Alanine amide

Alitame (trade name Adame) is a water-soluble, crystalline powder of high sweetness potency (2000X, 10% sucrose solution sweetness equivalence). The sweet taste is clean, and the time—intensity profile is similar to that of aspartame. Because it is a stericaHy hindered amide rather than an ester, ahtame is expected to be more stable than aspartame. At pH 2 to 4, the half-life of aUtame in solution is reported to be twice that of aspartame. The main decomposition pathways (Fig. 6) include conversion to the unsweet P-aspartic isomer (17) and hydrolysis to aspartic acid and alanine amide (96). No cyclization to diketopiperazine or hydrolysis of the alanine amide bond has been reported. AUtame-sweetened beverages, particularly colas, that have a pH below 4.0 can develop an off-flavor which can be avoided or minimized by the addition of edetic acid (EDTA) [60-00-4] (97). 

Chemical Name N-carboxy-/3-alanyl-L-tryptophyl-L-methionyl-L-aspartylphenyl-L-alanin-amide N-tert-butyl ester... 

A simple and rapid method of separating optical isomers of amino acids on a reversed-phase plate, without using impregnated plates or a chiral mobile phase, was described by Nagata et al. [27]. Amino acids were derivatized with /-fluoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA or Marfey s reagent). Each FDAA amino acid can be separated from the others by two-dimensional elution. Separation of L- and D-serine was achieved with 30% of acetonitrile solvent. The enantiomers of threonine, proline, and alanine were separated with 35% of acetonitrile solvent and those of methionine, valine, phenylalanine, and leucine with 40% of acetonitrile solvent. The spots were scraped off the plate after the... 

Van Alsenoy, C., M. Cao, S. Q. Newton, B. Teppen, A. Perczel, I. G. Csizmadia, F. A. Momany, and L. Schafer. 1993. Conformational Analysis and Structural Study by Ab Initio Gradient Geometry Optimizations of the Model Tripeptide N-formyl L-alanyl L-alanine Amide. J. Mol. Struct. (Theochem) 286,149-163. 

Schafer, L., I. S. Bin Drees, R. F. Frey, C. Van Alsenoy, and J. D. Ewbank. 1995c. Molecular Orbital Constrained Gas Electron Diffraction Study of N-Acetyl N -MEthyl Alanine Amide. J. Mol. Struct. (Theochem) 338, 71-82. 

Many of the conformational properties of peptide systems, including protein conformation, can be approximated in terms of the local interactions encountered in dipeptides, where the two torsional angles 4> (N-C(a)) and < i (C(a)-C ) are the main conformational variables. N-acetyl N -methyl alanine amide, shown in Fig. 7.11, is a model dipeptide that has been the subject of numerous computational studies. 

Fig. 7.11 N-acetyl N -methyl alanine amide. Identification of the 4> (N-C(a)) and i / (C(a)-C ) torsional angles.

Alitame, L-a-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alanine amide, has undergone a series of safety studies. While most of the studies did not show adverse effects and no indications for carcinogenicity were found, a dose-dependent increase in liver weights was found at levels above 100 mg/kg which was identified as the no-effect level. While JECFA has allocated an ADI of 0-1 mg/kg12 only a few countries, but neither the European Union nor the USA, have approved alitame. 

L-Alanine amide (S)-8 was converted to D-alanine (R)-9 in excellent yield and enantiomeric excess by incubation of the substrate with a-amino-e-caprolactam racemase from Achromohacter obae and D-aminopeptidase from Ochrobactrum anthropi (Scheme 2.5) [7]. 

Fig.2 The calculated 13C chemical shift map of the Cp carbon in N-acetyl-N -methyl-L-alanine amide obtaining using the FPT INDO method. The chemical shifts were calculated at 15° intervals for the dihedral angles(< >,i /).

Figure 1. LMO contributions to shielding for Ca in 7V-formyl-alanine amide as a function of ( ), / computed using the deMon program. The individual, sum of major, and overall contributions to shielding are shown.

Table I. Major LMO contributions to 13Ca isotropic shielding in V-formyl-glycine amide, V-formyl-alanine amide, V-formyl-valine amide, and V-formy 1-phenylalanine amide (deMon program, PW91, uniform IGLOII basis set)... 

Figure 4. Cp-Ca, Cp-Hp and total LMO contributions to Cp shielding in N-formyl-alanine amide as a function of 0 j/.

The NMR shieldings are calculated by ab initio GIAO-CHF method with the 6-31G basis set. N-acetyl-N -methyl-L-alanine amide (Ac-L-Ala-NH-Me)... 

Figure 1. Structure of N-acetyl-N -methyl-L-alanine amide used in NMR shielding calculations.

In one of the steps in the synthesis of thienopyridine metalloprotease inhibitors possessing anticancer and antiinflammatory activities, the pyridine ring is constructed by treating (3-(2-thienyl)-D-alanine (274) with formaline in an acidic medium (1998EUP803505, 1999PCT9906410). In particular, this method was used to prepare 6-(R)-amino acid 275 in 91% yield. AT-Cbz-(3-(2-Thienyl)-L-alanine amide 276 was transformed into 4,5,6,7-tetrahydrothienopyridine-(65f)-carboxamide by dimeth-oxymethane in the presence of an acid (1996USP5480887). Compound 277 serves as an intermediate in the synthesis of anti-AIDS drugs. 

A)-alcohol (7) by Sphingomonas paucimobilis SC 16113 (Fig. 6) (2) the enzymatic resolution of racemic (a-methyl)phenylalanine amide (8) and a-(4-methoxyphenyl)alanine amide (10) by amidase from Mycobacterium neoaurum ATCC 25795 to prepare the corresponding (S)-amino acids (9) and (11), and (3) the asymmetric hydrolysis of methyl-(4-methoxyphenyl)-propanedioic acid, diethyl ester (12), to the corresponding (X)-monoester (13) by pig liver esterase (Fig. 7). 

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