2-Aminobutyric acid, alkylation

A similar pathway involving a microwave-driven molybdenum-catalyzed asymmetric allylic alkylation as the key step was elaborated by Moberg and coworkers for the preparation of the muscle relaxant (R)-baclofen (Scheme 6.52) [108]. The racemic form of baclofen is used as a muscle relaxant (antispasmodic) lipophilic derivative of y-aminobutyric acid (GABA). Pharmacological studies have shown that the (R)-enantiomer is the therapeutically useful agonist of the GABAb receptor. Asymmetric alkylation of the allylic carbonate precursor with dimethyl malonate afforded... 

The aforementioned polymer-supported bis-pyridyl ligand has also been applied in microwave-assisted asymmetric allylic alkylation [140], a key step in the enantio-selective synthesis of (R)-baclofen (Scheme 7.118), as reported by Moberg and coworkers. The ( (-enantiomer is a useful agonist of the GABAb (y-aminobutyric acid) receptor, and the racemic form is used as a muscle relaxant (antispasmodic). Under microwave heating, the enantioselectivity could be improved to 89% when using toluene as solvent (see also Scheme 6.52) [140],... 

White, H. S., Sarup, A., Bolvig, T., et al. (2002) Correlation between anticonvulsant activity and inhibitory action on glial gamma-aminobutyric acid uptake of the highly selective mouse gamma-aminobutyric acid transporter 1 inhibitor 3-hydroxy-4-amino-4,5,6,7-tetrahydro-l,2-benzisoxazole and its N-alkylated analogs. J. Pharmacol. Exp. Ther. 302, 636-644. 

A variety of methods exists for the synthesis of optically active amino acids including asymmetric synthesis92-100 and classic and enzymatic resolutions.101-104 However, most of these methods are not readily applicable to the preparation of a,a-disubstituted amino acids as a result of poor stereoselectivity and lower activity at the a-carbon. Attempts to resolve the racemic 2-amino-2-ethylhexanoic acid and its ester through classic resolution failed. Several approaches for the asymmetric synthesis of the amino acid were evaluated including alkylation of 2-aminobutyric acid... 

The 1-phenylpyrazole core has been shown to bestow pharmacological activity in a number of areas in the pharmaceutical and agrochemical industries. In the latter field, select examples of biological activities include insecticidal, miticidal, and herbicidal. More specifically, 1-phenylpyrazoles with alkyl, acyl, thioalkyl, or cyano substituents at the 4-position exhibit potent insecticidal activity. In particular, 5-amino-I-(2,6-dichloro-4-trifluoro-methylphenyl)-4-trifluoromethanesulfinyl-l//-pyrazole-3-carbonitrile (Fipronil ) is one of the most commercially successful insecticides. In fleas, ticks, and other arthropods, it acts as a gamma-aminobutyric acid (GABA)-gated... 

A variety of methods exists for the synthesis of optically active amino acids, including asymmetric synthesis [85-93] and classic and enzymatic resolutions [94-97], However, most of these methods are not applicable to the preparation of a,a-disubstituted amino acids due to poor stereoselectivity and lower activity at the a-carbon. Attempts to resolve the racemic 2-amino-2-ethylhexanoic acid and its ester through classic resolution failed. Several approaches for the asymmetric synthesis of the amino acid were evaluated, including alkylation of 2-aminobutyric acid using a camphor-based chiral auxiliary and chiral phase-transfer catalyst. A process based on Schollkopf s asymmetric synthesis was developed (Scheme 12) [98]. Formation of piperazinone 24 through dimerization of methyl (5 )-(+)-2-aminobutyrate (25) was followed by enolization and methylation to give (35.6S)-2,5-dimethoxy-3,6-diethyl-3.6-dihydropyrazine (26) (Scheme 12). This dihydropyrazine intermediate is unstable in air and can be oxidized by oxygen to pyrazine 27, which has been isolated as a major impurity. 

Operating carefully under nitrogen, compound 26 was used as a template for diastereoselective alkylation with a series of alkyl bromides to produce derivatives 28, which were then hydrolyzed by strong acid to afford the dialky lated (A)-amino acids 29 (—90% ee), together with partially racemized 2-aminobutyric acid, which was separated from the product by ion-exchange chromatography (Scheme 13). This process provided gram quantities of the desired amino acids as analytical markers and test samples, but was not practical or economical for... 

Adding to the uncertainty over the existence of ethylmethoxypyrazine is that if the biosynthesis of methoxypyrazines in vines follows a previously postulated pathway (i), in which an amino acid is the source of the alkyl side chain, as already identified in bacteria by the incorporation of valine (22) or pyruvate (23) into isopropylmethoxypyrazine, then the biosynthesis of ethylmethoxypyrazine would require 2-aminobutyric acid, an amino acid not normally found in proteins, although it does exist in grapes and vegetables. 

CAS 68649-05-8 EINECS/ELINCS 272-021-5 Synonyms 3-Aminobutanoic acid, n-coco alkyl derivs. Butanoic acid, 3-amino-, N-coco alkyl derivs. N-Coco-3-aminobutyric acid Classification Substituted amino acid Formula R-NH-CFICFI2COOFICH3, R represents the coconut radical Properties FILB 13.6 amphoteric Toxicology TSCA listed... 

Because of the different and low stability of the isoindoles obtained from the reaction of AAs with OPA/MCE reagent, alternative precolumn derivat-izations reagents, such as 3-mercaptopropionic acid (MPA) and several N-alkyl-L/o-cysteines, were proposed. The OPA/MPA and OPA/N-acetyl-L-cysteine (NAC) reagents provide more stable isoindoles compared to those formed with the OPA/MCE, and the optical resolution of enantiomeric AAs with the OPA/NAC, as well as with further N-alkyl-L/o-cysteine reagents, have opened a new area in separation of AA enantiomers. Due to robotic autosamplers, which provide excellent reproducibility even for moderately quantitative interactions, most AA analyses are performed with the OPA derivative. The unexplainable contradictions of this most popular process - relating to the particularly low stability of the OPA derivatives of six very important AAs (glycine, y-aminobutyric acid (GABA), jS-alanine,... 

Rotational studies extended to non-coded a-amino acids are also of biochemical relevance [154]. The effects on the conformatimial behavior of enlarging the amino acid backbone chain have been analyzed on p-alanine [155, 156] and y-amino butyric acid (GABA) [157], Both are neurotransmitters which bind to the same sites as glycine [158—160], These are also the simplest p-amino and y-amino acids and so are the natural starting point to analyze the cmiformational panorama of this type of amino acids. Other studies include a-aminobutyric acid [161], the A(-alkylated species sarcosine [162], Af,Af-dimethylglycine [163], and taurine [164]. Brief results on p-alanine and GABA are presented. 

The Schiff s base derived from ethyl glycinate and benzophenone has been alkylated under both anhydrous and phase transfer conditions yielding, after hydrolysis, a-amino acids. Under phase transfer conditions, alanine, a-aminobutyric acid, valine, leucine and phenylalanine were prepared in 91%, 86%, 61%, and 55% yields, based on starting imine. 

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