Α-methylaspartic Acid Research Articles

ChemInform Abstract: Synthesis of (S)-α-Methylaspartic Acid by Diastereoselective Alkylation of a Chiral 2-Cyanopropanoate.

ChemInform Abstract: Synthesis of (S)-α-Methylaspartic Acid by Diastereoselective Alkylation of a Chiral 2-Cyanopropanoate.

Enantiomerically Pure Tetrahydropyrimidinones in Asymmetric Synthesis: Preparation of a Protected α-Methylasparagine Derivative and Corresponding Dipeptides

Methyl ester 5a, available in enantiomerically pure form from the amino acid asparagine via a one-pot cyclization/protection sequence, followed by esterification, can be effectively deprotonated with LDA/DMPU/LiCl. Treatment with MeI affords the corresponding alkylated adduct in enantiomerically pure form, from which α-methylaspartic acid is obtained. Variation of the amine protection group allows for the isolation of a protected carboxylic acid/free amine derivative of α-methylasparagine. The utility of H-MeAsn-OMe is demonstrated in the formation of dipeptides.

Probing the Role of an Active Site Aspartic Acid in Dihydrofolate Reductase

Analogues of E. coli dihydrofolate reductase (DHFR) containing modified amino acids at single, predetermined sites have been prepared. This was accomplished by the use of the DHFR gene containing an engineered nonsense codon (TAG) at the positions corresponding to Val-10 and Asp-27. Misacylated suppressor tRNAs activated with the modified amino acids of interest were employed for the suppression of the nonsense codons in a cell free protein biosynthesizing system, thereby permitting the elaboration of the desired protein analogues. In this fashion, the aspartic acid analogues erythro-carboxyproline, cysteic acid, β,β-dimethylaspartic acid, α-methylaspartic acid, erythro- and threo-β-methylaspartic acid, N-methylaspartic acid, and phosphonoalanine were incorporated into one or both of the aformentioned positions. Although a number of these analogues were incorporated only in low yield, a modification of the strategy has suggested how this might be improved significantly. The derived proteins were purified and then characterized by their mobility on polyacrylamide gels in comparison with wild-type DHFR. Representative DHFRs modified at position 10 were also degraded by defined proteolysis with Glu-C endoproteinase; the fragments containing the modified amino acids were shown to have the same chromatographic properties on reverse phase HPLC as authentic synthetic standards. Individual analogues were assayed for their abilities to bind to the substrate analogue methotrexate and to convert dihydrofolate to tetrahydrofolate. DHFR analogues containing erythro- and threo-β-methylaspartic acid and β,β-dimethylaspartic acid were all shown to mediate tetrahydrofolate production 74−86% as efficiently as wild-type DHFR under conditions of multiple substrate turnover. Analysis of the rates of tetrahydrofolate production in the presence of NADPH and NADPD at two pH values suggests that this was due to rate-limiting hydride transfer from NADPH bound to DHFR analogues whose active site had been altered structurally.

On the synthesis of (S)-α-methylaspartic acid by diastereoselective alkylation of a chiral 2-cyanopropanoate

Abstract A novel and efficient procedure for the synthesis of optically pure α-methylaspartic acid, based on the diastereoselective alkylation of (1 S ,2 R ,4 R )-10-(dicyclohexylsulfamoyl)isobornyl 2-cyanopropanoate with α-halocarbonyl compounds, is described.

A novel synthesis of ( R)- and ( S)-α-alkylated aspartic and glutamic acids: α-alkylated aspartic succinimides as new type of β-turn type II and II′ mimetics

A novel and efficient synthesis of optically pure ( R)- and ( S)-α-methyl glutamic acid ( 1), ( R)- and ( S)-α-methyl aspartic acid ( 2a) and ( R)- and ( S)-α-isobutyl aspartic acid ( 2b) using L-phenylalanine cyclohexylamide 4 as chiral auxiliary is described. Crystal structures show that the ( R)- and ( S)-α-methyl glutamic acid derivatives ( S,S)- 5 and ( R,S)- 6 adopt β-turn type I geometries, whereas the corresponding aspartimide derivatives ( R,S)- 12a,b form a β-turn type II and ( S,S)- 11a a β-turn type II′. These findings suggest, that the succinimide derivatives of ( R)- and ( S)-α-alkyl aspartic acids can serve as building blocks to stabilise β-turns of type II (or II′) in peptides depending on their absolute configuration.

Enantiospecific synthesis of amino acids: preparation of ( R)- and ( S)-α-methylaspartic acid from ( S)-tryptophan

The enantiospecific synthesis of both antipodes of α-methylaspartic acid from ( S)-tryptophan is described with the key steps being alkylation of the hexahydropyrroloindole 4, oxidative degradation of indoles and, for the preparation of the ( R)-isomer, Barton reductive decarboxylation. The enantiomeric α-methylaspartic acid hydrochlorides ( 1) and ( 2) were prepared, separately, from ( S)-trytophan via its tautomeric hexahydro[2,3b]pyrroloindole derivative ( 3).

Asymmetric synthesis of aspartic and ?-methylaspartic acids via Ni(II) complexes with schiff bases of glycine and alanine and chiral carbonyl-containing reagents

We propose a method for the synthesis of aspartic and α-methylaspartic acids by alkylation with ethyl bromoacetate of the α-carbon atom of the amino acid moiety in Ni(II) complexes of Schiff bases of glycine with (S)-2-[(N-benzylprolyl)amino]benzophenone and alanine with (S)-2-[(N-benzylprolyl)amino]-benzaldehyde, respectively. Attempts to synthesize α-methylaspartic acid by oxidative cleavage of the C=C bond to a COOH group in the complex of the Schiff base of α-allylalanine with (S)-2-[(N-benzylprolyl)amino]benzophenone were unsuccessful.

Phosphinic Acid analogues of methylaspartic and methylglutamic acids as antibacterials.

DL-l-Amino-l-methyl-3-carboxypropanephosphinic acid, a bioisostere of α-methylglutamic acid, was synthesized. This compound, the corresponding α-methylaspartic acid analogue and their precursors were tested for antibacterial activity. The methylaspartic acid analogue gave a MIC of 400 and 800 µg/ml against B. subtilis and P. aeroginosa, respectively.

Excitatory Amino Acid Receptor Interactions of a Novel α-Phosphinic Acid Analogue of α-Methylaspartic Acid

An α-phosphino analogue of α-methylaspartate has been synthesized. The compound may not interact with excitatory amino acid receptors directly, as assessed by direct in vitro radioreceptor binding methods; however, it possesses weak anticonvulsant activity and exhibits an excitant action in vitro that is apparently not mediated by a N-methyl-D-aspartate receptor.

Polycondensation of thermal precursors of amino acids and characterization of constituent amino acids

As a model reaction of polyamino acid formation from non-amino acid precursors, diammonium citraconate (I), ammonium citraconamate(II) and ammonium itaconamate(III) were converted to polyimide type polymers by thermal polycondensation by heating at 130–210°C. The imide type polymer was partially hydrolyzed to the corresponding peptide type polyamino acid. The polymer was composed of α-methylaspartic acid (IV), threo- and erythro-ß-methylaspartic acid (V) and α-(aminomethyl) succinic acid (VI). On the other hand, IV was thermally polycondensed to the corresponding polymer. It was found that the amino acid composition of the polymer was similar to that of the polymer prepared from I, II and III. The formation and isomerization of amino acids during the thermal polycondensation are described.

The interaction of aspartate aminotransferase with alpha-methylaspartic acid.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Interaction of Aspartate Aminotransferase with α-Methylaspartic Acid*Paolo Fasella, Anna Giartosio, and Gordon G. HammesCite this: Biochemistry 1966, 5, 1, 197–202Publication Date (Print):January 1, 1966Publication History Published online1 May 2002Published inissue 1 January 1966https://doi.org/10.1021/bi00865a026RIGHTS & PERMISSIONSArticle Views80Altmetric-Citations85LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (485 KB) Get e-Alerts Get e-Alerts

Studies on Optically Active Amino Acids. XI. Studies on α-Alkyl-α-amino Acids. VI. Chemical Correlation of Absolute configuration of α-Methylphenylalanine to α-Methylaspartic Acid

The absolute configuration of (+)-α-methylphenylalanine hydrochloride has been elucidated to be either R- or d-configuration by the chemical correlation with (-)-α-methylaspartic acid, whose absolute configuration had been cofirmed to be R-configuration. The resolution of N-acetyl-DL-α-methylphenylalanine through its menthyl esters was also reported.

Studies on Optically Active Amino Acids. IX. Studies on α-Alkyl-α-amino Acids. IV. Chemical Correlation of Absolute Configuration of α-Methylaspartic Acid to Isovaline

The absolute configuration of (+)-α-methylaspartic acid has been established to be S-configuration by the chemical correlation with (+)-isovaline, which was already correlated to D-(-)-quinic acid. The Chemical scheme employed was shown in Chart 1. Preliminary examinations using racemic compounds were also reported.