Operationally Simple Enantioselective Silane Reduction of Ketones by the [Ir(OMe)(cod)]2/Azolium Catalytic System

An operationally simple protocol was designed for the enantioselective silane reduction (ESR) of ketones using air- and moisture-stable [Ir(OMe)(cod)]2 (cod = 1,5-cyclooctadiene) (3) as a metal catalyst precursor. This reaction was driven by chiral hydroxyamide-functionalized azolium salt 2. The catalytic ESR reaction could be performed under benchtop conditions at room temperature. Treatment of 2 with 3 in THF yielded the monodentate IrCl(NHC)(cod) (NHC = N-heterocyclic carbene) complex 4 in 93% yield, herein the anionic methoxy ligand of 3 serves as an internal base that deprotonates the azolium ring of 2. The well-defined Ir complex 4 catalyzed the ESR reaction of propiophenone (6) with (EtO)2MeSiH using the pre-mixing reaction procedure. Based on this success, the catalytic ESR reaction was designed and implemented using an in situ-generated NHC/Ir catalyst derived from 2 and 3. Thus, a wide variety of aryl ketones could be reduced to the corresponding optically active alcohols in moderate to excellent stereoselectivities at room temperature without temperature control. Since the high catalytic activity of 3 was observed, we next evaluated several other transition metal catalyst precursors for the catalytic ESR reaction under the influence of 2. This evaluation revealed that Ir(acac)(cod) (acac = acetylacetonate) (28) and [IrCl(cod)]2 (5) can be successfully used as metal catalyst precursors in the ESR reaction.

Enantioselective analytical methods in chiral drug metabolism

The chiral nature of biological systems enables their stereoselective interaction with chiral compounds. It has been well documented that the enantiomers ofa chiral drug may show differences in drug disposition especially in metabolic behavior. As a result, it is of vital importance to separate the enantiomers of a chiral drug in metabolic studies. This paper discusses enantioselective methods （include high-performance liquid chromatography, gas chromatography, capillary electrophoresis and high-performance liquid chromatography-mass spectrometry） that applied in chiral drug metabolism, using most recent examples where possible.

Enantioselective separation and zebrafish embryo toxicity of insecticide beta-cypermethrin

Enantioselectivity of chiral pollutants is receiving growing concern due to the difference in toxicology and environment fate between enantiomers.In this study,enantiomers of insecticide beta-cypermethrin （beta-CP） were separated on selected chiral column by HPLC,and the toxicity of enantiomers was evaluated using the zebrafish embryo-larval assays.The enantiomers of beta-CP were baseline separated on Chiralcel OD and Chiralpak AD columns and detected by circular dichroism （CD） at 236 nm.Better separation could be achieved at lower temperature （e.g.,20°C） and with lower levels of polar modifiers.Pure enantiomers were obtained on Chiralcel OD.The CD spectra of enantiomers were recorded.By comparing the elution order with a previous similar study,the absolute configuration of beta-CP enantiomers was determined.The individual enantiomers were used in zebrafish embryo test,and the results showed that beta-CP enantioselectively induced yolk sac edema,pericardial edema and crooked body.The 1R-cis-αS and 1R-trans-αS enantiomers showed strong developmental toxicities at concentration of 0.1 mg/L,while the 1S-cis-αR and 1S-trans-αR induced no malformations at higher concentration （e.g.,0.3 mg/L）.The results suggest that the enantioselective toxicological effects of beta-CP should be considered when evaluating its ecotoxicological effects.

Lipase immobilized on HOOC-MCF:A highly enantioselective catalyst for transesterification resolution of (R,S)-1-phenylethanol

Pseudomonas cepacia lipase （PSL） immobilized on the carboxyl-functionalized meso-cellular foams （HOOC-MCF） was used for the transesterification resolution of （R,S）-l-phenylethanol in organic solvent. The results showed that the ee value of （S）-1- phenylethanol and （R）-1-phenylethyl acetate reached 99% with 50% conversion of 1-phenylethanol using toluene as solvent. Furthermore, it was found that PSL/HOOC-MCF exhibited high enantioselectivity in organic solvent with log P ≤ 2 such as toluene and hexane.

Baker's yeast mediated reduction of substituted acenaphthenequinones: Regio-and enantioselective preparation of mono-hydroxyacenaphthenones

Baker's yeast mediated reduction of acenaphthenequinone within 4-10 h afforded mono-hydroxyacenaphthenone mainly with low enantioselectivity, the substrate and mono-hydroxyacenaphthenone product almost converted to dihydroxyacenaphthene after 48 h. By control of the reaction time and in the presence of DMF as co-solvent, the reduction of 6-substituted acenaphthenequinones under vigorous agitation afforded the corresponding 2-hydroxyacenaphthenones in 24-84% yields with 10-93% ee.

Comparison of reversed-phase enantioselective HPLC methods for determining the enantiomeric purity of (S)-omeprazole in the presence of its related substances

A simple analytical high-performance liquid chromatography （HPLC） method was applied for the en- antiomeric excess determination of esomeprazole （（S）-OME）, the enantiopure active ingredient con- tained in drug products, in the presence of its potential organic impurities A-E. The enantioselective separation was accomplished on the immobilized-type Chiralpak ID-3 chiral stationary phase （CSP） under reversed-phase conditions. The results were evaluated and compared with those obtained by the official enantioselective method of European Pharmacopoeia used as the reference for checking the enantiomeric excess of （S）-OME. It has been established that the use of the Chiralpak ID-3 CSP allows the determination of the enantiomeric purity of （S）-OME without any interference coming from its chiral and achiral related substances. The analytical procedure of the drug regulatory agencies based on the AGP CSP suffered instead from poor specificity due to overlap of the peaks pertinent to the achiral impurity A and the chiral impurity （R）-OME （impurity F）.

Resolution of 2-Octanol via Lipase-catalyzed Enantioselective Acetylation in Organic Solvents

The lipases from different sources were screened for their ability to catalyze the resolution of 2-octanol in organic solvents with vinyl acetate as the acylating reagent. The medium effect has been studied on the irreversible transesterification with varying water activity(a_w). The influence of vinyl acetate concentration on it has also been investigated. Under the optimal conditions, the enantiomeric ratio(E value) of pseudomonas fluorescence lipase(PFL) exceeded 200 with an enantiomeric excess(e.e.) of S-2-octanol above 99% at a 51% degree of conversion.

Ultrasound-promoted Lipase-catalyzed Enantioselective Transesterification of (R,S)-Glycidol

Enantioselective transesterification of glycidol with vinyl butyrate as an acyl donor was investigated in the presence of Bacillus subtilis lipase（BSL2） as catalyst. Comparison studies demonstrate the advantage of ultrasound over the conventional shaking for the enzymatic reaction in non-aqueous media. The effects of reaction conditions（ultrasound power, temperature, water activity and pH） on the activity and enantioselectivity were also investigated. Under the optimum conditions, the synthetic activity of BSL2 was 2.95 μmol？min？1？mg？1 and the enantioselectivity（E value） was 52.2. Compared with conventional shaking, ultrasound made the synthetic activity and the enantioselectivity increase 9.5-fold and 1.4-fold, respectively. Furthermore, the repeated use of BSL2 for five cycles resulted in no obvious loss of enzyme activity, suggesting that the enzyme is stable under low power ultrasound conditions.

First Enantioselective Synthesis of Daphneticin

An enantioselective total synthesis of chiral daphneticin is reported firstly.

Novel chiral thioureas for highly enantioselective Michael reactions of malonates to nitroalkenes

Highly efficient Michael addition reactions of malonates to nitroalkenes catalyzed by novel chiral thioureas derived from optically pure BINOL and amino acids are reported. Various trans-nitroalkenes reacted with malonates affording the desired products in up to 95% yield with excellent enantioselectivities （up to 97% ee）.

Enantioselective reduction of acetophenone analogues using carrot and celeriac enzymes system

The enantioselective reduction of acetophenone analogues catalyzed by carrot and celeriac was performed in moderate conversions and excellent enantiomeric excesses.The steric factors and electronic effects of the substituents at the aromatic ring were found to significantly affect the efficiency of the enantioselective reduction of acetophenone analogues,while they had a little effect on the enantioselectivity of acetophenone analogues reduction.It was also found that the conversions of acetophenone analogu...

Enantioselective hydrogenation of acetophenone by(1S,2S)-DPEN-Ru(Ⅱ)Cl_2(PPh_3)_2 encapsulated in Al-MCM-41

A chiral ruthenium complex[（1S,2S）-DPEN]-RuCl_2（PPh_3）_2（DPEN = 1,2-diphenylethylenediamine,PPh_3 = triphenylphosphine） was encapsulated in the channel of Al-MCM-41 by electrostatic adsorption and 1,1-dichlorosilacyclobutane modification.The prepared heterogeneous catalyst showed the same catalytic activity and enantioselectivity as the corresponding homogeneous catalyst in the asymmetric hydrogenation of acetophenone,and could be reused at least seven times without significant loss of catalytic activity and enantioselectivity.

MODIFICATION OF TRANSITION METAL CATIONS TO POLYMER-STABILIZED PLATINUM COLLOIDAL CLUSTERS IN ENANTIOSELECTIVE HYDROGENATION OF METHYL PYRUVATE

Modification of transition metal cations to polymer-stabilized Pt colloidal clusters modified with cinchonidine was studied in enantioselective hydrogenation of methyl pyruvate.Compared to the enantiomeric excess(e.e.)value(71.4%) obtained without the presence of metal cations,obvious e.e.enhancement(up to 82.5%)was resulted from the addition of Zn^(2+) but with a certain decrease in activity.The reaction parameters in the presence of Zn^(2+) were also studied.It was found that the Pt colloidal catalysts in the presence of metal cations performed very differently from that in the absence of metal cations.

A Simple and Highly Efficient Enantioselective Synthesis of (<i>S</i>)-Rivastigmine

A highly efficient and convenient procedure for the enantioselective synthesis of (S)-Rivastigmine, a cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson’s disease, is accomplished by the treatment of versatile, readily accessible (S)-(-)-2-methyl-2-propanesulfinamide with 3-hydroxyacetophenone. This protocol provides high yield and excellent enantiomeric excess in short step synthesis.

Enantioselective assay of S(+)- and R(-)-propafenone in human urine by using RP-HPLC with pre-column chiral derivatization

The enantioselective assay for S(+)- and R(-)-propafenone (PPF) in human urine that developed in this work involves extraction of propafenone from human urine and using S(+)-propafenone as internal standard, chiral derivatization with 2,3,4,6-tetra-O-b-D-glucopranosyl isothiocyanate, and quantitation by an RP-HPLC system with UV detection (l=220 nm). A baseline separation of propafenone enantiomers was achieved on a 5-mm reverse phase ODS column, with a mixture of methanol:water:glacial acetic acid (25:12:0.02,v/v) as mobile phase. There was good linear relationship from 24.9 ng/ml to 1875.0 ng/ml for both of enantiomers. The regression equations of the standard curves based on CS-PPF (or CR-PPF ) versus ratio of AS-PPF/AS (or AR-PPF/AS ) were y=0.0032x-0.081, (r=0.999) for S-PPF and y=0.0033x+0.0039, (r=0.998) for R-PPF, respectively. The method抯 limit of detection was 12.5 ng/ml for both enantiomers, and the method抯 limit of quantitation was 28.20.52 ng/ml for S-PPF, 30.40.53 ng/ml for R-PPF (RSD<8%, n=5). The analytical method yielded average recovery of 98.9% and 100.4% for S-PPF and R-PPF, respectively. The relative standard deviation was no more than 6.11% and 6.22% for S-PPF and R-PPF, respectively. The method enabled study of metabolism of S(+)- and R(-)-propafenone in human urine. The results from 7 volunteers administered 150 mg racemic propafenone indicated that propafenone enantiomers undergo stereoselective metabolism and that in the human body, S(+)-propafenone is metabolized more extensively than R(-)- propafenone.

Enantioselective Hydrogenation of Ethyl 2-Oxo-4-phenylbutyrate on Cinchona-Platinum Catalysts

Enantioselective hydrogenation of ethyl 2-oxo-4-phenylbutyrate to ethyl （R）-2-hydroxy-4-phenyl- bu- tyrate on Pt/γ-Al2O3 modified by 10,11-dihydrocinchonidine was studied by investigating the influences of the amount of modifier, initial concentration of reactant, pressure and temperature on conversion and enantiometric excess in a stirred autoclave and the effects of the liquid velocity, gas velocity, modifier concentration and various catalytic beds in a trickle-bed reactor. The maximum optical yields were about 50% and 60% in the two types of reactors, respectively. It was assumed that the total hydrogenation rate included the reaction rates over the unmodified and modified active sites on platinum surface and a kinetic model, which fitted the experimental data well in autoclave, was obtained. A simplified plug-flow model was proposed to describe the bed average efficiency of trickle-bed reactor.

First Enantioselective Synthesis of (2R,3R)-and(2S,3S)-2-(4-hydroxyphenyl)-3-hydroxymethyl-1,4-benzodioxan-6-carbaldehyde

A novel enantioselective synthetic approach to 1,4-benzodioxane lignans was reported in which (2R, 3R)- and (2S, 3S)-2-(4-hydroxyphenyl)-3-hydroxymethyl-1, 4-benzodioxan-6-carbaldehyde were first synthesized.

First Enantioselective Synthesis of Isoamericanol A and Isoamericanin A

The first enantioselective synthesis approach to two chiral 1,4-benzodioxane neolignans isoamericanol A and isoamericanin A was reported.

Enantioselective Synthesis of (+)-Nuciferal, (+)-(E)-Nuciferol and (+)-α-Curcumene by Chiral Hydrogenesterification Reaction

Using chiral hydrogenesterification reaction as the key step, the stereoselective synthesisof (+)-nuciferal 1, (+)-(E)-nuciferol 2 and (+)-α-curcumene 3 has been achieved.