4493-08-7

Basic information

• Product Name: (R)-α-Methylglutamic acid
• CAS NO: 4493-08-7
• Molecular Weight: 161.158
• Mol File: 4493-08-7.mol

Chemical Properties

• CAS DataBase Reference: (R)-α-Methylglutamic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-α-Methylglutamic acid(4493-08-7)
• EPA Substance Registry System: (R)-α-Methylglutamic acid(4493-08-7)

Safety Data

• Hazardous Substances Data: 4493-08-7(Hazardous Substances Data)

Upstream product

• 71-90-9 2-methylglutamic acid 
• 1354568-59-4 (S)-3-allyl-1-benzoyl-3-methylpiperidine-2,6-dione 
• 185054-65-3 (R)-5-Hydroxy-2-methyl-2-nitro-pentanoic acid tert-butyl ester 
• 185054-66-4 (R)-4-(tert-butoxycarbonyl)-4-nitropentanoic acid 

Relevant articles and documents

Enantioselective allylation of nitro group-stabilized carbanions catalyzed by chiral crown ether phosphine-palladium complexes

Enantioselective allylations of α-nitro ketones (3) and α-nitro esters (15) with allyl acetate were carried out in the presence of 2 equiv of alkali metal fluorides (KF, RbF, CsF) and 1 mol % of palladium catalysts prepared in situ from Pd2(dba)3·CHCl3 and chiral phosphine ligands. Moderate enantioselectivities were observed in the reaction of nitro ketones 3, giving products 4 (4a, 49% ee; 4b, 58% ee; 4c, 44% ee) when rubidium fluoride and ferrocenylphosphine ligands bearing monoaza-15-crown-5 (1b) or monoaza-18-crown-6 (1c) moieties were used as a base and a chiral ligand, respectively. Optically active allylation product 4a was converted into 1-methyl-1-azaspiro[4.5]-decan-10-amine (13), a precursor to opioid receptor binding agents. Enantioselectivity in the reaction of nitro esters 15 increased in accord with increasing steric demand of the ester alkyl group (Me 4 (1 equiv). The pronounced effect of the crown ether moiety for both enantioselection and rate acceleration can be explained by assuming the formation of a ternary complex involving the crown ether, rubidium cation, and enolate anion at the stereodifferentiating transition state. Optically active nitro ester (R)-16c was converted into (R)-α-methylglutamic acid (20).

Sequential ruthenium catalysis for olefin isomerization and oxidation: Application to the synthesis of unusual amino acids

How can you use a ruthenium isomerization catalyst twice? A ruthenium-catalyzed sequence for the formal two-carbon scission of allyl groups to carboxylic acids has been developed. The reaction includes an initial isomerization step using commercially available ruthenium catalysts followed by in situ transformation of the complex to a metal-oxo species, which is capable of catalyzing subsequent oxidation reactions. The method enables enantioselective syntheses of challenging α-tri- and tetrasubstituted α-amino acids including an expedient total synthesis of the antiepileptic drug levetiracetam.

Chiral 3,6-dihydro-2H-1,4-oxazin-2-ones as alanine equivalents for the asymmetric synthesis of α-methyl α-amino acids (AMAAs) under mild reaction conditions

3,6-Dihydro-2H-1,4-oxazin-2-ones 1 act as very reactive chiral cyclic alanine equivalents and can be diastereoselectively alkylated or allylated using mild reaction conditions: potassium carbonate under phase-transfer catalysis (PTC) conditions when using activated alkyl halides, organic bases such as tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2- diazaphosphorine (BEMP) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) when using unactivated alkyl halides, and neutral Pd(0)-catalysis when allylic carbonates are used. In most cases, the diastereoselectivity under all these different reaction conditions is excellent although the reactions are always carried out at room temperature. Hydrolysis of the obtained alkylated or allylated oxazinones allows the preparation of enantiomerically enriched (S)- α-methyl α-amino acids (S)-AMAAs. The PTC and organic base methodologies have also been applied to the synthesis of (R)-α-methyl α-amino acids starting from (R)-alanine. When dihalides are used as electrophiles under PTC or BEMP conditions, a spontaneous N-alkylation also takes place giving bicyclic oxazinones, which can be hydrolyzed to enantiomerically pure cyclic (S)-AMAAs.

Asymmetric synthesis of α-methyl α-amino acids by diastereoselective alkylation of optically active 6-isopropyl-3-methyl-2,3-dihydro-6H-1,4-oxazin-2-ones

At room temperature already highly diastereoselective alkylation of the new, cyclic, chiral alanine ester derivatives (6R)-1 can be achieved with either K2CO3 as base under solid liquid phase-transfer catalysis or Pd catalysis under neutral conditions. The products (3S,6R)-2 can be easily hydrolyzed to form (S)-α-methyl α-amino acids.

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.

Resolution and regioselective protection of glutamic acid analogues. I- Resolution of diastereomeric α-boroxazolidone derivatives

Diastereomeric α-boroxazolidone γ-phenylethylamide (or γ-phenylethanolamide) derivatives of 2-, 3- or 4-substituted glutamic acid analogues have been separated by silicagel chromatography, resulting, after deprotection, in a practical method for the resolution of most of these unnatural amino acids.

A NOVEL APPLICATION OF THE CHIRAL REAGENT (S)-2-N-(N'-BENZYLPROLYL)-AMINOBENZALDEHYDE: SYNTHESIS OF OPTICALLY PURE α-METHYLVALINE AND α-METHYLGLUTAMIC ACID

The synthesis of α-methyl substituted amino acids using Ni(II) complexes of the Schiff base obtained from alanine and (S)-2-N-(N'-benzylpropyl)aminobenzaldehyde is described.This complex was alkylated with isopropyl bromide, gramine iodomethylate, and methyl acrylate (in a Michael reaction).From the resulting mixtures of products, diastereomerically pure complexes were obtained by crystallization or silica gel chromatography.Both (S)- and (R)-enantiomers of the optically active amino acids α-Me-Val and α-MeGlu were obtained after decomposing the diastereomerically pure complexes.