Dehydroalanines

Use of Qi-acetamidoacrylate esters in the Heck reaction allows for the introduction of a dehydroalanine side-chain. The dehydrotryptophans can be reduced catalytically, and this reduction can be done enantioselectively[17]. 

Fig. 9. Stmcture of nisin where Dha = dehydroalanine Dhb = dehydrobutyrine Abu = a-aminobutyric acid Ala-S-Ala = me50-lanthionine and Abu-S-Ala = t/ireo-methyllanthionine. The first amino acid residue (Ala or Abu) of the lanthionine or methyUanthionine is a D residue all other amino...

The related 5-diphenylphosphinothioyl group (Ppt group) has also been cleaved using these conditions. The Mpt derivative of cysteine is not stable to DBU it forms dehydroalanine. The Mpt group is stable to TFA and to I M HCI, but not to HBr/AcOH or 6 M HCI. ... 

The Michael addidon of nitto compounds is a useful method for the preparadon of various naniral products The Michael kldidon of nittoalkanes to dehydroalanines gives ynitto-ct-amino acids, which provides a convenient synthesis of side-chain modified ct-amino acids fEq 4 114 " Transformadons of Y-nitto-ct-amino acid derivadves into ct-amino adds occur by... 

Silica gel [11] or alumina [11a, 12] alone, or silica and alumina together modified by Lewis-acid treatment [13] and zeolites [14], have been widely used as catalysts in Diels-Alder reactions, and these solids have also been tested as catalysts in asymmetric Diels-Alder reactions [12,13b,14]. Activated silica gel and alumina at 140 °C were used [15] to catalyze the asymmetric cycloaddition of (-)-menthyl-N-acetyl-a, S-dehydroalaninate (3) (R = NHCOMe) with cyclopentadiene in the key step for synthesizing optically active cycloaliphatic a-amino acids. When the reactions were carried out in the absence of solvent, a higher conversion was obtained. Some results are reported in Table 4.5 and compared with those obtained by using silica and alumina modified by treatment with Lewis acids. Silica gel gives a reasonable percentage of conversion after 24 h with complete diastereofacial selectivity in exo addition. 

Table 4.5 Solvent-free Diels-Alder reactions of (-)-menthyl N-acetyl-a,/l-dehydroalaninate (3, R = NHCOMe) with cyclopentadiene (1) at 25 °C...

A completely distinct enzyme has been found in a number of organisms, which carry out the metabolism of amino acids. In this group, a pyruvoyl group is covalently bound to the active enzyme that is produced from a proenzyme in a self-maturation process (Toms et al. 2004). The proenzyme contains a serine residue that undergoes rearrangement to an ester followed by conversion into the (3-chain of the enzyme and a dehydroalanine residne that forms the A-terminal pyruvoyl group of the a-chain. This type of enzyme has been fonnd for a number of important decarboxylations ... 

Modified amino acids such as N-acyl-dehydroalanine polymers and copolymers with N-vinyl-N-methyl acetamide seem to be particularly effective [396]. The crystallization kinetics in the presence of polyvinylpyrrolidone and tyrosine have been tested by time-resolved experiments [981]. An influence is evident on the particle size distribution of the hydrate [1433]. 

Takemoto et al. applied the Pd-catalyzed coupling reaction to N-phlhaloyl dehydroalanine 102 and benzaldehyde (Scheme 27) [41]. Instead of hydrosilanes, M-BuiiSnH was capable of serving as a hydrogen donor to promote C - C bond formation giving 103. 

TV-Benzylidene dehydroalanine, however, could not be isolated by this method because the compound decomposed during work up at room temperature.[ 181 CDI was inert toward a series of dipeptides containing a serine residue in the TV-terminal position... 

Formation of the very unstable dehydroalanine derivatives A p-dimethylaminophe-nyl- and Af-p-nitrophenyhnethylenedehydroalanine methyl ester could only be verified by -NMR. Because of Michael-type reactions with cuprates, the iV-arylmethylenedehy-droalanine methyl esters have been applied as building blocks in the synthesis of amino acids.[18]... 

Very recently, Reetz, Ma and Goddard reported phosphoramidites based on BINOL bearing a single ortho-substituent (Scheme 28.10) [69]. These ligands are also chiral on phosphorus, such that the synthesis results mostly in diastereo-mers which have to be separated. In several cases, however, one of the diaster-eomers was formed exclusively. Some of the ligands afford high ee-values in the hydrogenation of methyl N-acyl dehydroalanine and dimethyl itaconate. 

The reaction of //-protected dehydroalanine methyl esters (e.g. 56, 59) with other indoles 58 can also be effected to give the corresponding dehydrotryptophans 60, invariably as the Z-isomers [81]. Murakami, Yokoyama and co-workers also studied oxidative couplings of acrylates, acrylonitrile, and enones with 2-carboethoxyindole, 1-benzylindole, and l-benzyl-2-carboethoxyindole and PdCfe and CuCk or Cu(OAc) 2 to give C-3 substitution in 50-84% yields [82, 83]. 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

Carlstrom and Frejd described the one-step conversion of o-diiodobenzene (or iodobenzene) with N-Boc dehydroalanine methyl ester to give vV-Boc-2-carbobenzyloxyindole in 30% yield [384],... 

It has been demonstrated recently that the dichromate oxidation of wool cystine proceeds as shown in Scheme 5.18. The cystine crosslinks (5.73) are cleaved to give dehydroalanine (5.74) and perthiocysteine (5.75) residues, the latter being readily oxidised by the dichromate ions to yield cysteine-S-sulphonate (Bunte salt) residues (5.76). 

Scheme 8 a-Amino acids from dehydroalanines via enantioselective H-atom transfer... 

FIGURE 3.10 Deprotection of functional groups by beta-elimination.17 (A) Removal of a labile proton beta to a good leaving group leads to release of the protector as the didehydro compound. (B) Recently developed protectors (Samukov et al., 1988) also designated untra-ditionally as 4-nitrophenyl- (C) Transformation of an O-protected serine residue into a dehydroalanine residue by hefa-elimination. 

Die Methode ist an dem Protein Ribonuklease ausprobiert worden Sokolovsky nnd Patchornik (P5)). Es hat sich hicrbci als notwendig erwiesen, nach der Einfiilirung des Dinitrophenyl-Restes eine Acetylie-ning der Aminogruppcn dcs Proteins vorzunehmen, um Reaktionen des Dehydroalanins mit Aminogruppcn zu vermeiden. 

A number of nonprotein amino acids with unsaturated side chains have been isolated. Many of these contain alkene side chains, but some alkyne side chains containing amino acids have also been identified. Nonprotein dehydroamino acids do not have an a-stereocenter these amino acids are still classified under this category. Dehydroamino acids are generally biosynthesized by the enzymatic elimination of a leaving group at the /3-carbon. For example, serine and threonine are enzymatically dehydrated to give dehydroalanine and dehydrobutyrine, respectively. A similar biosynthetic pathway is hypothesized for dehydroamino acids found in nonribosomal peptides, such as nodularins and microcystins. ... 

The first reaction is p-elimination in cysteine, serine, phosphoserine, and threonine residues due to attack by hydroxide ion, leading to the formation of very reactive dehydroalanine (DHA). In a cystine residue, this results in rupturing of the disulfide bond and liberation of a sulfide ion and free sulfur (Figure 13.4). Nucleophilic additions of the s-amino group of the protein-bound lysine to the double bond of DHA residue causes crosslinking of the polypeptide chain. After hydrolysis, a mixture of L-lysino-L-alanine and L-lysino-D-alanine, with probably a small proportion of dl and dd isomers,... 

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