Absolute configuration amino acids

Polypeptides. These are a string of a-amino acids usually with the natural 5(L) [L-cysteine is an exception and has the R absolute configuration] or sometimes "unnatural" 7f(D) configuration at the a-carbon atom. They generally have less than -100 amino acid residues. They can be naturally occurring or, because of their small size, can be synthesised chemically from the desired amino acids. Their properties can be very similar to those of small proteins. Many are commercially available, can be custom made commercially or locally with a peptide synthesiser. They are purified by HPLC and can be used without further purification. Their purity can be checked as described under proteins. 

What is the absolute configuration (R or S) at the a-carbon atom in each of the following i-amino acids ... 

Absolute configurations of the amino acids are referenced to D- and L-glyceraldehyde on the basis of chemical transformations that can convert the molecule of interest to either of these reference isomeric structures. In such reactions, the stereochemical consequences for the asymmetric centers must be understood for each reaction step. Propose a sequence of reactions that would demonstrate that l( —)-serine is stereochemically related to l( —)-glyceraldehyde. 

In spite of the former widespread use of d and l to denote absolute configuration, the method is not without faults. The designation of a particular enantiomer as d or l can depend on the compounds to which it is related. Examples are known where an enantiomer can, by five or six steps, be related to a known d compound, and by five or six other steps, be related to the l enantiomer of the same compound. In a case of this sort, an arbitrary choice of d or l must be used. Because of this and other flaws, the DL system is no longer used, except for certain groups of compounds such as carbohydrates and amino acids. 

If the proton-donating ability of the amino acid at 188 is weaker, then the enantioselectivity of the reaction will be reversed compared to that of native enzyme. As shown in Table 3, the absolute configuration of the products by this mutant is opposite to those of the products obtained by the native enzyme and the ee of the products dramatically increased to 94 and 96%, respectively. This inversion of the enantioselectivity of the reaction supports the reaction mechanism that the Cys 188 of the native enzyme is working as the proton donor to the intermediate enolate form of the product. ... 

The absolute configuration of koumine has also been confirmed by a biomimetic synthesis of koumine from vobasine (50) (43). The configuration was correlated with L(—)-tryptophan, since vobasine was reduced to drega-mine (51) and the latter had been synthesized from L(—)-tryptophan with conservation of the (S) configuration of the amino acid, which corresponds to C-5 of koumine (44). 

The relative stereochemistry of stephadiamine (16) was clarified by X-ray diffraction analysis, using the direct method, and the absolute configuration was solved by the heavy-atom method, using the N-p-bromobenzoyl derivative (6). Stephadiamine (16), a C-norhasubanan alkaloid, is not regarded as a hasubanan congener in the strict sense, but as a new member of oe-amino acid derivatives (6). 

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. 

WIN 64821 (10) and (—)-ditryptophenaline (11) syntheses [7], not only effectively differentiated the two amide moieties but also most importantly marked the first in a series of stereochemical transfer steps in which the stereochemistry of the constituent L-amino acids was relayed to ultimately define each of the relative and absolute stereochemical configurations at all eight stereogenic centers found in the target compound. Finally, /V-methylation of the base-sensitive amide in 77 % yield using methyl iodide and potassium carbonate in acetone completed the 5-step synthesis of our key tetracyclic bromide monomer starting from commercially available amino acid derivatives. 

Kowalik, J. Sawka-Dobrowolska, W., and Glowiak, T., Synthesis, molecular structure, and absolute configuration of an optically active (l-amino-2-phe-nylethyl)phosphonic acid monohydrate, J. Chem. Soc., Chem. Commun., 446, 1984. 

Cucurbitine (47) is the active principle from the seeds of Cucurbita moschata Duch., which are used in Chinese folk medicine. The structure of this unique a-amino acid was established through a combination of chemical and spectroscopic techniques (81, 82). A single-crystal X-ray analysis of the perchlorate of cucurbitine has confirmed the original hypothesis and has established the absolute configuration of 47 (83). 

In another legume, Afzelia bella Harms (Caesalpinoidene), the same authors have isolated the new rrfree amino acids. The structure of the diacid 54 is based on mass, H, and l3C-NMR spectroscopy (95) the proposed absolute configuration of 54 was also demonstrated by X-ray diffraction (96). Compound 54 is probably identical with the diacid independently isolated from the red alga Chondria coerulescens (Crouan) Falk. (Rhodomelaceae) (97). 

The a-carbon of all amino acids, with the exception of glycine, has four different substituent groups and is therefore an asymmetric carbon atom. Such an atom can exist in two different spatial arrangements which are mirror images of each other. These structural forms of molecules are known as stereoisomers and the common notation of D and L forms is used, a nomenclature that refers to their absolute spatial configuration when compared with that of glyceraldehyde (Figure 10.4). 

Figure 10.4 The stereochemical relationship between amino acids and glycer-aldehyde. The designation of d or l to an amino acid refers to its absolute configuration relative to the structure of d- or L-glyceraldehyde respectively. The d and l forms of a particular compound are called enantiomers.

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. 

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