Amino acids absolute configuration determination

Thus, we have developed a method for the detection of the absolute configuration of amino acids with low enantioenrichment. We thought that the absolute configuration of amino acids can be determined by detecting the absolute configuration of the produced pyrimidyl alkanol with high enantiomeric excess by asymmetric autocatalysis using amino acids as chiral initiators (Scheme 18). 

Because of the biological importance of many chelating organic molecules such as a-amino acids many of their absolute configurations (determined by the Bijvoet method (57)), are available. This means that the known absolute configuration of one centre in a molecule can be used to deduce that of other centres. This can be done in several ways, and has proved extremely useful in coordination chemistry. 

Glycinocins A, B, C and D were discovered by F. Kong and G. T. Carter in 2003, and were isolated from the fermentation broth of an unidentified terrestrial actinomycete species. The absolute configurations of the amino acid residues were determined by Marfey s methodology l... 

Another early observation of helical structures is that on a number of 2-hydroxy-dodecyl amino acid derivatives 64a-d. The absolute configuration of the chiral carbon atom in the side chain, which was introduced by nucleophilic opening of 1,2-epoxydodecane by the amino group of the amino acid, was not determined in this study. The Trp derivative 64a gave rod-like aggregates regardless of the... 

NMR can be a powerful tool for determination of enantiomeric excess or absolute configuration of the optically active compounds, however, these processes require the use of some auxiliaries, for example, chiral lanthanide shift reagents or chiral derivatising agent. In many cases, the starting point for determination of enantiopurity of amines, amino acids or diols is the formation of chiral imines. 

This report presents various methods developed primarily at our laboratory for chromatographic resolution of racemates of several pharmaceuticals (e.g., -blockers, NSAIDS, anta-acids, DL-amino acids, Bupropion, Baclofen, Etodolac, Carnitine, Mexiletine). Recently, we developed methods for establishing molecular dissymmetry and determining absolute configuration of diastereomers (and thus the enantiomers) of (/< .S )-Baclofcn, (/d.SJ-Bctaxolol with complimentary application of TLC, HPLC, H NMR, LCMS this ensured the success of diastereomeric synthesis and the reliability of enantioseparation. 

Starting from the Michael adducts of (4R,5S)-4,5-diphenyloxazolidine-2-one (100) onto chlorospiropentylideneacetates 2 c (102c-Bn and 102c-Me) and juggling with the set of transformation discussed above, the spiropentane amino-carboxylic acids 207,208 and 213 were also prepared either in racemic (208) or enantiomerically pure (207, 213) forms, the absolute configurations of which were determined on the basis of X-ray crystal structure analysis of the precursor... 

Scheme 6.66 Products of the 12-catalyzed asymmetric Michael addition of a-alkyl cyanoacetates to vinyl sulfone and exemplary conversion of one adduct to the respective 3 amino acid. The values in parentheses were obtained after single recrystallization the absolute configurations of the products were not determined.

Scheme 6.92 Product range of the 79-catalyzed Michael addition of a-aryl cyanoacetates to phenyl vinyl sulfone and conversion of one exemplary adduct (R = Ph) to the corresponding protected 3-amino acid. The absolute configurations of the adducts were not determined.

As described in the section dealing with liquid chromatographic methods, the reaction of 0,0-di-substituted tartaric anhydrides with racemic amino alcohols in acidic solution leads exclusively to the corresponding diastereomeric monoesters, which are easily separated by reversed-phase HPLC. However, H- and sometimes 13C-NMR spectra of these compounds are in many cases also highly useful for determining the diastereomeric ratio and in many cases the absolute configuration. 

For example, on reaction with (S)-jV-(methylsulfonyl)phenylalanyl chloride, meso-2-cy-clopentene-l,4-diol yields, besides the diester, the two diastereomeric monoesters which are separated chromatographically95. Since the absolute configuration of the amino acid moiety is known, it is (in principle) sufficient to determine the relative configuration at the three stereogenic centers in the monoesters, e.g., by an X-ray analysis (see p 473 for assignment by chemical correlation). 

Related to this is the use of amino acid derived reagents for resolution of racemic carbonyl compounds and determination of absolute configurations by X-ray analysis at the imine stage. This is exemplified by the L-valinol derived imine of tricarboxyl (l-formyl-2-methoxyphenyl) chromium (see p 417)88. 

The dysideathiazoles A-E (331-335) are a series of polychlorinated amino acid derivatives from Pacific Island collections of D. herbacea. The structures were determined by X-ray analyses and the absolute configurations were determined by X-ray crystallography of a brominated derivative [301]. Herbamide A (336), a chlorinated amide was isolated from a Papua New Guinean sample of D. herbacea as a minor component [302]. D. herbacea from the southern Great Barrier Reef contained a thiazole (337) amongst other known metabolites [303]. A Dysidea sp. 

Azetidine-2-carboxylic acid (2) like proline gives an intense blue color with sodium nitroprusside in 10% acetaldehyde solution in the presence of sodium carbonate. 98,99 Upon usual acid hydrolysis (6M HC1, 110 °C, 24 h or more) as required for amino acid analysis, azetidine-2-carboxylic acid is completely decomposed, yielding mainly homoserine lactone, as well as other ninhydrin-positive compounds. 87,89,99 To enable an accurate quantification of this imino acid, azetidine-2-carboxylic acid peptides should be hydrolyzed by alkali (5M barium hydroxide, at 100 °C for 18 h 89 or 2 M sodium hydroxide at 110°C for 22h 100 ). There are extensive NMR spectroscopic data available 100-104 and the absolute configurations of A-acetyl-L-azetidine-2-carboxylic acid 105 and A-terf-butoxycarbonyl-L-azetidine-2-car-boxylic acid 106 have been determined by X-ray analysis. 

Stabilization is maintained by several hydrogen bonds. Interesting details include a single m-amide linkage between MeLeu-9 and MeLeu-10. Furthermore, the L-configuration of MeBmt-1 was confirmed and the still unknown partial sequence of residues 7 and 8 was determined as L-alanine-D-alanine. The absolute configuration of iodocyclosporin A and hence that of cyclosporin A were deduced from the reliable identification of the L-amino-acid residues. 

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