L-Aspartyl-D-phenylalanine methyl ester

A sweetener must be soluble in water and the molecule must bind readily to a specific kind of receptor molecule at the surface of the tongue. The receptor is coupled to a G-protein, which dissociates when the sweetener binds to the receptor, activating a nearby enzyme, and triggering a sequence of events resulting in signals that are carried to and interpreted by the brain. The sweetness signal depends on this interaction between receptor and sweetener. The importance of molecular shape to sweemess is illustrated by the case of aspartame, as its stereo isomer, L-aspartyl-D-phenylalanine methyl ester, has a bitter, not a sweet, taste. 

L-Aspartyl-L-phenylalanine Methyl Ester D-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). 

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. 

Aspartame is the generic name for IV-ai-aspartyl-L-phenylalanine methyl ester. It is composed of two amino acids, L-aspartic acid and L-phenylalanine, joined by a methyl ester link. It was discovered in 1965 by J. Schlatter at the G.D. Searle Laboratories. It is a white crystalline product and its solubility in water is 10 g/1 at 20°C this figure increases at elevated temperatures and in acidic conditions (Ajinomoto Aspartame Technical Bulletin, 2003). It is sparingly soluble in other solvents. 

Aspartame. Aspartame is a high-intensity sweetener (200-fold that of sucrose) consisting of L-aspartyl-L-phenylalanine methyl ester (L-Asp-L-Phe-OMe). Around 10,000 tons are produced per annum, most by a chemical process owned by Nutrasweet Corp. Holland Sweetener Company (a DSM/Tosoh joint venture) uses the protease thermolysin (E.C. 3.4.24.27) to synthesize aspartame from a chemically protected L-aspartic acid derivative (Z-L-Asp) and racemic phenylalanine methyl ester (DL-Phe-OMe). The enzyme only accepts L-phenylalanine-OMe and the unused D-isomer can be isolated, racemized, and recycled. This process is depicted in Figure 31.20. 

A number of synthetic peptides are significant commercial products, ranging from the sweet dipeptide aspartame (L-aspartyl-L-phenylalanine methyl ester) to clinically used hormones such as insulin and oxytocin. L-Aspartyl-L-phenylalanine methyl ester (3 Scheme 2) is the methyl ester of the C-terminal dipeptide of gastrin. It was found accidently during the synthesis of gastrin that this synthetic sweetener is about 200 times as sweet as sucrose.f This pleasant sweetness without a bitter aftertaste was the reason that L-aspartyl-L-phenylalanine methyl ester was approved in many countries as a food additive, receiving much attention as a low-calorie sweetener. L-Aspartyl-L-phenylalanine methyl ester can be prepared by various chemical routes and the first enzymatic procedure of commercial interest was described by Isowa et al.h l In the industrial process,L-Asp and DL-Phe were chosen as inexpensive raw materials. L-Asp is available very inexpensively, whereas L-Phe is more expensive than DL-Phe. Z-D-Asp acts as a competitive inhibitor, while D-Phe-OMe... 

Amino-N-(a-methoxycarbonylphenethyl) succinamic acid 3-Amino-N-(a-carboxyphenethyl)succinamic acid N-methyl ester APM Asp-phe-ome Aspartam Aspartame Aspartame, L,L-a- Aspartamo Aspartamum Aspartylphenylalanine methyl ester L-Aspartyl-L-phenylalanine methyl ester Canderel CCRiS 5456 DIpeptide sweetener EINECS 245-261-3 Equal HSDB 3915 Methyl aspartylphenylalanate Methyl L-aspartyl-L-phenylalanine Methyl L-a-aspartyl-L-phenylalanate Methyl N-L-a-aspartyl-L-phenylalaninate 1-Methyl N-L-a-aspartyl-L-phenylalanate Nutrasweet L-Phenylalanine, L-a-aspartyl-, 2-methyl ester L-Phenylalanine, N-L-a-aspartyl-, 1-methyl ester SC 18862 Succinamic acid, 3-amino-N-(a-carboxyphenethyl)-, N-methyl ester, Sweet dipeptide Tri-sweet, A sweetening agent Crystals mp = 246-247° [a]8 = -2,3° (IN HCI). Searte 6.D. Co. 

Aspartame was discovered accidentally in 1965 by James M. Schlatter, an employee of the G. D. Searle pharmaceutical company. Schlatter was searching for a chemical compound that could be used to treat ulcers. L-aspartyl-L-phenylalanine methyl ester was one of the compounds he made during his investigations. He accidentally got some of the compound on his fingers, a fact that he did not notice until later in the day. 

Therefore racemization 1s in the same range as that observed for the racemizatlon-resistant azide procedure. The coupling of Cbz-L-aspartyl(O-t-Bul-L-phenylalanine with valine methyl ester is reported to be very sensitive to racemization.14 The trlpeptlde was prepared as described above, and the crude product was hydrolyzed. GLC showed the presence of 2-3% D-... 

Aspartame (a-L-aspartyl-L-phenylalanine 1-methyl ester) is a sweetening agent that is roughly 200 times sweeter than sucrose. Routes for preparing this compound are described in U.S. 3,492,131, U.S. 4,440,677 (both to G. D. Searle Co.), and U.S. 5,476,961 (to the NutraSweet Company). Determine which route gives the lowest cost of production. 

In human nutrition, free amino acids play an important role in aromatisa-tion, as flavour enhancers, and as sweeteners. Monosodium glutamate, in concentrations of 0.1-0.4%, is probably the most prominent flavour enhancer for spices, soups, sauces, meat and fish. (L)-Cysteine amplifies the flavour of onions. Glycine is used to mask the aftertaste of saccharin. Whereas (L)-amino acids may taste slightly bitter, the (D)-enantiomers have a sweet taste. This is in general also true for the corresponding di- and oligopeptides - except for the methyl ester of (L)-aspartyl-(L)-phenylalanine (Aspartame). 

Aspartame was discovered by accident by Jim Schlatter, a chemist at G.D. Searle in 1965. Jim Schlatter was working on drugs for the treatment of gastric ulcers when he spilled some aspartyl-phenylalanine on his hand. He later licked his finger and noticed the sweet taste of the compound, which later became aspartame. Aspartame is the methyl ester of the dipeptide of the natural amino acids L-aspartic acid and L-phenylalanine. There are four possible diastereoiso-mers for aspartame but aspartame is the only one having sweetening properties. The taste of aspartame would not have been predictable based on its amino acid constituents. 

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