Dehydro p-amino acids

X,P-Dehydro-a-amino acids are prepared by elimination of HN02 from P-nitro-a-amino acids, which are prepared by reaction of a-bromoglycine derivatives with alkyl nitronates (see Eq. 7.135).181 This process is a new type of the Michael addition of nitro compounds followed by elimination of HNOz. Such unusual amino acids are interesting as enzyme inhibitors.182... 

Transamination reactions have also been described for 4-(aminomethylene)-2-substituted-5(47T)-oxazolones. As an example, displacement of the A-methyl-heteroarylamino group of a 4-[(A-heteroaryl-A-methyl)aminomethylene]-2-phen-yl-5(47T)-oxazolone 420 by an a-amino acid derivative produces p-amino-a,(3-dehydro-a-amino acid precursors 421 (Scheme 7.137). ... 

The first family is represented by peptides based on a, 3-dehydro a-amino adds in which a C=C bond confers rigidity and electronic Y-conjugation on the system (Section 11.1). Peptides rich in these amino acids are widespread in nature, particularly as antibiotics, and possess interesting conformational properties. 1-11 In addition to the E and Z configurational isomers, occurring when two different atoms (substituents) on CP are present, fully-extended, characteristically flat conformations or p-tums and 310/a-helices may be induced by u,p-dehydro a-amino acids. 

A large number of a, 3-didehydro-a-amino acids have been identified as constituents of relatively low molecular weight cyclic compounds from microbial sources. However, the presence of a,p-didehydroalanine in bacterial as well as in mammalian histidine ammonia lyase and in phenylalanine ammonia lyase shows that the occurrence of a,p-didehydro-a-amino acids is not limited to small molecules alone 8 These residues are incorporated in natural sequences by posttranslation modification. a,p-Didehydro-a-amino acids have also been postulated to be precursors in the biosynthesis of several heterocyclic metabolites including penicillin and cephalosporin 9 Other well-known compounds containing ,( -di-dehydro-a-amino acids are nisin 10,11 (a food preservative112 ), subtilin (a broad spectrum antibiotic) 13 and some of the metabolites isolated from Streptomyces strains such as gri-seoviridin 14 ... 

The formation of stereogenic C-N bonds by hydrogenation of the enamine structure is not only limited to amino acids. Likewise, chiral 1,2-aminoalcohols or 1,2-diamines can be produced by the enantioselective hydrogenation of dehydro-p-amino alcohols (or their esters) and of dehydro-a-amino aldoximes, respectively (eq 6 and eq 7, Thble 2). Esters and aldoximes thus obtained can be converted into the corresponding alcohols or diamines by standard methods. By this means, simple amines with one aryl group attached to the double bond can also be hydrogenated with high enantioselectivity. ... 

Ranu et al. have developed a mild and efficient method for the synthesis of a-dehydro-p-amino esters and nitriles by nucleophilic addition of amines to MBH acetates in water at room temperature without using any basic, acidic or metal catalyst. The reactions yielded only y-addition products, providing, with high stereoselectively, ( )-isomers in the case of MBH adducts bearing a carboxylic ester moiety and (Z)-isomers for adducts containing CN functionality (Scheme 3.123). An interesting stereoselective transformation of MBH adducts into cinna-mylamines via treatment with DMF-DMA has been described by Kim and coworkers (Scheme 3.124). ... 

Kolasa, T. An Effective Synthesis of a,P-Dehydro-a-amino Acid Derivatives from N-Acyl-N-hydroxy-a-amino Acid. Synthesis 1983, 539. 

The red pigment, obtained from the interaction of amino acids and dehydro-ascorbic acid and shown to have structure 31 (p. 54) by Kurata et al.,194 provides another model chromophore for Maillard reaction products. 

For example, P. Mathur, S. Ramakumar and V. S. Chauhan. Peptide design using alpha, beta-dehydro amino acids from beta-turns to helical hairpins. Biopolymers, 76 (2004), 150-61. 

However, while the Indane analog shows considerably less activity in the guinea pig ileum and mouse vas deferens assays chan [Leu ]enkephalln, the tetralin analog is more active in the guinea pig ileum (p-receptor) assay and much less active in the mouse vas deferens (6-receptor) assay than [leu ]enkephalin. Implying an Increase of receptor specificity by this conformational restriction. The use of dehydro amino acids to Induce rigidity and increase hydrophoblclty of the enkephalins has resulted in the u-selective [AAla , Leu ]enkephalln and the 6-selective [D -Ala ,... 

Lantibiotics are small, membrane-active peptides (< 5 kDa) containing the unusual amino acids lanthionine, P-methyl-lanthionine, and the dehydrated residues dehydro alanine and dehydrobutyrine e.g. nisin, lacticin 481, carnocin U-149, lactocin S, sublancin 168 [29-38]. The intrachain positioning of these polycyclic structures of the lantibiotics has been used to group them into linear (Group lA) or circular (Group IB) lantibiotics [39]. Based on similarities in the... 

Asymmetric Hydrogenation of p,p-Disubstituted a-Dehydro-amino Acid Derivatives... 

Essentially the same results were later obtained with various prochi-ral substrates a-dehydro amino acids, enamides, - P-dehydroamino acid, unsaturated phosphonate, ° and itaconic ester. All studied substrates reacted instantaneously with 28a, b at -100°C yielding high ee s of the hydrogenation products—either equal or comparable to the ee s observed in the corresponding catalytic reactions. - ... 

This peptide is formed by several strains of Streptococcus lactis (Langfield-N-group). It contains a number of unusual amino acids, namely dehydroalanine, dehydro-P-methy 1-alanine,... 

Hydrogenation reactions are benchmarked to standard substances such as simple alkenes (e.g., 1-hexene), and asymmetric hydrogenations to a,P-unsaturated functionalized olefins (e.g., dimethyl itaconate) and a-dehydro amino acid esters. Thus, numerous ligands have been tested with a great diversity of structural and electronic properties. 

Aziridine-2-carboxylic acid residues in peptides are isomerized with Nal and acetone to the corresponding dehydro-amino-acid component. p-Hydroxy-amino-acids are effectively dehydrated by NiV -carbonyldi-imidazole to give the corresponding dehydro-amino-acids. 2-Azidocarboxylic esters (286) are effectively converted into A-acetyldehydro-a-amino-acid esters (287) (Scheme 141) 4oa Esters of A-acyl-2-(diethoxyphosphoryl)glycine have been used in the synthesis of dehydro-amino-acid esters. ... 

In summary, L-cysteine is the specific precursor of the P-lactam moiety of benzylpenicillin. The amino acid is incorporated with retention of configuration at the P-carbon and a 2,3-dehydro intermediate is not involved. 

Ahp 3-amino-6-hydroxy-2-piperidone Abu a,p-dehydro-2-aminobutanoic acid, supposed Z Figure 23.13 Examples of dolastatins isolated by the team of Professor C.R. Pettit. 

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