A-Methylglutamic acid

Gruszecka, E., Soroka, M., and Mastalerz, P, Phosphonic analogs of a-meth-ylaspartic and a-methylglutamic acids, Pol.. Chem., 53, 2327, 1979. 

Lamar C. 1970. Ammonia toxicity in rats Protection by a -methylglutamic acid. Toxicol Appl Pharmacol 17 795-803. 

Anfinsen.) DL-a-Methylglutamic acid was found to be active neither as a substrate nor as an inhibitor with the crystalline enzyme. ... 

When MLH had overcome the mentioned difficulties and some smaller ones, he synthesized the western building block 30 via p-ketothioester 34 as summarized in Scheme 8. The route toward diester 33 of L-A-methylglutamic acid, then not a known compound, started from commercially available Cbz-protected L-glutamic acid (73). Esterification with excess 2-(trimethylsilyl) ethan-l-ol ( TMSE-OH ), DCC, and DMAP furnished the diester 74 in 82% yield." It was methylated with Mel/Ag20 (—>93% 75 of 97-98% ee) adhering to a general procedure" and conscious of a specific application to a diester of... 

CgHiiNOi, 0.5 H2O, D,L-a-Methylglutamic acid hemihydrate, 45B, 511 CgHiiNOg, (2S,3R,4S)- -Hydroxy-a-methylglutamic acid, 40B, 442... 

Other Oxazolidine as well as Thiazolidine Derivatives for Branching Amino Acids. The cyclic derivative of alanine and other amino acids employed most frequently for a-allq lation is not (1) but rather the benzaldehyde acetal (5), either with a benzoyl or with a Cbz group on nitrogen. These compounds were used for the preparation of 2-methyl-2-aminobutanoic acid, a-methylphenylalanine, a-methyllysine, 2-methylaspartic acid, and 2-methylglutamic acid. Bicyclic compounds containing oxazolidinone rings such as (6) (from alanine, leucine, and phenylalanine) and (7) (from azetidinecaiboxylic acid, proline, " hydroxyproline, and cysteine ) have also been applied to the synthesis of branched amino acids. 

Other substances to which people have been exposed have been shown to alter the toxic effects of ammonia. Methionine sulfoximine, administered by intraperitoneal injection, suppressed the tonic convulsions produced by intravenous injection of ammonium chloride in mice (Hindfelt and Plum 1975 Warren and Schenker 1964). Intraperitoneal injection of alpha-methylglutamic acid also exerts a protective effect against hyperammonemia in rats (Lamar 1970). Nicotinohydroxamic acid and neomycin administered orally reduce blood ammonia levels and increase excretion of urea in treated rats (Haiada et al. 1985). Ethanol exerted a protective effect on acute ammonia intoxication in mice (O Connor et al. 

The enolatc of (2S,4R)-I can also undergo Michael addition to f-butyl acrylate. The yield is low, but the adduct is obtained in 98% ee. This reaction provides a route to a derivative of 2-methylglutamic acid (equation I). 

Subsequent to this work, apoaspartate transaminase was used to assay the stereospecificity of a variety of other transaminases, all of which were shown to involve protonation/deprotonation at the C-4 Si face of the cofactor. These enzymes included pyridoxamine-pyruvate transaminase (EC 2.6.1.30) (26) and a-dialkylamino acid transaminase (27). L-Glutamate decarboxylase (EC 4.1.1.15) catalyzes an abortive transamination reaction when oc-methylglutamate is used as substrate, and this too was shown to occur with protonation at the Si face of C-4 in the intermediate 4d (28) as was the abnormal transamination of D-alanine by serine hydroxymethyltransferase (29). 

In spite of their potential in synthesis, accounts of additions of hydrophosphoryl compounds to enamines are spread rather thinly throughout the literature. As a contribution towards the synthesis of methylaspartic acid and methylglutamic acid analogues, ethyl esters of phosphinic acids, (EtO)RP(0)H, were shown to add to ethyl 3-aminobut-2-... 

An example of the third type (novel pathway) is the production of ery A o-4-methylglutamic acid (9) from L-leucine (10) in Gleditisia triacanthos (honey locust, Fabaceae) and not from glutamic acid and SAM or from lysine as in many other plants (Fig. 13.4). 

D-Amino acids are frequently encountered in these bacterial constituents. The formation of D-a//othreonine can be explained by the action of racemases on the a-carbon atom of L-threonine 69), Similarly, d-fl//oisoleucine can be produced from L-isoleucine (70) (see for example peptidolipin NA or cerexin A). However, in two cases, L-a//othreonine and L-a//oisoleucine have been found no information is available on their biosynthesis. Unusual amino acids have also been observed in some of these peptidolipids, for instance pipecolic acid (amphomycin), L-threo- -hydroxyglutamic and L-t/ireo-P-methylglutamic acids (neopeptines), or D- or L- 2,4-diaminobutyric acid (octapeptines). 

Very mild treatment with alkali produced a ring-opened derivative, thus showing the presence of a lactone ring and allowing the release of P-methylglutamic acid by further treatment with carboxypeptidase. 

Of many non-protein amino acids known in plants, only a few have been found in ferns. Several unusual monoaminodicarboxylic acids have been obtained, mainly from the genus Asplenium. Fifteen New Zealand species of Asplenium contain (25,4i )-4-methyl-L-glu-tamic acid (848), (25)-4-hydroxy-4-methylglutamic acid (849) and 5-iV-acetyl-L-ornithine (844), but these were not detected in two Athyr-ium spp., A. australe and A. japonicum 499). This fact provides additional support for the proposal that there is no close affinity between the two genera Asplenium and Athyrium 499). 

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