A stereodivergent approach to chiral nonracemic N-protected alpha,alpha-dialkylated amino acids

Menthyl carboxaldehyde is used as a chiral auxiliary to make quaternary amino acids of either configuration via a stereodivergent approach that includes an SN2' displacement by a cuprate reagent and a Curtius rearrangement as key steps.     

Reversed-phase planar chromatography of some enantiomeric amino acids and oxazolidinones

The resolution of two enantiomeric amino acids and four structurally related oxazolidinones was evaluated by reversed-phase planar chromatography using both home-made microcrystalline cellulose triacetate (MCTA) layers and mobile phase additivies, such as beta-cyclodextrins (beta-Cy), modified alpha, beta, gamma cyclodextrins and bovine serum albumin (BSA), on commercially available RP-18W/F254 and SilC18-50/UV254 plates. All the enantiomers were partially or baseline resolved by at least one of the chiral phases tested. Densitograms of optical antipodes and their mixtures were measured on MCTA layers developed with hydroalcoholic solvents.     

Direct determination of enantiomeric purity of FMOC amino acids with high performance liquid chromatography

Summary Analytical methods are described which allow a direct determination of enantiomeric purity of seventeen FMOC amino acids commonly used in peptide synthesis. The corresponding ester derivatives can be separated directly on cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel-OD). The methods are suitable for primary as well as secondary FMOC amino acids. The presence of a highly sensitive fluorescence moiety within the molecule, in combination with large separation factors (-values between 1.5–2.2) allowed for a general detection limit below 0.05%. In several cases the antipode has been determined in the ppm-range. An interesting result has been observed with respect to the elution order of the FMOC amino acid esters. The elution order of the Trp enantiomers is opposite to that obtained with the other amino acids. This is contrary to the generally held belief that elution order is identical within a homologous series of racemates when chromatographed under identical conditions on the same chiral stationary phase. In addition, the inversion of elution of the Pro enantiomers depending on the estertype indicates a competition of different separation mechanisms.     

A stereodivergent asymmetric approach to difluorinated aldonic acids

A (bromodifluoromethyl)alkyne has been deployed in a stereoselective route to difluorinated aldonic acid analogues, in which a Sharpless asymmetric dihydroxylation reaction and diastereoisomer separation set the stage for phenyl group oxidation.     

Determination of enantiomeric purity in biogenic11C-labelled amino acids by aminoacylation of tRNA

In syntheses of naturally occurring amino acids labelled with short-lived radionuclides, such as¹¹C, the determination of the enantiomeric purity presents problems. The aminoacyl coupling of L-amino acids to tRNA followed by a separation with gel filtration of the tRNA-amino acid complex and free amino acid, was here shown to be an adequate method for determining the enantiomeric purity of [methyl-¹¹C]-methionine even in the pmol range. This method has also been used for the determination of the specific radioactivity of the¹¹C-labelled methionine. The method is probably valid for other naturally occurring amino acids and it might also be of interest for enantiomeric separations of L- and D-amino acids of high specific radioactivity.     

Recognition of vinification technology through gas chromatographic data on enantiomeric purity of free amino acids

Analysis of D-amino acids in food, a matter of growing interest due to nutritional implications, has been used as a tool for food evaluation, detection of falsifications and as a genuinity parameter. The evolution of free D-amino acids in wines of a portuguese Vitis vinifera variety (Roupeiro white), bottled during the period 1978–1989 is studied by means of chiral high resolution gas chromatography. D-Ala, D-Val, D-Thr, D-Leu, D-Ser, D-Asx, D-Met, D-Phe, and D-Glx are present in most of the analyzed wines. It was not possible to correlate the evolution of the D/L ratio to the age of the wine. However, a clear correlation between enantiomer purity profiles and the vinification technique could be established. The results show that free D-amino acids may be used as markers for the biotechnological process used in vinification.Dedicated to Professor Dr. Dr. h.c. mult. J.F.K. Huber on the occasion of his 70th birthday     

Stereocontrolled asymmetric synthesis of alpha-hydroxy-beta-amino acids. A stereodivergent approach

The stereocontrolled asymmetric synthesis of alpha-hydroxy-beta-amino acids has been investigated via the Lewis acid-promoted cyanation of (5R,6S)-2-acetoxy-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazines with trimethylsilyl cyanide. Base-catalyzed hydrolysis of the resulting cyano compounds proceeds with excellent stereoselectivity, providing access to diastereomerically pure oxazine-2-carboxylic acids which were readily converted to each enantiomer of the alpha-hydroxy-beta-amino acids isothreonine and nor-C-statine.     

A regio- and stereodivergent synthesis of vic-amino alcohols

A regio- and stereodivergent synthesis of vic-amino alcohols starting from vinylepoxides is described. The developed strategy focuses on the propensity of vinylepoxides and vinylaziridines to be ring-opened at the allylic position by suitable nucleophiles and makes use of reactions that perform such tasks selectively with either retention or inversion of configuration.     

A stereodivergent approach to substituted 4-hydroxypiperidines

A stereodivergent route toward both diastereomeric forms of functionalized 4-hydroxypiperidines has been successfully developed. This route involves biocatalytic generation of the enantiopure starting materials followed by functionalization via N-acyliminium ion-mediated CC-bond formation.     

Determination of enantiomeric excess and concentration of unprotected amino acids, amines, amino alcohols, and carboxylic acids by competitive binding assays with a chiral scandium complex

A practical UV-vis sensing method for enantioselective microanalysis of unprotected amino acids, amines, amino alcohols, and carboxylic acids in aqueous solution has been developed. Both concentration and enantiomeric composition of a wide range of chiral substrates can be determined with high accuracy by two simple competitive binding assays using a scandium complex derived from 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene N,N'-dioxide.     

A regio- and stereodivergent route to all isomers of vic-amino alcohols

Vicinal amino alcohols are substructures in several important natural products. They are also frequently employed ligands in asymmetric synthesis. Many enantioselective syntheses of vic-amino alcohols have been reported, but each structure has required its own synthetic route. This study presents a synthetic strategy leading to all eight possible isomers of a given beta-amino alcohol, starting from vinyl epoxides. The developed strategy focuses on the propensity of vinyl epoxides and vinylaziridines to be selectively ring-opened at the allylic position by suitable hard nucleophiles. Within this strategy, a novel large-scale aminolysis reaction and the synthesis of a trisubstituted N-H vinylaziridine are detailed.     

TLC resolution of enantiomeric mixtures of amino acids

Summary Resolution of enantiomeric mixtures of DL-amino acids (Nine) using silica gel layers impregnated with (-)-bruncine is reported. The solvent system used was Butanol: Acetic acid: Chloroform (3∶1∶4). The diastereomers were formed and hydrolysed, by dilute HCl spray, on the chromatogram only and the amino acids thus resolved were located by ninhydrin spray. The cross resolution possibilities of enantiomers were also calculated.     

Catalyst control in sequential asymmetric allylic substitution: stereodivergent access to N,N-diprotected unnatural amino acids

The sequential use of Cu-catalyzed asymmetric allylic alkylation, olefin cross-metathesis, and Ir-catalyzed asymmetric allylic amination allows the concise, stereodivergent synthesis of complex chiral amines with complete regiocontrol and good diastereoselectivity, exemplified by the synthesis of a pair of diastereoisomeric unnatural branched amino acid derivatives.     

Determination of absolute configuration and enantiomeric purity of spirocyclic alcohols by 1h nmr

Absolute configuration and enantiomeric purities of some hydroxy-ketones and diols of spiro[4.4]nonane and 2,2′-spirobi-indan can be simultaneously determined by use of MTPA derivatives and a lanthanoid shift reagent.     

Synthesis of enantiopure cyclobutane amino acids and amino alcohols

(−)-(1R,3S)-3-Amino-2,2-dimethylcyclobutanecarboxylic acid and (+)-(1R,3S)-3-amino-2,2-dimethylcyclobutylmethanol, which can be used to prepare enantiopure oligopeptides and cyclobutane-based carbocyclic nucleosides, were synthesized from (+)-(1R)-α-pinene.