Methylaspartate methylaspartic acid

Pip = D-pipecolic acid MeAsp = A -methylaspartic acid. The amphomycin family member having (+)-3-anteisotridecenoic acid is shown not shown is... 

Nodularia spwnigena has also been shown to produce a peptide with hepato-toxic activity. The more recent reports come from Australia (76), the German Democratic Republic (77), Denmark (78), Sweden (79), and Finland (80,81). Recently structure information on Nodularia toxin has been presented by Rinehart (97) for waterbloom material collected in Lake Forsythe, New Zealand, in 1984 by Eriksson et al. (81) from waterbloom material collected in the Baltic Sea in 1986, and Runnegar et al. (82) for a field isolate from the Peel Inlet, Perth, Australia. Structure work by Rinehart, Eriksson, and Runnegar all indicate that the peptide is smaller than the heptapeptide toxins. Rinehart s work (97) indicates the toxin is a pentapeptide with a similar structure to the heptapeptides and containing fi-methylaspartic acid, glutamic acid, arginine, dehydrobutyrine, and ADDA (MW 824). 

One substance that has been found to be an essential requirement for the biosynthesis of DNA is the cobalt-containing vitamin B12 (42). Ever since this substance was first isolated and its structure determined, there has been a widespread search for the specific reactions that it mediates. The first such reaction was discovered by Barker, Weissbach, and Smyth (5), when they examined the enzymatic isomerization of glutamic acid to /3-methylaspartic acid. They were... 

D-ervf/iro-V7-(tert-Butoxycarbonyl)-(l-methylaspartic Acid a-Methyl Ester (75) 2T ... 

The microcystins are a group of over 70 structurally related monocyclic heptapeptides containing seven peptide-linked aminoacids with the general structure of Cyclo-(D-alanine -X -D-MeAsp -Y" -Adda -D-glutamate - Mdha ), in which X and Y are variable L aminoacids, D-MeAsp is D-erytro- - methylaspartic acid and Mdha is N-methyldehydroalanine (Fig. 14.1). 

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. 

Microcystins are cyclic heptapeptides that share a general structure, as shown in Fig. 1 and Table 1, containing g-hnked D-glutamicacid (d-G1u), D-alanine Co-Ala), p-linked O-erythro-b-methylaspartic acid (o-MeAsp), A-methyldehydroalanine (Mdha), and a unique C20 p-amino acid, (25, 35, 85, 95)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4( ), 6( )-dienoic acid... 

Arginine or citrulline in concentration in excess of the optimal can inhibit both argininosuccinate synthetase or argininosuccinate lyase in tissue cultures (S6). Whether this is applicable to the conditions of synthesis of the urea in liver is uncertain. a-Methylaspartic acid also specifically inhibits argininosuccinate synthetase (B7, C4, SIO). 

C4. Cedrangolo, F., Della Pietra, G., Cittadini, D., Papa, S., and De Lorenzo, F., Urea synthesis in rats treated with a-D,L-methylaspartic acid. Nature (London) 196, 708-709 (1962). 

The enzyme methylaspartate ammonia lyase (P-methylaspartase, E.C. 4.3.1.2) is involved in the metabolism of branched pentanoic acids. The enzyme catalyzes the addition of ammonia to mesaconic acid (8) to yield i-tfireo-3-methylaspartate (9) as depicted in Scheme 12.6-3. The enzyme has been shown to be induced under anaerobic conditions in facultative anaerobes such as Citrobacter, Proteus, Escherichia coli and Enterobacter17, 81 and has been applied for the synthesis of 3-substituted (S)-aspartic acid derivatives, such as (2S,3S)-3-methylaspartic acid (9), (2S,3S)-3-ethylas-partic acid (11), and (2R,3S)-3-chloroaspartic acid (13) 7l In addition, a process for the preparation of dialkyl-(2S,3S)-3-ethylaspartates using methylaspartate ammonia lyase has been developed by Merck191. 

Fig. 7. Structure of one member of the amphomycin family where Dabe = D-erythro-a, /3-diaminobutyric acid Dab1 = l-threo-oc, /3-diaminobutvric acid Pip = D-pipecolic acid MeAsp = AT-methylaspartic acid. The amphomycin family member having (+)-3-anteisotridecenoic acid is shown not shown is...

Microcystins constitute a large family of cyclic heptapeptides with a high degree of homology in the amino acid sequence. As shown in Fig. 4, they are composed of D-Ala in position 1, two variable L-amino acids at positions 2 and 4, the 3-linked D-e/yt/iro-P-methylaspartic acid (MeAsp) in position 3, the novel C20 P-amino acid (25,35,85,95) - 3 - amino - 9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid... 

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-... 

H02CCH2CH2CH(NH2)C0jH (glutamic acid) Rearrangement of 16, 14.8.2.2 (table) CH3CH(C02H)CH(NH2)C02H (methylaspartic acid)... 

A second area of considerable. synthetic activity is the search for antagonists of iV-methylaspartic acid (NMDA). Receptors for glutamic and aspartic acids have been implicated in the pathology of severed neurological and neurodegenerative illnes.ses. 

The first chemical stractures of cyanobacterial cyclic peptide toxins were identified in the early 1980s and the number of fully characterized toxin variants has greatly increased since the 1990s. To-date there are 77 different microcystins isolated from cyanobacteria (Table 40.3). The first such compounds found in freshwater cyanobacteria were cyclic heptapeptides with the general stracture of cyclo-(D-alanine -X -D-MeAsp -Z" -Adda -D-Glutamate -Mdha ) in which X and Z are variable amino acids, o-MeAsp is D-eryt/jro-p-methylaspartic acid, and Mdha is A-methyldehydroalanine (Eigure 40.1a). The amino acid Adda, (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8- trimethyl-10-phenyldeca-4,6-dienoic acid, is the most unusual structural moiety in... 

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