P-Methylaspartic acid

Freshwater cyanobacteria Microcystis, Oscillatoria, Ana-baena, and Nostoc produce several types of toxins, among which the most commonly detected are the hepatotoxic peptides microcystins. The general structure of the microcystins is cyclo-(D-Ala -X -D-MeAsp -Z -Adda -D-Glu -Mdha ), in which X and Z represent variable L-amino acids, D-MeAsp is D-eryf/iro-p-methylaspartic acid, Mdha is A-methyldehydroalanine, and Adda is the unusual C20 amino acid, (25,35,85,95)-3-amino-9-meth-oxy-2,6,8-trimethyl-10-phenyldeca-4( ),6( )-dienoic acid (Fig. 1). The structural differences in the microcystins mainly depend on the variability of the two L-amino acids (denoted X and Z), and secondarily on the methylation or demethylation of D-MeAsp and/or Mdha. More than 60 microcystins have been isolated from bloom samples and isolated strains of cyanobacteria. 

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... 

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... 

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. 

Amino-acid analogs and uncommon L-amino acids W-acetyl-aspartate, W-acetyl-serine, oi-amino-n-butyrate, 3-aminoisobutyrate, aspartate ethyl or methyl ester, citrulline, cysteate, fumarate, glutathione, homoserine, erythro- and threo-p-hydroxyaspartate, isoasparagine, isoserine, malate, a- and p-methylaspartate, methylserine, phenol, serine amide, serine methyl ester, succinate [498, 747]... 

The isomeric ratio obtained in the previous reaction is the result of an equilibrium process because diastereomerically pure threo ( )-N-phtha-loyl-3-methylaspartic anhydride yields a similar mixture, together with elimination products (Scheme 25). Several P-hydride and/or COj elimination-insertion processes account for isomerization at C-3 and also at C-2. As a result, when enantiomerically pure anhydride 65 is used, a racemic mixture of 3-methylaspartic acid derivatives is obtained. 

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 (d-Ala), p-linked D-erythro-b-methylaspartic acid (d-MeAsp), iV-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 (Adda). The other two t. -amino acids are variable (denoted X and Z) and are found in positions 2 and 4 of the cyclic structure. The single-letter abbreviation of the variable amino acids is used to distinguish different microcystins for example, the most commonly occurring microcystin... 

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

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