Enantiomer最新文献

The stereoselective oxidation of dihydrohaloperidols (3a, b) and dihydrobromoperidols (4a, b), which are the main metabolites of haloperidol (1) and bromoperidol (2) in humans, respectively, were pharmacokinetically investigated using human liver microsomes and human cytochrome P450(CYP) isoenzymes expressed in the human cell line. The oxidation rates of the (R)-isomers (3a and 4a) in the human liver microsomes were faster than those of the (S)-isomers (3b and 4b), and the R/S enantiomeric ratios of 3 and 4 for intrinsic clearance (Vmax/Km) were 1.40 and 3.10, respectively, showing that stereoselective oxidation occurred in human liver. Concerning the involvement of the CYP isoenzymes in this oxidative pathway, the (R)-isomers (3a and 4a) were catalyzed by both CYP3A4 and CYP2D6, however, the (S)-isomers (3b and 4b) were catalyzed only by CYP3A4.

Limited studies have been conducted in reversed-phase chiral chromatography despite the relevance to water soluble chiral analytes. Systematic investigation and interpretation of factors affecting chiral separation in reversed-phase LC is crucial to efficient chiral method development. Two of the most useful chiral stationary phases (CSPs), a cellulosic (Chiralcel OJ-R) and a Pirkle-type (Chirex 3005), were chosen as the chiral selectors in this study to systematically investigate the factors affecting chiral separation of a series of Fmoc-amino acids. The effects of temperature, pH, buffer concentration, buffer type and organic modifiers on retention and chiral selectivity were compared between the cellulosic and the Pirkle-type selectors. Temperature affected retention and selectivity, as predicted by thermodynamics, using both types of chiral selectors. On the cellulosic CSP, buffer pH was the only factor which caused a significant change in chiral selectivity, while several factors, including buffer concentration and organic modifier type, affected chiral selectivity on the Pirkle-type CSP. The results also indicated that the cellulosic CSP had a retention mechanism analogous to conventional reversed-phase LC, however, the Pirkle-type selector appeared to show a mixed mode retention mechanism for these analytes.

D- and L-dihydroxyphenylalanine (D- and L-DOPA) and enantiomers of the tetrahydroisoquinoline alkaloids salsolinol (SAL), 1-carboxysalsolinol (1-CSAL), and cis-3-carboxysalsolinol (3-CSAL) were chromatographed using sulfated beta-cyclodextrin (S-beta-CD) as a chiral selector in mobile phases with conventional reversed-phase ODS columns. S-beta-CD is a very effective chiral selector for SAL and 3-CSAL, less effective although still useful for resolving D- and L-DOPA, and gives only meager separation of the optical isomers of 1-CSAL. Stoichiometries of the complexes which form between S-beta-CD and SAL enantiomers are 1:1. Interactions between carboxylated substances and S-beta-CD appears to be more complex. Retention of the solutes studied is characterized by favorable negative enthalpy and unfavorable negative entropy changes. Enthalpy changes outweigh entropy values.

The RP HPLC method (LiChrosorb RP18 or Separon SGX C18 column, acetonitrile-water 86:14 v/v mobile phase) was applied for enantiomeric separation of topologically chiral 5-bromo-25,26-bis(diethoxyphosphoryl)calix[4]arene 9 or 25-ethyl-26-dihydroxyphosphoryl-calix[4]arene 5. Separation of calixarene 9 was achieved by the addition of D-(-)-tartaric acid which formed hydrogen bonded diastereomeric associates with 9 to the mobile phase. Calixarenephosphoric acid 5 was transformed into diastereomeric salt 6 by addition of L-(-)-alpha-phenylethylamine before RP HPLC separation.

With the dramatic recent growth in importance of asymmetric syntheses, new applications or approaches for analyses of enantiomeric excess (% e.e.) of samples continue to become more essential. Nuclear magnetic resonance (NMR) spectroscopy provides a wide range of powerful methods which are complementary to chromatographic or electrophoretic-based approaches. This present review focuses on representative and selective recent examples (through mid-1999) of English language reports on NMR methods for % e.e. determination.

[(1-->6)-2,5-Anhydro-3,4-di-O-ethyl-D-glucitol]-bound silica gel (CSP 4a), which was prepared by a two-step reaction, was used as a chiral stationary phase in high-performance liquid chromatography. The chiral recognition ability of the CSP 4a for racemates was examined using aq. NaClO4 (pH 2) and aq. NaClO4 (pH 2)/CH3CN as the eluents. For the resolution of amino acids and amino acid methyl esters, the D-isomers were eluted first. The separation factors of many of the racemates were 1.1-1.4, and the resolution factors were 0.59-7.75. This stationary phase showed a relatively high-resolving power toward compounds having a bulky substituent on the chiral carbon, such as phenylglycine and 1-(1-naphthyl)ethylamine.

(S)-Ethyl 2-methylbutanoate is an important aroma compound in apples and serves as an indicator for genuineness of apple products due to its high optical purity of greater than 98% enantiomeric excess [T. Koenig and P. Schreier, Zeitsch. Lebensm.-Unters. Forsch. A, 1999, 208, 130-133; K. Schumacher et al., J. Agric. Food Chem., 1998, 46, 4496-4500]. The origin of minor amounts of (R)-ethyl 2-methylbutanoate is unknown as naturally occurring (+)-isoleucine, the proposed precursor of (S)-ethyl 2-methylbutanoate is enantiomerically pure. Since ethyl (E)-2-methyl-2-butenoate (ethyl tiglate) was recently discovered as a natural apple constituent and hydrogenation activity in apples was demonstrated we proposed ethyl tiglate as a precursor of (R)-ethyl 2-methylbutanoate. D4-3,4,4,4-ethyl tiglate was synthesized and was injected into ripe apple fruits (cv. Golden Delicious, Red Delicious and Granny Smith). After 3, 6, and 12 days apple volatiles were isolated by solid phase extraction on XAD-2 and the metabolites formed from D4-3,4,4,4-ethyl tiglate were analyzed by capillary gas chromatography-mass spectrometry (GC-MS). Ethyl 2-methylbutanoate, 2-methylbutyl acetate, 2-methylbutanol, and 2-methylbutanoic acid were identified as major transformation products. Chiral evaluation of the metabolites by multidimensional GC-MS revealed enantiomeric excesses ranging from 43% (S) to 30% (R) depending on the apple cultivar, sampling date and metabolite. The data show for the first time that the natural apple constituent ethyl tiglate can serve as a source for (R)-2-methylbutanol derivatives.

Optical resolution of the title compound, TERNOL (1), having bis-bidentate sites of axial chiralities was succesful. A racemic mixture of 1 was converted to the tetracamphorsulfonate 2 in high yield, and a single recrystallization of 2 under kinetic conditions effectively separated the diastereomers. The crystal part obtained in 44% yield consisted of (S,S)-2 of 96% diastereomer excess (de), and the solution part (50% yield) contained (R,R)-2 of 96% de. An additional recrystallization of the each part resulted in diastereomerically pure 2 in high yield. Hydride reduction of the ketones in the camphorsulfonyl groups of 2 caused smooth intramolecular transesterification, and enantiomerically pure (R,R)-1 and (S,S)-1 were obtained in good yields.

Cationic Ag(I)-BINAP complex has been shown to be an effective catalyst for Mukaiyama aldol reaction between aldehyde and silyl enol ether derivatives. AgPF6-BINAP is very active in this reaction and can achieve high enantiomeric excess under mild conditions. Addition of a small amount of water enhanced the reactivity to suggest the contribution of enolate anion intermediate. AgOAc-BINAP, which in noncationic species, showed an extraordinary high activity although %ee was low.

omicron-Substituted diphenylmethanols were enantioresolved by the method of chiral dichlorophthalic acid amide, yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X-ray crystallography of chiral dichlorophthalate esters.