From a-aminobutyrate

Chiral 1,2,3-oxazaborolidines simply obtained from a-amino acid derived sulfonamides and borane were first applied in Diels-Alder reactions by Taliasu and Yamamoto228, and Helmchen and colleagues229. Yamamoto prepared catalysts from a-aminobutyric acid derived arylsulfonamides and found that the enantioselectivity of the reaction between... 

It should be noted that there is no question that a-ketobutyric acid can be formed from a-aminobutyric acid directly either by deamination or by transamination (see p. 71). 

Cyclic peptide from 11 amino acids. Preparation by fermentation of Tolypocladium inflatum Gams with addition of DL-a-aminobutyric acid to the fermentation medium. Isolation by homogenization of mycelium, extraction with 90 % methanol and column chromatographic purification. 

By means of a procedure described above, Hanson and Fittkau (HI) isolated seventeen different peptides from normal urine. One of them, not belonging to the main peptide fraction, consisted of glutamic acid, and phenylalanine with alanine as the third not definitely established component. The remaining peptides contained five to ten different amino acid residues and some unidentified ninhydrin-positive constituents. Four amino acids, i.e., glutamic acid, aspartic acid, glycine, and alanine, were found in the majority of the peptides analyzed. Twelve peptides contained lysine and eight valine. Less frequently encountered were serine, threonine, tyrosine, leucine, phenylalanine, proline, hydroxyproline, and a-aminobutyric acid (found only in two cases). The amino acid composi-... 

Cyclosporin A contains II amino acids, joined in a cyclic strncture by peptide bonds. The structure is also stabilized by intramolecular hydrogen bonds. Only two of the amino acids, i.e. alanine and valine, are typical of proteins. The compound contains several A-methylated amino acid residues, together with the even less common L-a-aminobutyric acid and an Ai-methylated butenylmethylthreonine. There is one o-amino acid, i.e. o-alanine, and the assembly of the polypeptide chain is known to start from this residue. Many of the other natural cyclosporin structures differ only with respect to a single amino acid (the a-aminobutyric acid residue) or the number of amino acids that have the extra Ai-methyl group. 

This dual activity against both nematode and arthropod parasites of animals was an unexpected bonus from a screen for anthelmintic agents. The reason for this broad activity lies in their mode of action. They act by interfering with y-aminobutyric acid (GABA) mediated neurotransmission. When treated with avermectin, the nematode Ascaris suum becomes paralyzed although it retains normal muscle tone (17). Picrotoxin, an antagonist of GABA, can reverse the effect of avermectin on neurotransmission vitro. 

The Pd-catalyzed amidocarbonylation was used for the synthesis of a-arylglycines that are antimicrobial agents and enzyme inhibitors.Thus, iV-acyl-a-arylglycines and other iV-acyl-a-amino acids were synthesized in highly efficient and economical manner under the standard conditions. In a similar manner, an advanced intermediate for the synthesis of antiepileptic Levetiracetam 7, iV-acetyl-a-aminobutyric acid 6, was synthesized in high yield from propanal and acetamide (Equation (1)). ... 

Despite the fact that solvent effects on enzyme enantioselectivity appear to resist our efforts to rationalize their outcome using commonly accepted solvent descriptors, the effects are certainly there. An impressive example is provided in a report on the successful resolution of ds/trans-( 1 R,5 R)-bicyclo[3.2.0]hept-6-ylidene-acetate ethyl esters, intermediates in the synthesis of GABA (y-aminobutyric acid) analogs, by the Pfizer Bio transformations and Global R D groups (Scheme 2.2) [136]. From a screening protocol, CaLB was identified as a reactive catalyst for the hydrolysis of the racemic mixture of / //-os lor enantiomers with approximately equal activity for the ds- and tmns-isomers and a rather modest (E = 2.7) preference for the /Z-(lR,5R)-enantiomers. Application of medium engineering resulted in a phenomenal increase in the enantioselectivity (addition of 40% acetone, E > 200), while the ds- and trans-isomers were still converted at an almost equal rate. 

This methylation procedure is quite generally satisfactory for simple primary and secondary amines. For methylation of a secondary amine only half as much formaldehyde is required, although a larger amount does no harm. The submitters also have prepared, in uniformly good yields, benzyldodecylmethylamine (b.p. 180-182°/4 mm.) from benzyldodecylamine, and a-amyl-hexyldimethylamine (b.p. It5°/16mm.) from a-amylhexylamine. It is reported 2 that the reaction can be successfully applied to the methylation of butylamine, benzylamine, tetramethylenediamine, piperidine, and phenyl-a-aminobutyric acid. 

FIGURE 7 Effect of pH on the chiral resolution of a-aminobutyric acid on the Spherisorb ODS-2 column using water as the mobile phase containing (a) Cu(II)-L-proline (4 mM) and (b) Cu(II)-L-methylphenyl alanine as CMPAs separately and respectively (from Ref. 55). 

The second major metabolite from T. inflation is structurally closely related to cyclosporin A, as can be deduced by elemental analysis, mass spectrum (m/z 1217), IR and NMR spectra. Furthermore, the presence of the double bond and OH group of the unusual MeBmt was established. Sulphonic acids in methanol or dioxane effected the typical rearrangement reaction by N, O-acyl migration to the iso-compound (13). Hydrolysis furnished the same amino acids as cyclosporin A with the exception of L-a-aminobutyric acid, which is replaced in cyclosporin C (12) by L-threonine. The amino-acid sequence could be deduced by conversion of cyclosporin C into cyclosporin A via the corresponding tosylate (14) and iodo derivatives (15) [7]. Position 2 for L-threonine as well as the assumed twisted -pleated sheet conformation of the molecule were confirmed by 13C-NMR spectra. 

Figure 2 Order and organization of enniatin synthetase and cyclosporin synthetase as deduced from gene sequence and biochemical characterization. Symbols in the adenylateforming modules (black boxes) indicate the corresponding activated amino acids. M stands for A -methyltransferase domain. Condensation domains are represented by white boxes. (A) Top Structure of enniatin synthetase. EA represents the D-Hiv-activating module EB represents the L-valine-activating module D-Ehv is D-2-hydroxyisovaleric acid. Bottom Structural features of the wild-type A -methyltransferase domain M of esynl. The black boxes indicate conserved motifs which can be found within methyltransferases and A -methyltransferase domains of peptide synthetases (see also Fig. 3). The numbers indicate the amino acid position in the sequence of Esyn. (B) Structure of cyclosporin synthetase. Abu = L-a-aminobutyric acid Bmt = (4A)-4-[(E)-2-butenyl]-4-methyl-L-threonine.

Figure 6.8 Experimental variation of the retention of 23 phenylthiohydantoin (PTH) derivatives of amino acids with mobile phase composition in RPLC. Mobile phase mixtures of acetonitrile and 0.05M aqueous sodium nitrate buffer (pH — 5.81). All mobile phases contain 3% THF. Stationary phase ODS silica. Solutes D = aspartic acid C-OH = cysteic acid E = glutamic acid N = asparagine S = serine T = threonine G = glycine H = histidine Q = glutamine R = arginine A = alanine METS = methionine sulphone ABA = a-aminobutyric acid Y = tyrosine P = proline V = valine M = methionine NV = norvaline I = isoleucine F = phenylalanine L = leucine W = tryptophan K = lysine. Figure taken from ref. [610]. Reprinted with permission.

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