Amino acids enantiomeric forms

Thus, it is possible that amino acids were first produced in a probiotic system. A slight enantiomeric imbalance in these amino acids might have been created by the action of some naturally occurring physical factors such as CPL. Alternatively, the imbalance might have been created in the presence of some physical factors at the time when these amino acids were formed. This imbalance might then have been amplified in other asymmetric reactions catalyzed by... 

For the tris(amino acidato)metal(III) complexes four geometrical and chiral isomers are possible, as shown in Scheme 2, where NO is the chelated amino acid anion, mer and fac refer to the meridional and facial geometrical isomers and A and A refer to the configuration at the metal centre. For the glycine complexes A and A are an enantiomeric pair, while for the optically pure forms of the other amino acids they form a diastereomeric pair and hence are easier to separate. For most of the simple bidentate amino acids of the kinetically inert metal ions Cr" , Co " and Rh ", the four isomers have been obtained. The isomers are distinguishable by their UV/visible, CD and NMR spectra. Not all the isomers can be found in certain cases, for example, with L-proline the k-fac isomer could not be prepared, a fact which was predicted on steric grounds." ... 

In 1984, a new reagent, l- luoro-2,4-dinitrophenyl-5-L-alanine amide (FDAA), was reported by Marfey for the enantiomeric separation of amino acids [37]. FDAA contains the enantiomerically pine L-alanine moiety in the reagent and reacts with amino acids to form diastereomers (Figure 6.5). As of now, many Marfey reagent analogs have been reported... 

Effects of L- -amino acid ligands - Stepping on the tail of enantioselectivity The naturally occurring -amino acids form a class of readily available strongly coordinating ligands, which exhibit broad stmctural variation. Moreover, their availability in enantiomerically pure form offers opportunities for enantioselective catalysis. Some derivatives of these compounds have been... 

The four stereoisomers of this amino acid include the D- and L-forms of a-methylisoleucine and a-methylalloisoleucine. Cronin, J.R., and Pizzarello, S., 1997. Enantiomeric excesses in meteoritic amino acids.. Science 275 951—955. 

The use of enantiomerically pure (R)-5-menthyloxy-2(5.//)-furanone results in lactone enolates, after the initial Michael addition, which can be quenched diastereoselectively trans with respect to the /J-substituent. With aldehydes as electrophiles adducts with four new stereogenic centers arc formed with full stereocontrol and the products are enantiomerically pure. Various optically active lactones, and after hydrolysis, amino acids and hydroxy acids can be synthesized in this way317. 

The iodoalanine derivative is available in both enantiomeric forms and this method offers an extremely simple route to large numbers of non-natural amino acids.4 Therefore a reliable and practical method for the synthesis of fully protected iodoalanine 3 in a multigram scale is highly desirable. 

Although these Boc derivatives underwent methylation with poor selectivity (compared to 3-amino-N-benzoyl butanoates [106] and Z-protected methyl 4-phen-yl-3-aminobutanoate [107]), epimers were succesfully separated by preparative HPLC or by flash chromatography. However, saponification of the methyl ester caused partial epimerization of the a-stereocenter and a two-step (epimerization free) procedure involving titanate-mediated transesterification to the corresponding benzyl esters and hydrogenation was used instead to recover the required Boc-y9 -amino acids in enantiomerically pure form [104, 105]. N-Boc-protected amino acids 19 and 20 for incorporation into water-soluble /9-peptides were pre-... 

Compared to synthetic catalysts, enzymes have many advantages. First of all, being natural products, they are environmentally benign and therefore their use does not meet pubhc opposition. Enzymes act at atmospheric pressure, ambient temperature, and at pH between 4 and 9, thus avoiding extreme conditions, which might result in undesired side reactions. Enzymes are extremely selective (see below). There are also, of course, some drawbacks of biocatalysts. For example, enzymes are known in only one enantiomeric form, as they consist of natural enantiomeric (homochiral) amino acids their possible modifications are difficult to achieve (see Section 5.3.2) they are prone to deactivation owing to inappropriate operation parameters and to inhibition phenomena. 

A similar reaction occurs with 2-methylcyclopentane-l,3-dione,176 and can be done enantioselectively by using the amino acid L-proline to form an enamine intermediate. The (S)-enantiomer of the product is obtained in high enantiomeric excess.177... 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

The question was whether impurities were present in the samples analysed (Bada et al., 1983). In a more recent publication, Cronin and Pizzarello (1997) reported amino acid analyses using Murchison material in which an excess of L-enantiomers was present. Contamination with terrestrial biological material can be ruled out, as the amino acids in question are not proteinogenic a-methylamino acids, which occur either extremely seldom or not at all in terrestrial life forms, were detected. GLPC/mass spectrometry (MS) analysis gave the following enantiomeric excess (ee) values ... 

Such enantiomeric excesses have not been observed in analyses of the corresponding a-H-a-aminoalkanoic acids. According to the authors, the excess of the L-forms could be due to a partial photocleavage of the racemic amino acid mixture as a result of the influence of circularly polarized UV light in a presolar cloud (Cronin and Pizzarello, 2000). 

The question also arises as to where the chiral molecules came from. Were the L-amino acids or the D-sugars selected on the primeval Earth, or are exuaterresuial sources responsible for the homochirality This second possibility is dealt with by hypotheses on the effect of circularly polarised light, of extraterrestrial origin, on chiral molecules in the molecular clouds from which the solar system was formed. One such hypothesis was proposed by Rubenstein et al. (1983) and developed further by others, particularly A. W. Bonner (Bonner and Rubenstein, 1987) both scientists worked at Stanford University. The authors believe that the actual radiation source was synchrotron radiation from supernovae. The excess of one enantiomeric form generated by this irradiation process would have needed to be transported to Earth by comets and meteorites, probably during the bombardment phase around 4.2-3.8 billion years ago. 

It is still unclear what kind of radiation sources can lead to asymmetric reactions. Jeremy Bailey from the Anglo-Australian Observatory in Epping, Australia, investigated which astronomical objects could be considered radiation sources (Bailey et al., 1998 Bailey, 2001). It was possible in laboratory experiments to generate a small enantiomeric excess of some amino acids by using circularly polarized UV light (Norden, 1977). This asymmetric photolysis involves photochemical decomposition of both d- and L- enantiomers, but at different rates, so the more stable form tends to survive. This process must be subject to autocatalytic multiplication. 

Ai-Stearoylamino acids and their methyl esters were synthesized from enantiomeric and racemic forms of tyrosine, serine, alanine, and tryptophan (Fig. 16). Analogs of these molecules were investigated initially over 30 years ago by Zeelen and Havinga, who found stereochemical differentiation in the monolayer HjA isotherms of these materials (Zeelen, 1956 Zeelen and Havinga, 1958). We have extended this study using more sensitive Langmuir balances, a wider array of dynamic and equilibrium techniques, and the A-stearoyl methyl esters of the amino acids (Harvey et al., 1989 Harvey and Arnett, 1989). 

The 1,3-dipolar cycloaddition of nitrile oxides and 2-methylfuran provides suitable precursors for a-amino acids such as L-furanomycin 448 that contains a dihydrofuran ring (495). By using a chiral nitrile oxide derived from mannitol bis(acetonide), the enantiomerically pure furoisoxazoline 449 has been obtained. Hydroboration-oxidation of the latter leads to the hydroxy-substituted annulated THF derivative 450, which is converted via dihydrofuran 451 to furanomycin 448 in enantiomerically pure form (Scheme 1.55). 

Asymmetric syntheses of (3- amino acids result from the addition of chiral enolates (399) to nitrone (400) via A-acyloxyiminium ion formation (642, 643). Regioselective convergence is obtained in the reactions of chiral boron- and titanium- enolates (399a,b), (401), and (402). This methodology was used in preparing four stereoisomers of a-methyl- 3-phenylalanine (403) in enantiomeric pure form (Scheme 2.179) (644). 

Complexation of an amino acid derivative with a transition metal to provide a cyanation catalyst has been the subject of investigation for some years. It has been shown that the complex formed on reaction of titanium(IV) ethoxide with the imine (40) produces a catalyst which adds the elements of HCN to a variety of aldehydes to furnish the ( R)-cyanohydrins with high enantioselectivity[117]. Other imines of this general type provide the enantiomeric cyanohydrins from the same range of substrates11171. 

The amino acid 26, which has been isolated from various Amanita fungi [35], is one of the few examples of a natural product with an achiral allene moiety (Scheme 18.10) and was prepared inter alia by Strecker synthesis and also substitution reactions of allenic bromides and phosphates [36]. Recently, even unfunctionalized allenes have been found in nature seven allenic hydrocarbons 27 with chain lengths ranging from C23 to C31 were isolated from the skin of the Australian scarab beetle Anti-trogus consanguineus and related species (Scheme 18.10) [37]. Also these allenes do not occur in enantiomerically pure form, but with enantiomeric excesses of86-89% ec. 

Extractions of aqueous solutions of racemic amino-acid ester salts with solutions of / -6/s(dinaphthyl)-22-crown-6 [284] in chloroform revealed the dependence of the enantiomeric distribution constant on the structure of the amino acid ester (Table 64). In order to limit the concentrations of complex in the aqueous phase, inorganic salts were added. In the case of tyrosine, serine and alanine no extraction of salt was observed obviously these salts form very hydrophilic complexes. The highest degree of chiral recognition was found with [284] and p-hydroxyphenylglycine methyl ester hexafluorophosphate [A(AG°)... 

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