Enantiomer最新文献

In contrast to what is often expressed in the literature, reversible and irreversible solid(s)-solid(s) transitions in binary system of non-racemizable enantiomers are not always referred to as polymorphism. Order-disorder phenomena, miscibility gaps with critical temperatures and transitions in which three-phases or even four-phases are involved can also occur. In the case of reversibility, three-phase invariants such as eutectoid or peritectoid corresponding to the reversible formation or decomposition of racemic compounds are described. The heterogeneous equilibria are reviewed with or without miscibility in the solid state. Several four-phase invariants and order-disorder transitions are predicted.

A small amount of water present in a normal phase chiral HPLC with a Chiralcel OD column was found to be critical and necessary to separate a pharmaceutical chiral intermediate, 3-piperidineacetamide analogue. The amount of water in the normal mobile phase was optimized, and a likely mechanism of the separation was proposed.

The history of the discovery and some benchmark achievements of enantioselective ligand exchange chromatography (LEC) are briefly reviewed. Some of the most important results of investigations into the structure of Cu(II) complexes with nitrogen-substituted alpha-amino acids are summarized, and the role of water molecules that are coordinated in two axial positions of these complexes in the mediation of between-ligand interactions is underlined. UV and circular dichroism spectroscopy are shown to be very convenient for studying and quantifying the thermodynamic and kinetic enantioselectivity phenomena in the complex formation. Polystyrene-based chiral ligand exchange resins served as the first highly selective column packing in the development of enantioselective liquid chromatography. These resins were then followed by more efficient silica bonded monomeric and polymeric HPLC phases. The latter proved to be especially stable in aqueous media at elevated temperatures. Finally, chiral coated ligand exchanging RP phases presented the most inexpensive, but highly efficient and selective phases for the resolution of chelate-forming racemic solutes in LC and TLC. The mechanism of chiral resolution on these last phases involves an essential interaction of both the selector and selectand with the achiral hydrophobic surface. The same is valid for chiral resolutions according to chiral mobile phase techniques. Perspectives on further development of enantioselective LEC are discussed.

The reaction mixture obtained by treating equimolar amounts of a TADDOL with lithium triethylborohydride promotes the catalytic enantioselective Michael addition of malonates to chalcone with good yields and moderate enantioselectivities. The catalyst is alternatively generated reacting the 1,4-diol with butyllithium and triethylborane. The adduct of dibenzyl malonate to chalcone is attained with 99% ee, after one recrystallization. The reaction scale-up was achieved successfully.

Chiromorphology, chirality of morphology (shape), is expressed at all levels in nature from molecules to individual organisms. It is particularly important in the biological world as nucleic acids and proteins of all life forms on Earth employ molecules of a unique invariant handedness. This article briefly outlines chiromorphology at various orders of magnitude, from molecules to organisms, to seek links among them. It also reports and reviews our own work on chirality induction in non-chiral compounds by binding to, or reaction with, chiral compounds in solution as well as in the solid states, and on chiral discrimination in the solid state. For example, chirality induction offered valuable information on DNA-ligand interactions. Achiral molecule adopted a chiral high energy conformation in the solid state which was ideal for an enantioselective reaction. These solid-state specific chiral phenomena were detected by solid-state CD spectroscopy.

The state of art in chiral capillary electrochromatography is reviewed. Chiral separations by capillary electrochromatography were carried out using capillaries packed with chiral stationary phases or achiral stationary phases in combination with a chiral selector added to the mobile phase. Furthermore, the use of open tubular capillaries containing the chiral selector coated to the capillary wall was also reported. Among other separation principles moleculary imprinted polymers represent a challenging approach for chiral capillary electrochromatography. A recent trend is the use of polymeric continuous beds with a chiral selector incorporated.

An evaluation of the use of the Jasco CD-995 in conjunction with achiral high-performance liquid chromatography (HPLC) for the determination of the enantiomeric purity of various SB compounds is described. The Jasco CD-995 is the first commercially-available detector specifically designed for the on-line monitoring of circular dichroism (CD) at a fixed wavelength. Predecessors such as the OR-990 from Jasco and other manufacturers use optical rotation as the detection principle. The results demonstrate that where enantiomeric purity is required to be controlled at levels greater than 99% w/w it is unlikely that the use of the CD-995 with achiral HPLC will compare with the sensitivity of enantio-selective HPLC and capillary electrophoresis (CE). In contrast, where the control of enantiomeric purity is required at levels less than 99% w/w good agreement can be achieved between the CD-995 with achiral HPLC and these techniques. Furthermore, the ability of the CD-995 in such situations to monitor ordinary UV absorbance and CD facilitates the simultaneous measurement of chemical and enantiomeric purity. The benefits in terms of "faster, information-rich analyses" are clear.

Enantiomeric ratio of hyoscyamine from Scopolia extract was determined by chiral HPLC-CD analysis. It was found that circular dichroism (CD) detection allowed the analysis of the sample without any special pretreatment whereas UV detection required an ammonia-ether extraction. To obtain a shorter analysis time for the determination, reversed-phase HPLC-CD analysis was applied by using a g-factor calibration curve (EE% vs. CD/UV). The analysis time was shortened from 35 to 18 min. EE% values obtained were consistent with those by chiral HPLC analysis.

The introduction of a stereogenic centre to produce an "unnatural" amino acid can be accomplished in a variety of ways ranging from asymmetric hydrogenation to biotransformations based on transaminase enzymes. Our transaminase approach can be used to access a wide variety of L- and D-amino acids from an alpha-keto acid substrate. It is run as a whole cell biotransformation and uses coupled enzyme systems. In addition, formation of amino acids with small side chains, such as 2-aminobutyrate, can cause significant isolation problems due to the presence of small amounts of other amino acids, such as alanine. The improvements we have made to the approach are illustrated with 2-aminobutyrate as the example. Aspartic acid is used as the amino donor and gives rise to the formation of pyruvate, a substrate for the transaminase enzymes. We have now developed an alternative approach where lysine is used as the amino donor to allow formation of a cyclic by-product that is removed from the equilibrium.

Synthesis of optically active samples of bromochlorofluoromethane (CHFClBr) was performed via fractional crystallisation of the strychnine salts of bromochlorofluoroacetic acid (FClBrCCO2H). The S-(+) (R-(-)) absolute configuration of the acid was established by X-ray crystallography and the S-(+) (R-(-)) absolute configuration of the haloform was determined using Raman Optical Activity (ROA) and molecular modelling of the enantioselective molecular recognition process of CHFClBr by the chiral cryptophane-C. From these stereochemical assignments it was observed that the decarboxylation used to obtain S-(+)- and R-(-)-CHFClBr from respectively S-(+)- and R-(-)-FClBrCCO2H occurred with retention of configuration. Finally, the first parity violation (PV) test on CHFClBr was performed and yielded an upper bound for this small stereophysical effect.