalanyl L-phenylalanine methyl ester L-prolyl L-alanine methyl ester L-prolyl L-aspartic dibenzyl ester L-prolyl glycine ethyl ester L-prolyl methyl ester L-serylglycine ethyl ester... 

The 15N chemical shifts measured for the Schiff base being a derivative of gossypol [7] and L-phenylalanine methyl ester equal —243.7 ppm in CDC13 solution and —237.5 in solid state (relative to external... 

By contrast, L-phenylalanine methyl ester does not react with BENA generated from 1-nitropropane (R =H) due apparently to low nucleophilicity of the amino group. However, the N, C -coupling reaction of the ester of this amino acid with another internal BENA (R = CC>2Me) proceeds rather readily but is characterized by extremely low diastereoselectivity. Probably, the last N,C-coupling does not occur via an intermediate a-nitroso alkene but by a classical Michael addition to BENA MeCH=C(C02Me)N(05i )2 as to Michael substrate. 

Aspartame, N-a-L-aspartyl-L-phenylalanine methyl ester, trade names NutraSweet , and Aspartil , is a dipeptide derivative. Like dipeptides aspartame is metabolised into the constituents, i.e. amino acids and methanol. Therefore studies into the metabolic behaviour and the fate of metabolites were carried out. Levels of blood aspartate and glutamate were measured after intake of high aspartame doses. Changes were transient and allegations of influences of high aspartame levels on brain function could never be verified. 

The improvement of enzyme like MIP is currently another area of intense research. Beside the use of the MIP themselves as catalysts, they may also be applied as enhancer of product yield in bio-transformation processes. In an exemplary condensation of Z-L-aspartic acid with L-phenylalanine methyl ester to Z-aspartame, the enzyme thermolysin was used as catalyst. In order to shift the equilibrium towards product formation, a product imprinted MIP was added. By adsorbing specifically the freshly generated product from the reaction mixture, the MIP helped to increase product formation by 40% [130]. MIP can also be used to support a physical process. Copolymers of 6-methacrylamidohexanoic acid and DVB generated in the presence of calcite were investigated with respect to promotion of the nucleation of calcite. Figure 19 (left) shows the polymer surface with imprints from the calcite crystals. When employing these polymers in an aqueous solution of Ca2+ and CO2 the enhanced formation of rhombohedral calcite crystals was observed see Fig. 19 (right) [131]. 

Phenylalanine (Phe or F) (2-amino-3-phenyl-propanoic acid) is a neutral, aromatic amino acid with the formula HOOCCH(NH2)CH2C6H5. It is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. Tyr and Phe play a significant role not only in protein structure but also as important precursors for thyroid and adrenocortical hormones as well as in the synthesis of neurotransmitters such as dopamine and noradrenaline. The genetic disorder phenylketonuria (PKU) is the inability to metabolize Phe. This is caused by a deficiency of phenylalanine hydroxylase with the result that there is an accumulation of Phe in body fluids. Individuals with this disorder are known as phenylketonurics and must abstain from consumption of Phe. A nonfood source of Phe is the artificial sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester), which is metabolized by the body into several by-products including Phe. The side chain of Phe is immune from side reactions, but during catalytic hydrogenations the aromatic ring can be saturated and converted into a hexahydrophenylalanine residue. ... 

The crude diazo ketone (30.8-33.4 g) always contains about 10% of Boc-L-phenylalanine methyl ester formed by esterification of Boc-L-phenylalanine with diazomethane. This material can be carried through the synthesis and is removed during Step B. 

Thermolysine Syntheses of N-(benzyloxycarbonyl)-L-alanyl-L-phenylalanine methyl ester and N-(benzyloxycarbonyl)-L-aspartyl-phenylalanine methyl ester in HEPES or MES-NaOH buffers/ethyl acetate [74]... 

Proteases have been much less studied than lipases in ionic liquid media and generally require the presence of water for activity. We note that the thermolysin-catalyzed amide coupling of benzoxycarbonyl-L-aspartate and L-phenylalanine methyl ester into Z-aspartame in [BMIm][PF6] was an early example of an enzymatic reaction in an ionic liquid medium [8]. 

Aspartame. Aspartame [22839-47-0] [53906-69-1] (APM, L-aspartyl-L-phenylalanine methyl ester) (1), also known under the trade names of NutraSweet and EQUAL, is the most widely used nonnutritive sweetener worldwide. This dipeptide ester was synthesized as an intermediate for an antiulcer peptide at G. D. Searle in 1965. Although this compound was known in the literature, its sweet taste was serendipitously discovered when a chemist licked his finger which was contaminated with it. Many analogues, especially the more stable esters, were made (6) and their taste qualities and potencies determined. It was the first compound to be chosen for commercial development. Following the purchase of G. D. Searle by Monsanto, the aspartame business was split off to become a separate Monsanto subsidiary called the NutraSweet Company. 

In principle, aspartame is produced through the coupling of two amino acid moieties. One moiety consists of L-phenylalanine methyl ester hydrochloride (2) made by treating the amino acid in methanol and hydrochloric acid the other is aspartic acid anhydride hydrochloride or formic acid salt. The coupling reaction generates two positional isomers, a and p. 

The first member of this class of sweetners, L-aspartyl-L-phenylalanine methyl ester... 

L-Aspartyl-L-phenylalanine methyl ester (aspartame) (sweet)... 

No generalizations can be made about the molecular weights of biologically active peptides and proteins in relation to their functions. Naturally occurring peptides range in length from two to many thousands of amino acid residues. Even the smallest peptides can have biologically important effects. Consider the commercially synthesized dipeptide L-aspartyl-L-phenylalanine methyl ester, the artificial sweetener better known as aspartame or NutraSweet. 

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