Evaluation of the enantiomeric selectivity in the chiral ligand-exchange chromatography of amino acids by a computational model

The chromatographic resolution of enantiomeric amino acids is accomplished on a reversed phase column using aqueous mobile phase containing the chiral reagent N,N-dimethyl-S-phenylalanine-Cu(II). The separation is a result of the whole interaction between the diastereomeric complex surface and the mixed stationary phase realized by the dynamic coating of the RP-18 carbon chains layer. The elution order seems to be related to the different water coordination capability on copper ion in the formation of the mixed ternary complexes.     

Cyclopropyl-containing sulfonyl amino acids: Exploring the enantioseparation through chiral ligand-exchange chromatography

Russian Journal of General Chemistry - In the scope of a broader study focused on glutamate receptors regulators, we have been engaged in synthesis, analysis and pharmacological characterization of...     

Pressure effects in the planar solidification of a finite slab: convective cooling and prescribed heat flux boundary conditions

Summary The classical Stefan problem assumes a fixed melting temperature. However, when the solid phase is the one with lower density (e.g., water) the solidification of the system causes an overall volume increase that is often contrasted by the container walls. In that case the growing pressure determines a continuous lowering of the freezing point, and the temperature field as well as the interface motion are strongly affected. This paper is concerned with these aspects of the problem; the planar solidification of a slab of finite thickness, contrasted by an opposing elastic force, is numerically simulated. The effects of two different boundary conditions are analysed. When the solidification is driven by convective cooling, the continuous advancement of the melting front is replaced by an asymptotic behaviour, until thermal equilibrium is attained. When the boundary condition is specified in terms of a prescribed heat flow, the melting front velocity is slowed down by a growing adverse temperature gradient. The influence of various parameters on the process is presented and discussed.     

Exploring the metal-catalyzed reaction of furans with alkyl α-diazomethanesulfonate and α-diazomethanephosphonate: synthesis of ω-acyl-substituted sulfono- and phosphonobutadienes

The metal-catalyzed reactions of neopentyl α-diazomethanesulfonate (DAMS) and diisopropyl α-diazomethanephosphonate (DIDAMP) with furan, 2-methylfuran and 2-methoxyfuran are reported. The products consist mostly of ω-acyl-substituted sulfono- or phosphonobutadienes and exo-cyclopropane derivatives. Treatment of the multicomponent reaction mixtures with iodine afforded exclusively the corresponding (E,E)-sulfono- and phosphono-ω-acylfunctionalized dienes, thus providing a short and efficient synthetic route to these hitherto unreported classes of compounds.     

Chiral ligand-exchange separation and resolution of extremely rigid glutamate analogs: 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acids

Owing to their chelation ability, a series of fully constrained l-Glu analogs formed by the spiro-union of two cyclopropane rings (1-aminospiro[2.2]pentyl-1,4-dicarboxylic acids, ASPED A–D), was submitted to chiral ligand-exchange chromatographic (CLEC) analysis. As the initial step, two methodologically different chiral devices were evaluated. A chiral stationary phase (CSP) obtained by dynamic coating of C₁₈ chains with the S-trityl-(R)-cysteine ((R)-STC) was used first with this objective. The lack of separation of the enantiomers of ASPED C and D prompted us to utilize the chiral mobile phase (CMP) prepared from O-benzyl-(S)-serine ((S)-OBS). The latter afforded complete separation of the four pairs of enantiomers. For all the pairs, quantum mechanical investigations shed light on the main features responsible for the different enantiomer recognition mechanism with (S)-OBS. The validated analytical method was then fruitfully adopted for semi-preparative-scale isolation of the enantiomers of ASPED C.     

Spiro[2.2]pentane as a dissymmetric scaffold for conformationally constrained analogues of glutamic acid: focus on racemic 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acids

In search for novel conformationally constrained analogues of L-glutamic acid, a diastereodivergent synthesis of the four 1-aminospiro[2.2]pentyl-1,4-dicarboxylic acid racemic pairs is reported along with their stereochemical assignment, conformational analysis, and preliminary biological evaluation as potential glutamate (ionotropic and metabotropic) ligands.     

Simultaneous diastereo- and enantioseparation of farnesoid X receptor (FXR) agonists with a quinine carbamate-based chiral stationary phase

In the frame of a project aimed at finding non-steroidal farnesoid X receptor (FXR) agonists, we identified 4-(2,4-dimethoxyphenyl)-3,6-dimethyl-1-(2-tolyl)-4,8-dihydro-1H-pyrazole[3,4-e][1,4]thiazepin-7-one (1) as a hit endowed with FXR activity. Most of the compounds synthesised during the hit-to-lead optimisation work were characterised by the presence of two chiral centres and were therefore obtained as mixtures of anti(±)- and syn(±)-diastereoisomers. A restricted sub-set of species harboured with a carboxylic acid group on the distal phenyl ring of the biphenyl (a(±)5 (A1) and s(±)5 (S1)) or the phenoxyphenyl (a(±)6 (A2) and s(±)6 (S2)) moiety at C-4 position of the pyrazole[3,4-e][1,4]thiazepin-7-one core, resulted in suitable diastereo- and enantioresolution with a quinine (QN) carbamate-derived chiral stationary phase (CSP). Differently from the compounds usually analysed with QN-based CSPs, the couples A1/S1 and A2/S2 were atypical selectands, in which the two chiral carbon atoms reside at a remote position with respect to the carboxylic function, the main “point of attack” to the CSP. We produced evidence that the scarcely employed normal-phase (NP) eluent systems represent the elective choice for achieving the simultaneous diastereo- and enantioseparation of this class of compounds over the usually preferred reversed-phase (RP) and polar-organic (PO) modes of elution. Indeed, after the optimisation of the eluent composition, NP conditions allowed to obtain profitable enantioselectivity profiles, along with excellent diastereoselectivity levels (α(A1)?=?1.07, R _S(A1)?=?1.15; α(S1)?=?1.09, R _S(S1)?=?1.47; α(A2)?=?1.08, R _S(A2)?=?1.31; and α(S2)?=?1.06, R _S(S2)?=?1.18). The optimised NP methods are suitable for simultaneously providing information on the diastereo- and enantiopurity of the investigated compounds.

Exploring the synthetic versatility of the Lewis acid induced decomposition reaction of α-diazo-β-hydroxy esters. The case of ethyl diazo(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate

Ethyl diazo(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate was prepared by aldol-type condensation of ethyl diazoacetate with isatin. A systematic and mechanistic study on the Lewis acid induced decomposition reaction of this valuable diazo precursor was carried out with the aim to gain new insights into the mechanistic aspects of the reaction as well as to further understand the factors and experimental conditions which affect the relative product distribution. The reaction, which may proceed via cationic and noncationic mechanisms, was found to be significantly influenced by the reaction environment determined by the characteristics of the Lewis acid employed, by the ability of the Lewis acid to form a complex with the alcohol functionality of the α-diazo-β-hydroxy ester, and by the polarity and nucleophilicity of the solvent used.     

A calibration procedure for center of rotation estimation in ultrasound tomography without position sensor

Experimental Techniques -     

L-Vinylglycine from L-Homoserine.

A simple and practical synthesis of L-vinylglycine starting from L-homoserine is described.