P-Amino-alanine

Table 7. Fungicidal Activity of Amidotransferase Inhibitors Derived from P-Amino-alanine.

Fig. 9 shows some examples, the list of which might be expanded almost arbitrarily. The only limitation hes in the reactivity of the aryl cuprates, which means that pyridyl or thienyl residues cannot be introduced yet. On the other hand the flexibility of the bisepoxide method is demonstrated by the synthesis of 2,3-diamino-propionic acid (p-amino-alanine) which is a constituent of antibiotic cyclo-peptides like tuberactinomycin A or, in form of the N-methyl derivative L-BMAA, occurs in the seeds of the local sago palm and had notoriously caused the Guam disease [8], with a certain kind of Alzheimer and Parkinson symptoms, until the American conquest of the island in World War II led to a change in nutrition (Fig. 10). 

Aminopropanoic acid known as 3 alanine It IS a p amino acid that makes up one of the stmctural units of coenzyme A... 

The relevance of the palladium-catalyzed amidocarbonylation for natural product synthesis has been demonstrated with the multi gram-scale preparation of the central amino acid of chloropeptin I ((S)-3,5-dichloro-4-hydroxyphenylglycine) as well as methionine and p-chlorophenyl alanine via the combination of amidocarbonylation and enzymatic hydrolysis (Table 4) [44]. 

These bases are then degraded to two P-amino acids, uracil to P-alanine and thymine to P-aminoisobutyrate. 

In the heterocyclic series, racemic 3-(fur-2-yl)alanine has been prepared from furfural using this approach. In addition, (3-(pyrid-3-yl)alanine, ° p-(quinol-3-yl)alanine, ° a p-(benzofuranyl)alanine derivative, 2-amino-3-(2,2 -bipyridi-nyl)propanoic acid, and some interesting derivatives of histidines—in particular 1-alkylhistidines with amphiphilic properties have all been synthesized using this methodology. The complete reaction sequence starting from an aldehyde and an A-acylamino acid derivative is shown in Scheme 7.150. 

The Silurian Wills Creek, Tonoloway and Keyser Formations were tested for residual amino acids (Table V). The following were found cystine( ), histidine(P), arginine, glycine(P), aspartic acid(P), glutamic acid(P), threonine, alanine, valine, leucine. 

The aza-Michael reaction yields, complementary to the Mannich reaction, P-amino carbonyl compounds. If acrylates are applied as Michael acceptors, P-alanine derivatives such as 64 and 65 are obtained. The aza-Michael reaction can be catalyzed by Bronsted acids or different metal ions. Good results are also obtained with FeCl3, as shown in Scheme 8.29. The addition of HNEt2 to ethyl acrylate (41f), for example, requires 10mol% of the catalyst and a reaction time of almost 2 days [94], The addition of piperidine to a-amino acrylate 41g is much faster and yields a,P-diaminocarboxylic acid derivative 65 [95]. 

P-Elimination and then replacement reaction of an a-amino acid with a nucleophile is very attractive from the viewpoint of synthetic organic chemistry because various P-substituted alanines may be prepared from a simple a-amino acid, such as serine, and nucleophiles. A reaction catalyzed by tryptophan synthase - the formation of tryptophan from serine and indole - is one of the most well-known P-elimination and replacement reactions (Scheme 2.7). Here, an aldimine Schiff base is derived from reaction of the enzyme-bound PLP with serine, which then dehydrates to give the Schiff base of PLP with 2-aminoacrylate. Indole then adds to the vinyl Schiff base, generating tryptophan after lysine aminolysis of the Schiff base product. 

The nonenzymatic 1,2-migration of an amino group in Scheme 1 is an efficient way to transform 2-methyl-3-bromoalanine ethyl ester into 2-methyl- alanine ethyl ester. It is possible that this nonenzymatic counterpart to the enzymatic rearrangement may serve as the foundation for an efficient synthetic transformation of a-amino acid derivatives into P-amino acid derivatives, which may in turn be of some use in the drug industry. Under conditions of low concentrations of tributyltin hydride in the process of Scheme 1, the ratio of P-amino acid ester to a-amino acid ester is 13/1, presumably because the radical 5 is more stable than 4 owing to the delocalization of the unpaired electron into the adjoining carboethoxy group. 

One of the invariant amino acids is a unique P-amino acid called Adda (2S,3S,8S,9S)-3 amino-9 methoxy-2,6,8-trimethyl-10-phei5fldeca-4,6-dienoic acid is the most unusual structure in this group of cyanobacterial cyclic peptide toxins). A two-letter suffix (XY) is ascribed to each individual toxin to denote the two variant amino acids (Carmichael 1988). X is commonly leucine, arginine, or tyrosine. Y is arginine, alanine, or methionine. Variants of all the invarianf amino acids have now been reported, e.g., desmethyl amino acids and/or replacement of the 9-methoxy group of Adda by an acetyl moiety. Currently there are in excess of 60 variants of microcystin that have been characterized (Rinehart 1994 Sivonen and Jones 1999). Of these 60 compounds, microcystin-LR would appear to be the microcystin most commonly found in cyanobacteria. It is also common for more than one microcystin to be found in a particular strain of cyanobacterium (Namikoshi 1992 Lawton 1995). The microcystin variants may also differ in toxicity (Carmichael 1993). The literature indicates that hepatotoxic blooms ofM aeruginosa containing microcystins occur commonly worldwide. 

Glowiak, T., Dao, C.N., Legendziewicz, J., and Huskowska, E. (1991) Structures of neodymium(III) complexes with amino acids (1) catena-poly[[triaquatrichloroneodymium(lll)]-p-(f -alanine-0,0 ) (II) pentaaquachloro-p-(L-proline-0,0 )-neodymium(III) hexaaqua-p-(L-proUne-0,0 )-neodymium(III) pen-tachloride. Acta Crystallographica Section C, 47 (1), 78-81. 

Amino Acids. Pseudoephedrine has been used as a chiral auxiliary for the preparation of both a-substituted and a,p-disubstituted p-amino acids. Alkylation of p-alanine was shown to furnish an efficient, inexpensive, and enantioselective route to a-alkyl p-amino acids (eq 23). ... 

In the special case of (3-Iactones, where small-angle strain is an important factor, alkyl-oxygen cleavage is observed (Bal2 mechanism, as in the similar case of hydrolysis of (3-lactones, 16-59), and the product is not an amide but a p-amino acid (p-alanine). 

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... 

Notice that the isoelectric points of the 13 amino acids without an acidic or basic side chain are simply the average of the two dissociation constants, pifai and pifa2. Alanine, for instance, has pJEgi = 2.34 and 9-69, so the p/ of alanine is (2.34 + 9.69)/2, or 6.01. For the four amino acids with either a strongly or weakly acidic side chain, the pi is the average of the two lowest pi a values, and for the three amino acids with a basic side chain, the pZ is the average of the two highest pK values. 

Several studies of the biosynthesis of chloramphenicol have led to the conclusion that it is formed via the shikimic acid pathway, specifically from chorismic acid. An arylamine synthetase promotes formation of p-amino-L-phenyl alanine (1 ) 50>51. This product is converted to chloramphenicol (15) by oxidation of the amine function to a nitro group, by hy-droxylation of the benzylic methylene group, reduction of the carboxyl... 

The DNA sequence M, shown below, is the sense strand from a coding region known to be a mutational hot spot for a gene. It encodes amino acids 21 to 25. Given the genetic and amino acid codes CCC = proline (P), GCC = alanine (A), TTC = phenylalanine (F), and TAG = stop codon, which of the following sequences is a frame-shift mutation that causes termination of the encoded protein ... 

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