D-Alanine amide

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-a-Aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-D-alanin-amide anhydrous [80863-62-3]... 

Asano et al. have also purified a D-stereospecific amino acid amidase from another Ochrobadrum anthropi isolate137, 38i. Recently, a new amidase from Comamonas acidovorans has been reported that exhibits a broad substrate specificity and also d-amino acid amidase activity1391. In addition, a D-specific amidase has been identified in Arthrobacter sp. NJ-261401. In contrast to the D-selective enzymes of Ochrobadrum sp. and Comomonas acidovorans, the D-amide hydrolase identified in Arthrobacter sp. NJ-26 was very substrate specific a good hydrolysis rate was only observed for d-alanine amide. 

In some peptidoglycans, the a-carboxyl function of the D-glutamyl residue is substituted with glycine (M. lysodeikticus), glycine amide A. arthrocyaneus), or D-alanine amide Arthrobacter sp.). The corresponding N-acetyl-muramyl-tripeptides (56—58), have been synthesized 32, 44, 4S). 

Like aspartame, alitame also undergoes a/P-rearrangement. Both isomers hydrolyze slowly to give L-aspartic acid and D-alanine amide, which is excreted either directly or as the glucuronide. A small part is oxidized to sulfoxides and sulfone. Cyclization to diketopiperazine which is typical of dipeptide methylesters does not occur. 

Like aspartame and neotame, alitame (in some countries known as aclame, 11-26), L-a-aspartyl-JV-(2,2,4,4-tetramethyl-3-thietanyl)-D-alanine amide, is an aspartic acid-based dipeptide, which is about ten times sweeter than aspartame and has no after-taste. As with aspartame, it is hydrolysed in acidic media, but does not contain bound phenylalanine and can therefore be used by people with phenylketonuria. Alitame is not approved for use in the EU or the USA, but is approved in Australia, China and some other countries. 

Production of o-alanine from L-alanine amide by DAP in the presence of ACL racemase. (o), D-alanine amide ( ), i-alanine amide ( ), o-alanine. 

D-alanine (peptides) DL-alanine (peptide) amide(s) D-amino acid arninopeptidase Ochrobactrum anthropi, Bhodococcus erythropolis 174... 

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... 

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. 

Chiral rra s-2,5-dialkylpyrrolidines, which were used for the synthesis of ant-venom pyrrolizidines, were prepared in the following manner, d-Alanine was transformed into an pentenylamine which, upon intramolecular amidomercuration, yielded 15 (90TA561 92JOC4401). From a protected AA amide, after a Grignard reaction and treatment of the aminoketone with ethyl acetoacetate, the tetrasubstituted pyrrole 16 was obtained [93H(35)843],... 

At the Start of the cross-linking process, the peptide chains from the A -acetylmuramic acid residues have a terminal -Lys-o-Ala-o-Ala sequence. The lysine from one chain then becomes bonded to the penultimate d-alanine of another chain through five glycine residues, at the same time displacing the terminal o-alanine. The mechanism involves a serine residue at the active site of the enzyme. This residue is used to convert an amide linkage into an ester, and a reversal of this sequence provides the new peptide bond. 

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]. 

The fatty acid chains are evidently embedded in the outer membrane as an anchor. About one-third of the lipoprotein molecules are attached covalently to the peptidoglycan through an amide linkage between the side chain amino group of the C-terminal lysine of the protein and a diaminopimelic acid residue of the peptidoglycan (Fig. 8-29). Thus, the protein replaces one of the terminal D-alanine residues of about one in ten of the murein peptides. There are 2.5 x 105 molecules of the bound form of the lipoprotein per cell spread over a surface area of peptidoglycan of 3 pm2. They appear to be associated as trimers located primarily in the periplasmic space.589... 

Stabilization is maintained by several hydrogen bonds. Interesting details include a single m-amide linkage between MeLeu-9 and MeLeu-10. Furthermore, the L-configuration of MeBmt-1 was confirmed and the still unknown partial sequence of residues 7 and 8 was determined as L-alanine-D-alanine. The absolute configuration of iodocyclosporin A and hence that of cyclosporin A were deduced from the reliable identification of the L-amino-acid residues. 

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. 

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