A-Acylated amino acid derivatives

In the case of A-acylated amino acid derivatives, the oxidation has to take place via an indirect electrochemical process using chloride ions as redox catalysts. In methanol as solvent, methylhypochlorite is formed as oxidant, which yields, via -chlorination, HC1 elimination, and methanol addition, the a-methoxylated amino acids as amidoalkylation reagents [27] ... 

Aminoacylases catalyze the hydrolysis of A-acyl amino acid derivatives, with the acyl groups preferably being acetyl, chloroacetyl, or propionyl. Alternatively, the corresponding A-carbamoyl- and A-formyl derivatives can be used [132], Enzymes of the amino acylase type have been isolated from hog kidney, and from Aspergillus or Penicillium spp. [133-135]. The versatility of this type of enzyme has been demonstrated by the resolution of racemic iV-acetyl tryptophan, -phenylalanine, and -methionine on an industrial scale using colunm reactors (Scheme 2.15) [136, 137]. 

Before synthetic chiral stationary phases were developed, attempts were made to use naturally occurring chiral materials for the stationary phase. Quartz, wool, lactose and starch were inadequate but triacetylated cellulose has met with some success. The synthetic stationary phases introduced by Pirkle are able to interact with solute enantiomers in three ways, one of which is stereochemically dependent. Typically these interactions are based on hydrogen bonding, charge transfer (rc-donoi -acceptor based) and steric repulsive types. An independent chiral stationary phase therefore consists of chiral molecules each with three sites of interaction bound to a silica (or other) support. Early work in this area demonstrated that 5-arginine bound to Sephadex would resolve 3,4-dihydroxy-phenylalanine, and that direct resolution of chiral helicenes could be accomplished with columns packed with 2-(2,4,5,7-tetranitro-9-fluorenylideneaminoxy)-propionamide or tri-P-naphthol-diphosphate amide. Amino acid esters have also been resolved with a silica bound chiral binaphthyl crown ether, but better separations are achieved with A-acylated amino acid derivatives with amino-acid derived chiral stationary phases. 

The intramolecular cycloaddition of munchnone intermediates (derived from the cyclodehydration of A-acyl amino acids) with 1,3-dipolarophiles was employed to construct the mitomycin skeleton. Thus, heating alkynyl acids 23 with acetic anhydride forms the intermediates 24 which undergo cyclization with loss of carbon dioxide to afford the 4-oxo-tetrahydroindoles 25 <96TL2887>... 

The advantage of trimethylsilyl (TMS) derivatives lies in the simplicity of the derivatization procedure, which is carried out by the addition of N,0-bis(trimethylsilyl)trifluoroacetamide (BSTFA) in acetonitrile and heating for approximately 2 h at 150 °C under anhydrous conditions in a sealed tube. However, there may be problems owing to the formation of multiple derivatives of each amino acid. Another technique involves the formation of n-butyl esters of the amino acids and their subsequent trimethylsilylation by a similar procedure. The n-butyl esters are formed by heating the amino acids for 15 min in n-butanol and HC1 and these are then converted to the A-TMS-n-butyl ester derivatives. A-acyl amino acid alkyl esters are commonly used. Acetylation of the butyl, methyl or propyl esters of amino acids,... 

Fig. 8.26. The two-step activation of oxazolidin-5-one derivatives of peptides and N-acy/ amino acids (8.190). Hydrolysis (Reaction a) yields an A-(l-hydroxyalkyl) derivative that breaks down to liberate the peptide or A-acyl amino acid (Reaction b) [247] [248],...

The chiral distinction capability of cinchonan carbamate CSPs for underivatized amino acids has not been fully elucidated yet, in contrast to the large embodiment of A-acylated and A-arylated amino acid derivatives vide infra). However, it seems that chiral amino acids can be successfully resolved into enantiomers if the amino acid side chain R residue) contains a functionality that represents a strongly interactive binding site with the selector such as an extended aromatic ring system like in thyroxin (T4). 

Derivatives of the steroids androstene and pregnene have been transformed directly into A-acyl amino acids by an orthogonal catalysis procedure, utilizing [RhCl(nbd)]2 and Co2(CO)8 (Scheme 11). The rhodium phosphine catalyst (generated in situ in the presence of syn-gas and phosphine) affects hydroformylation of the internal olefin to generate aldehyde. In the presence of Co2(CO)8, A-acyl amino acids are obtained as the major products. An unstable amido alcohol intermediate, formed by reaction of the amide with aldehyde, is proposed to undergo cobalt-catalyzed GO insertion to yield the desired A-acyl amino acid. 

Activated A-alkoxycarbonyl amino acid derivatives, on the other hand, do not cyclize as readily as A -acyl amino acids, and therefore racemize more slowly. Accordingly, solid-phase peptide synthesis is generally performed by acylation of support-bound amines with activated A -alkoxycarbonyl amino acids. Examples of the preparation of peptides by the inverse strategy (first amino acid linked to the support via its amino group as carbamate activation of support-bound AAacylamino acids) have, nevertheless, been reported [13-16]. 

A series of acyl derivatives of the amines at various positions have been prepared, including benzoyl derivatives,carbonates, and acyl derivatives with A-acylated amino acid and with o>-chlorocarboxylic acid residues. The latter have been reduced with LiAlH4 to the corresponding alkylamino derivatives. ... 

Similarly, the exceptional acid stability of the A -Fmoc amino acid derivatives permits the preparation of the related acid chloridesP and fluorides, which are also powerful acylating intermediates for peptide synthesis (see Section 3.3). 

In combinatorial chemistry, the development of multicomponent reactions leading to product formation is an attractive strategy because relatively complex molecules can be assembled with fewer steps and in shorter periods. For example, the Ugi multicomponent reaction involving the combination of an isocyanide, an aldehyde, an amine, and a carboxylic acid results in the synthesis of a-acyl amino amide derivatives [32]. The scope of this reaction has been explored in solid-phase synthesis and it allows the generation of a large number of compounds with relative ease. This reaction has been employed in the synthesis of a library of C-glycoside conjugated amino amides [33]. Scheme 14.14 shows that, on reaction with carboxylic acids 38, isocyanides 39, and Rink amide resin derivatized with different amino acids 40, the C-fucose aldehyde 37 results in the library synthesis of C-linked fucosyl amino acids 41 as potential mimics of sialyl Lewis. ... 

The first protease-catalyzed reaction in ILs was the Z-aspartame synthesis (Scheme 10.7) from carbobenzoxy-L-aspartate and L-phenylalanine methyl ester catalyzed by thermolysin in [BMIM] [PF ] [ 14]. Subtilisin is a serine protease responsible for the conversion of A -acyl amino acid ester to the corresponding amino acid derivatives. Zhao et al. [90] have used subtilisin in water with 15% [EtPy][CF3COO] as cosolvent to hydrolytically convert a series of A -acyl amino acid esters often with higher enantioselectivity than with organic cosolvent like acetonitrile (Scheme 10.8, Table 10.2). They specifically achieved l-serine and L-4-chlorophenylalanine with an enantiomeric access (ee) of-90% and -35% product yield which was not possible with acetonitrile as a cosolvent [90]. Another example is hydrolysis of A-unprotected amino acid ester in the presence of a cysteine protease known as papain. Liu et al. 

The properties of the N-acyl amino acid derivative and the amino acid itself can be important if crystallization is employed to ensure high optical purity. However, in the experience of the authors, it is seldom a problem. Only 3-pyridylalanine could not be purified to high optical purity by recrystallization. Use of enzymes to enhance enantiomeric excess as well as allowing the use of mild hydrolysis conditions has been advocated by others [12]. Amino acids are surprisingly stable to acid-induced racemization. 

In order to clarify whether the influence of the A-substituent group in an amino acid surfactant on micellization is present in a mixture of A-acyl amino acid surfactants, Miyagishi et al. [120] determined the cmc values of mixtures of sodium salts of A-lauroyl amino acid derived from glycine, valine, and phenylalanine. The results indicate that the steric hindrance of A-substituent is not always significant in the formation of mixed micelle. The interaction between the surfactants with and without a substituent group was very small. The interaction parameter was zero for lauroyl phenylalanine/SDS. A strong interaction was observed in a mixture of C12EO6 and A-lauroyl valinate. 

Ammonia is sufficiently nucleophilic that addition to the double bond of a conjugated ester is possible, even in the presence of the acyl carbon. Similarly, amines undergo conjugate addition. In both cases, the product is a 3-aminopropan-oic acid derivative (a P-amino acid derivative). Both ammonia and amine nucleophiles will be discussed in this section. 

Based on Mannich-type reactions of N-acryliminoacetates with silyl enol ethers, a new method for the preparation of N-acylated amino acid derivatives via nucleophilic addition to N-acrylimino ester has been developed using a polymer-supported amine and scandium catalysts (Scheme 12.5) [9]. Ethyl N-benzoyl-2-bromoglycine was used as a substrate. It could be readily converted to reactive N-acrylimino ester in situ by treatment with a base. Immobilizations of the amine and the scandium species into polymeric supports prevented loss of activity of the catalyst. The method is simple and provides a convenient method for the preparation of N-acrylated amino acid derivatives. 

The efficiencies of inhibitors (t]) on mild steel and stainless steel summarized in Table 9-6 show that three of the acyl amino acids (derivatives of aspartic and glutamic acid) are much more effective corrosion inhibitors on mild steel than on stainless steel. This points to the importance of the carboxyl group in inhibitor molecules and the significance of simple A -substitution. 

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