A-amino acid glycine

Sketch the tetrapeptide obtained from four molecules of the a-amino acid glycine. 

One advantage of this method is the predictable stereochemistry of the alkylation reaction, since the electrophile adds exclusively irons to the substituent in the 2-position. Because of the large variety of usable electrophiles, the bis-lactimether method provides a powerful and versatile tool for preparing a large array of a-amino acids ( glycine derivatives) and a,a-di-substituted amino acids in optically active form. 

Optically pure or almost pure a-amino acids (glycine derivatives) can be obtained by reacting 3,6-dialkoxy-2,5-dihydropyrazines 1 (prepared from glycine and an appropriate optically pure amino acid as chiral auxiliary) with alkylating agents, followed by hydrolysis (see Table 1). 

Perhaps the most spectacular success of explanations based on solvation of ground states, published to date, is the dissection of activation parameters for solvolysis of t-butyl chloride in mixtures of ethanol and water, first discussed by Winstein and Fainberg (1957). The complex variation of AH and AS (Fig. 21) has been shown to be due almost entirely to ground state solvation effects, at least for the solvents ethanol—40% ethanol/water studied by Arnett et al. (1965). For 90%, 80%, 70%, 60%, 50% and 40% ethanol/water the parameter AH1 for solvation of the transition state (by transfer from the gas phase) was calculated to be linearly proportional to the corresponding value of AS, as expected from the behaviour of simple salts. The point for pure ethanol did not fall on the calculated line, and this was attributed to nucleophilic solvent assistance. The variation in AG, AH and AS (Fig. 21) can be reproduced remarkably well using ethane and the zwitterionic a-amino acid, glycine, as model compounds (Abraham et al., 1975 see also Abraham, 1974 Abraham and Abraham, 1974). 

Other workers (309) have extended this reaction and found that mixtures of a-amino acids (glycine, alanine, phenylalanine, tyrosine, tryptophan, leucine, methionine, cysteine) and benzil when heated to 180-220° gave good yields of 2,3,5,6-tetraphenylpyrazine, and a mechanism also involving an a-amino ketone was proposed. Benzoin with glycine, alanine, phenylalanine, or tyrosine at elevated temperatures similarly gave tetraphenylpyrazine. 

To keep names of amino acids and peptides to manageable proportions, there are agreed conventions for nomenclature (see the footnotes to Table 1.1). The simplest a-amino acid, glycine, would be depicted H—Gly—OH in the standard three-letter system, the H— and —OH representing the H20 that is expelled when this amino acid undergoes condensation to form a peptide (Figure 1.2). The three-letter abbreviations therefore represent the amino-acid residues that make up peptides and proteins. 

Various L-a-amino acids (glycine, L-alanine, L-valine, L-aspartic acid, L-isoleucine, histidine) have been converted into the corresponding N-carboxyanhydrides by N-protection with benzyl chloroformate and further reaction with SOCI2 [846-853]. 

Except for the simplest a-amino acid, glycine, NH2CH2COOH, the a-amino acids exist as enantiomers, or optical isomers. Such isomers are mirror images. Any molecule having one tetrahedral carbon atom bonded to four different groups of atoms exhibits optical isomerism. The mirror-image isomers are referred to as the D-isomer and the L-isomer their three-dimensional structures are represented by the following formulas ... 

Note that the amino-acids, because of their salt-like nature, usually decompose on heating, and therefore seldom have sharp melting-points. Furthermore, all naturally occurring amino-acids are a-amino-acids, and consequently, with the exception of glycine, can exist in optically active forms. 

All the amino-acids of physiological importance are a-amino-acids, e.g. (in addition to the above compounds), alanine or a-amino-propionk acid, CHaCH(NH,)COOH, and leucine or a-amino-Y-dimethyl-rt-butyric acid, (CH,)aCHCH,CH(NHa)COOH, and naturally occurring samples (except glycine) are therefore optically active. 

The influence of a large number of oc-amino acids on the values of and k at have been determined. These a-amino acids included glycine, L-valine, L-leucine, L-phenylalanine, L-tyrosine, L-tryptophan, NOrmethyl-L-tryptophan (L-abrine), N-methyl-L-tyrosine, N,N-dimethyl-L-tyrosine and p -me thoxy-N-me thyl -L -phenyl al anine. 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from o -amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the o-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The Q-allyl-o-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+ )-A, jV-dicyclohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ec[72]. 

Amino acids are the main components of proteins. Approximately twenty amino acids are common constituents of proteins (1) and are called protein amino acids, or primary protein amino acids because they are found in proteins as they emerge from the ribosome in the translation process of protein synthesis (2), or natural amino acids. In 1820 the simplest amino acid, glycine, was isolated from gelatin (3) the most recendy isolated, of nutritional importance, is L-threonine which was found (4) in 1935 to be a growth factor of rats. The history of the discoveries of the amino acids has been reviewed... 

Alkylation of protected glycine derivatives is one method of a-amino acid synthesis (75). Asymmetric synthesis of a D-cx-amino acid from a protected glycine derivative by using a phase-transfer catalyst derived from the cinchona alkaloids (8) has been reported (76). 

The amino acids are usually divided into three different classes defined hy the chemical nature of the side chain. The first class comprises those with strictly hydrophobic side chains Ala (A), Val (V), Leu (L), He (1), Phe (F), Pro (P), and Met (M). The four charged residues, Asp (D), Glu (E), Lys (K), and Arg (R), form the second class. The third class comprises those with polar side chains Ser (S), Thr (T), Cys (C), Asn (N), Gin (Q), His (H), Tyr (Y), and Trp (W). The amino acid glycine (G), which has only a hydrogen atom as a side chain and so is the simplest of the 20 amino acids, has special properties and is usually considered either to form a fourth class or to belong to the first class. 

Fig. 1 Scanning curve of a chromatogram track with 100 ng per chromatogram zone of the amino acids glycine (1), alanine (2), valine (3), leucine (4).

The importance of chemical syntheses of a-amino acids on industrial scale is limited by the fact that the standard procedure always yields the racemic mixture (except for the achiral glycine H2N-CH2-COOH and the corresponding amino acid from symmetrical ketones R-CO-R). A subsequent separation of the enantiomers then is a major cost factor. Various methods for the asymmetric synthesis of a-amino acids on laboratory scale have been developed, and among these are asymmetric Strecker syntheses as well. ... 

Proteins are large biomolecules made up of a-amino acid residues linked together by amide, or peptide, bonds. Chains with fewer than 50 amino acids are often called peptides, while the term protein is reserved for larger chains. Twenty amino acids are commonly found in proteins all are a-amino acids, and all except glycine have stereochemistry similar to that of l sugars. In neutral solution, amino acids exist as dipolar zwitterions. 

Strategy Write the condensation reaction that takes place between glycine and serine. To do this, start with the structural formulas of the two amino acids, glycine at the left, serine at the right. In each case, put the NH2 group at the left, the COOH group at the right. Condense out a water molecule what is left is the structural formula of Gly-Ser. 

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

An application of this method is the enantioselective synthesis of a-amino acids [e.g., (5)-phenyl-glycine (11)]10. Hence, 8 can be regarded as a chiral synthetic equivalent of a carboxyl group. 

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... 

The amino acid glycine, a neurotransmitter at inhibitory synapses throughout the central nervous system (CNS),... 

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