Unsaturated Amino-acids

On the other hand, as synthetic equivalents of amino acids, unsaturated oxazolones are and will continue to be very important intermediates for the synthesis of new non-proteinogenic a-amino acids, particularly for the asymmetric synthesis of these compounds using diastereo- or enantioselective methodologies. In addition, the exocyclic double bond will continue as an important focus to build new constrained amino acids for the design of peptides with improved properties. 

Amino acid ammonia lyases [EC 4.3.1.n] Aminoacid - a, -unsaturated acid -1- NH3 Amino acid, unsaturated acid NH3 Potentiometric electrode, FET... 

Of the number of chromophoric derivatives of chiral amines for potential use in the establishment of their absolute configuration by BCD measurement only a few have proven to be generally useful. Of these, intensive investigation of the Af-salicylidene (Schiff base) derivatives of chiral primary amines, including unsubstituted and ring-substituted a- and S-arylalkylamines, a-amino acids, unsaturated and satnrated aliphatic and alicyclic amines, and amino sugars, has resulted in the formulation of the salicylidenamino chirality rule ° °. The application of this rule has recently been reviewed and has been successfully used for the establishment of absolute configuration of chiral primary amines in connection with other stereochemical studies. In related studies, the conformations of a series of pyridoxyl-L-a-amino acid Schiff bases were deduced from their CD spectra ... 

All higher animals and many microorganisms lack the biochemical ability to synthesize certain essential organic compounds. These essential nutrients include vitamins, certain amino acids, unsaturated carboxylic acids, purines, and pyrimidines. The aromatic amine p-aminobenzoic acid is an essential nutrient for those bacteria that are sensitive to sulfanilamide therapy. Enzymes within these bacteria use p-aminobenzoic acid to synthesize another essential compound called folic acid ... 

Azlactones have been of interest mainly as intermediates in the synthesis of other compounds. Saturated azlactones are obtained most often from the corresponding amino acids and are used in preparing derivatives of those amino acids. Unsaturated azlactones, on the other hand, usually are prepared by condensing an aldehyde with an acylglycine and are used in the synthesis of the corresponding amino and keto acids. Four methods by which azlactones can be prepared are discussed in the following paragraphs. 

Amino-aromatic carboxylic acids Unsaturated aromatic acid... 

The starting amino acid for nylon-11 is produced from methyl ricinoleate [141 -24-2] which is obtained from castor oil (qv). The methyl ricinoleate is pyrolized to methyl 10-undecylenate [25339-67-7] and heptanal [111-71-7]. The unsaturated ester is hydroly2ed and then converted to the amino acid by hydrobromination, followed by ammoniation and acidification. The CO-amino acid product is a soft paste containing water, which is dried in the first step of the polymeri2ation process. 

Also, Michael addition reactions occur between Ai-acylaminomalonic acid esters and unsaturated compounds, ie, acrolein [107-02-8] acrylonitrile [107-13-1y, acryhc acid esters, and amino acids result from hydrolysis of the addition products. 

Ring fission occurs readily in many of these compounds. For example, azlactones, i.e. 4JT-oxazolin-5-ones containing an exocyclic C=C bond at the 4-position (508), are hydrolyzed to a-benzamido-a,/3-unsaturated acids (509), further hydrolysis of which gives a-keto acids (510). Reduction and subsequent hydrolysis in situ of azlactones is used in the synthesis of a-amino acids e.g. 508 -> 507). 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

The configuration of the amine was retained, except in the case of amino acid derivatives, which racemized at the stage of the pyridinium salt product. Control experiments showed that, while the starting amino acid was configurationally stable under the reaction conditions, the pyridinium salt readily underwent deuterium exchange at the rz-position in D2O. In another early example, optically active amino alcohol 73 and amino acetate 74 provided chiral 1,4-dihydronicotinamide precursors 75 and 76, respectively, upon reaction with Zincke salt 8 (Scheme 8.4.24). The 1,4-dihydro forms of 75 and 76 were used in studies on the asymmetric reduction of rz,>S-unsaturated iminium salts. 

The A-phthalimidomalonic ester 8 can be further alkylated at the malonic carbon center with most alkyl halides, or with an o ,/3-unsaturated carbonyl compound thus offering a general route to a-amino acids 9. 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

The amino acid methionine is biosynthesized by a multistep roule that includes reaction of an inline of pyridoxal phosphate (PLP) to give an unsaturated imine. which then reacts with cysteine. What kinds of reactions are occurring in the two steps ... 

Diastereoselective preparation of a-alkyl-a-amino acids is also possible using chiral Schiff base nickel(II) complexes of a-amino acids as Michael donors. The synthetic route to glutamic acid derivatives consists of the addition of the nickel(II) complex of the imine derived from (.S )-,V-[2-(phenylcarbonyl)phenyl]-l-benzyl-2-pyrrolidinecarboxamide and glycine to various activated olefins, i.e., 2-propenal, 3-phenyl-2-propenal and a,(f-unsaturated esters93- A... 

An excellent method for the diastereoselective synthesis of substituted amino acids is based on optically active bislactim ethers of cyclodipeptides as Michael donors (Schollkopf method, see Section 1.5.2.4.2.2.4.). Thus, the lithium enolates of bislactim ethers, from amino acids add in a 1,4-fashion to various a,/i-unsaturated esters with high diastereofacial selectivity (syn/anti ratios > 99.3 0.7-99.5 0.5). For example, the enolate of the lactim ether derivative 6, prepared from (S)-valine and glycine, adds in a highly stereoselective manner to methyl ( )-3-phenyl-propenoate a cis/trans ratio of 99.6 0.4 and a syn/anti ratio of 91 9, with respect to the two new stereogenic centers, in the product 7 are found105, los. 

In a modified procedure, these additions lead to / ,y- and ) <5-unsaturated amino acid derivatives with cis/trans selectivity >99 1 and syn/anti diastereoselectivity >99 1 (see Section I.5.2.4.2.2.4.)108. 

Ail extremely useful method for the asymmetric synthesis of substituted amino acids, in particular glutamic acids, is based on optically active bislactim ethers of cyclodipeptides. The lithium etiolates of bislactim ethers (which are prepared easily from amino acids) undergo 1,4-addition to various a,/ -unsaturated esters to give -substituted 2,5-dihydropyrazine-propanoates203-205 with high diastereofacial selectivity, ratio (R/S) > 140-200 1. 

The reaction product with monoethanolamine acts as a thickening agent [41,101] and with alcohols as an emollient [40]. Also reaction products with amino acids and oligo- or polypeptides for use in cosmetic formulations are known [43]. Sorbitan esters from ether carboxylates are described as emulsifiers or mild surfactants in cosmetic formulations [39] and alkyl ether carboxylic acid taurides as nonirritant anionic surfactants for cosmetic cleaners in particular [44]. Using unsaturated ether carboxylates it is possible to make viscous formulations based on combinations of unsaturated and saturated ether carboxylates [111]. Highly purified alkyl ether carboxylates based on alcohol ethoxylates with low free alcohol content have also been described [112]. 

Alternatively, rigidification of the y-peptide backbone to avoid H-bonds between nearest neighbors can be achieved by the introduction of an a,y9-unsaturation into the backbone of each y-amino acid constituent (vinylogous peptides) ]208, 209]. Recent ab-initio calculations suggested that the a,/9-unsaturated y-peptide backbone might support the formation of helices with large 19- and 22-membered H-bonded pseudocycles ]221]. 

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