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Upstream product

• 71-90-9 2-methylglutamic acid 
• 121704-30-1 N-Chloroacetyl-α-methylglutamic acid 
• 121704-31-2 N-Methoxyacetyl-α-methylglutamic acid 
• 160867-99-2 2-methylpyroglutamic acid 
• 151075-02-4 (+)-(2S)-Dimethyl 2-methyl-2-<(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl>pentane-1,5-dioate 
• 244127-80-8 (4S,8aS)-8a-methyl-4-phenyltetrahydro-pyrrolo[2,1c][1,4]oxazine-1,6-dione 
• 123-76-2 levulinic acid 
• 213619-68-2 (3S,6R)-N-1-(tert-butoxycarbonyl)-6-isopropyl-3-methyl-3-(2-methoxycarbonyl)ethyl-5-phenyl-1,2,3,6-tetrahydro-2-pyrazinone 
• 151074-88-3 (S)-2-Methyl-2-((S)-2-oxo-4-phenyl-oxazolidin-3-yl)-pentanedioic acid 

Relevant academic research and scientific papers

Synthesis of optically active, unnatural α-substituted glutamic acid derivatives by a chiral calcium-catalyzed 1,4-addition reaction

The first catalytic asymmetric 1,4-addition reactions of azlactones with acrylic esters have been developed. A chiral coordinative calcium catalyst was found to be effective for these reactions, and the desired 1,4-adducts were obtained in good yields and enantioselectivities. The product was converted to the corresponding α-alkylated glutamic acid by acid hydrolysis.

Asymmetric Strecker reaction of γ-keto acids. Facile entry to α-substituted and α,γ-disubstituted glutamic acids

The Strecker reaction of γ-keto acid derived sodium salts with (S)-phenylglycinol followed by treatment of the resultant α-amino nitriles with methanolic HCl and heating at 200°C give bicyclic lactones 11 and 12. Hydrolysis and subsequent debenzylation of

Asymmetric synthesis of α-Methyl α-Amino Acids through diastereoselective alkylation under mild reaction conditions of an iminic alanine template with a 1,2,3,6-Tetrahydro-2-Pyrazinone structure

(6R)-6-Isopropyl-3-methyl-5-phenyl-1,2,3,6-tetrahydro-2-pyrazinone, obtained from (R)-valine and (S)-alanine, is highly diastereoselectively alkylated at room temperature by: a) activated alkyl halides under solid-liquid PTC conditions, b) non-activated alkyl halides with organic bases, c) electrophilic olefins employing both solid-liquid PTC conditions and organic bases, and d) allylic carbonates by means of palladium catalysis under neutral conditions. Enantiomerically pure (S)-α-methyl α-amino acids 8 are obtained by hydrolysis of the alkylated pyrazinones.

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.

New chiral alanine template with a 1,2,3,6-tetrahydro-2-pyrazinone structure for the asymmetric synthesis of α-methyl α-amino acids

(R)-6-Isopropyl-5-phenyl- 1,2,3,6-tetrahydro-2-pyrazinone, prepared from (R)-valine and (S)-alanine, reacts With activated alkyl halides and electrophilic olefins under solid-liquid PTC conditions: with K2CO3 as base, at room temperature and with high diastereoselectivity (>94%). The palladium-catalyzed allylation reaction of this alanine derivative under neutral conditions at room temperature also takes place with a de>96%. Final hydrolysis of alkylated pyrazinones affords enantiomerically pure α-methyl α-amino acids.

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.

Asymmetric Synthesis of α-Alkyl-α-amino Acids from Chromium-Carbene-Complex-Derived β-Lactams

Optically active bicyclic β-lactam 3 was synthesized by photolysis of optically active oxazolidine carbene chromium complex 1 with oxazine 2.Conversion of the oxazolidine to the oxazolidinone gave a bicyclic β-lactam readily α-alkylated.Cleavage of the alkylated β-lactam gave optically active ester aldehyde 7, which was converted to a number of optically active α-alkyl-α-amino acids.These include (R)-α-methylserine, (S)-α-methylglutamic acid, (S)-α-methylornithine, (S)-vinylalanine, (S)-ethynylalanine, and (S)-2-methyl-2,3-diaminopropionic acid.

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.