Carbocyclic 5′‐norcytidine (5′‐norcarbodine)

A preparation of (1′R,2′S,3′R,4′S)‐1‐(2′,3′,4′‐trihydroxycyclopent‐1′‐yl)‐lH‐cytosine (5′‐norcarbodine, 3 ) has formally been achieved in 2 steps from (+)‐(1R,4S)‐4‐hydroxy‐2‐cyclopenten‐1‐yl acetate ( 4 ) and cytosine. The L‐like enantiomer of 3 (that is, 6 ) is also reported using the enantiomer of 4 (that is, 7 ). In evalu ating 3 and 6 for antiviral potential against a number of viruses, compound 3 was found to have activity towards Epstein‐Barr virus (EBV).     

The chiral bioconversion and preclinical pharmacokinetic analysis of (R)‐(+)‐rabeprazole in beagle dogs by HPLC and HPLC‐MS/MS

In order to accurately investigate the preclinical pharmacokinetics of (R)‐(+)‐rabeprazole sodium injection, a reliable high‐performance liquid chromatography (HPLC) method was developed using a Chiral‐AGP column to prove that there is no chiral bioconversion of (R)‐(+)‐rabeprazole to (S)‐(?)‐rabeprazole in beagle dogs after single intravenous administration of (R)‐(+)‐rabeprazole sodium injection. An HPLC–tandem mass spectrometry (HPLC‐MS/MS) method for analysis of (R)‐(+)‐rabeprazole was developed and validated, and used to acquire the pharmacokinetic parameters in beagle dogs. (R)‐(+)‐Rabeprazole and internal standard omeprazole were extracted from plasma samples by protein precipitation and separated on a C₁₈ column using methanol–5 mm ammonium acetate as mobile phase. Detection was performed using a turbo‐spray ionization source and mass spectrometric positive multi‐reaction monitoring mode. The linear relationship was achieved in the range from 2.5 to 5000 ng/mL. The method also afforded satisfactory results in terms of sensitivity, specificity, precision, accuracy and recovery as well as the stability of the analyte under various conditions, and was successfully applied to a preclinical pharmacokinetic study in beagle dogs after single intravenous administrations of (R)‐(+)‐rabeprazole sodium injection at 0.33, 2 and 6 mg/kg. Copyright © 2013 John Wiley & Sons, Ltd.     

New palladium(II)–N‐heterocyclic carbene complexes containing benzimidazole‐2‐ylidene ligand derived from menthol: synthesis,characterization and catalytic activities

A new series of sterically hindered ligands containing (1R,2S,4R)‐(+)‐menthoxymethyl group attached to benzimidazole‐based N‐heterocyclic carbene (NHC), palladium–bis‐NHC complexes and (κ²‐C,N)‐palladacyclic NHC complexes have been synthesized and characterized using appropriate spectroscopic techniques. Catalytic performance of the palladium complexes has been investigated for allylic alkylation, Suzuki and Heck carbon–carbon coupling reactions. These complexes smoothly catalyse the carbon–carbon bond formation reactions. Copyright © 2016 John Wiley & Sons, Ltd.     

Coulomb Explosion Imaged Cryptochiral (R,R)‐2,3‐Dideuterooxirane: Unambiguous Access to the Absolute Configuration of (+)‐Glyceraldehyde

The absolute configuration of (R,R)‐2,3‐dideuterooxirane, which has been independently determined using Coulomb explosion imaging, has been unambiguously chemically correlated with the stereochemical key reference (+)‐glyceraldehyde. This puts the absolute configuration of D (+)‐glyceraldehyde on firm experimental grounds.     

The Absolute Configuration of (+)‐Ethyl cis‐1‐Benzyl‐3‐hydroxypiperidine‐4‐carboxylate and (+)‐4‐Ethyl 1‐Methyl cis‐3‐Hydroxypiperidine‐1,4‐dicarboxylate; a Revision

Discrepancies between chiroptical data from the literature and our determination of the structure of the title compounds (+)‐ 5 and (+)‐ 9a were resolved by an unambiguous assignment of their absolute configuration. Accordingly, the dextrorotatory cis‐3‐hydroxy esters have (3R,4R)‐ and the laevorotatory enantiomers (3S,4S)‐configuration. The final evidences were demonstrated on both enantiomers (+)‐ and (?)‐ 5 by biological reduction of 4 by bakers' yeast and stereoselective [Ru^II(binap)]‐catalyzed hydrogenations of 4 (Scheme 2), by the application of the NMR Mosher method on (+)‐ and (?)‐ 5 (Scheme 3), as well as by the transformation of (+)‐ 5 into a common derivative and chiroptical correlation (Scheme 4).     

Synthesis of Some Novel Amino Phenols with Octahydro‐1,1′‐binaphthyl Backbone

A series of new octahydro‐1,1′‐binaphthyl derivatives, namely (R)‐(+)‐2‐(N, N‐dialkylamino)‐2′‐hydroxy‐5,5′,6,6′,7, 7′,8,8′‐octahydro‐1,1′‐binaphthyls (7,9), have been synthesized. Their asymmetric induction for enantioselective addition of Et₂Zn to benzaldehyde was examined and it was found that (R)‐(+)‐2‐(N‐cyclohexyl‐N‐methylamino)‐2′‐hydroxy‐5, 5′,6,6′,7,7′,8,8′‐octahydro‐1,1′‐binaphthyl (9c) exhibited the best asymmetric induction among the ligands prepared, up to 55% ee of 1‐phenylpropanol being obtained.     

Water‐Promoted Kinetic Separation of trans‐ and cis‐Limonene Oxides

The efficient hydrolytic kinetic separation of trans/cis‐(R)‐(+)‐limonene oxides was realized in a 1:1 mixed solvent of water and 1,4‐dioxane without additional catalyst. Optically pure trans‐(R)‐(+)‐limonene oxide was recovered in high yield (77%).     

Mass‐Selected Circular Dichroism of Supersonic‐Beam‐Cooled [D4]‐(R)‐(+)‐3‐Methylcyclopentanone

UV spectroscopy and electronic circular dichroism (ECD) experiments on supersonic‐beam‐cooled deuterated (R)‐(+)‐3‐methylcyclopentanone ([D₄]‐(R)‐(+)‐3‐MCP) have been performed by using a laser mass spectrometer. The spectral resolution not only allowed excitation and CD measurements for single vibronic transitions but also for the rotational P, Q, and R branches of these transitions. The investigated transition showed the largest anisotropy factor ever observed for chiral molecules in the gas phase, which, due to residual saturation of the excited transition, represents only a lower limit for the real anisotropy factor. Furthermore, one‐color (1+1+1) and two‐color (1+1′) resonance‐enhanced multiphoton ionization (REMPI) measurements were performed and the effusive‐beam (room temperature) and supersonic‐beam results for [D₄]‐(R)‐(+)‐3‐MCP were compared. These results allowed a differentiation between single‐step ECD (comparable to conventional ECD) and cumulative ECD (only possible in multiphoton excitation) under supersonic‐beam conditions.     

Asymmetric Syntheses of New Polyhydroxylated Quinolizidines: Cross‐Aldol Reactions of 7‐Oxabicyclo[2.2.1]heptan‐2‐one and 3a,4a,7a,7b‐Tetrahydro[1,3]dioxolo[4,5]furo[2,3‐d]isoxazole‐3‐carbaldehyde Derivatives

The cross‐aldolization of (−)‐(1S,4R,5R,6R)‐6‐endo‐chloro‐5‐exo‐(phenylseleno)‐7‐oxabicyclo[2.2.1]heptan‐2‐one ((−)‐ 25 ) and of (+)‐(3aR,4aR,7aR,7bS)‐ ((+)‐ 26 ) and (−)‐(3aS,4aS,7aS,7bR)‐3a,4a,7a,7b‐tetrahydro‐6,6‐dimethyl[1,3]dioxolo[4,5]furo[2,3‐d]isoxazole‐3‐carbaldehyde ((−)‐ 26 ) was studied for the lithium enolate of (−)‐ 25 and for its trimethylsilyl ether (−)‐ 31 under Mukaiyama's conditions (Scheme 2). Protocols were found for highly diastereoselective condensation giving the four possible aldols (+)‐ 27 (`anti'), (+)‐ 28 (`syn'), 29 (`anti'), and (−)‐ 30 (`syn') resulting from the exclusive exo‐face reaction of the bicyclic lithium enolate of (−)‐ 25 and bicyclic silyl ether (−)‐ 31 . Steric factors can explain the selectivities observed. Aldols (+)‐ 27 , (+)‐ 28 , 29 , and (−)‐ 30 were converted stereoselectively to (+)‐1,4‐anhydro‐3‐{(S)‐[(tert‐butyl)dimethylsilyloxy][(3aR,4aR,7aR,7bS)‐3a,4a,7a,7b‐tetrahydro‐6,6‐dimethyl[1,3]dioxolo[4,5]‐furo[2,3‐d]isoxazol‐3‐yl]methyl}‐3‐deoxy‐2,6‐di‐O‐(methoxymethyl)‐α‐D ‐galactopyranose ((+)‐ 62 ), its epimer at the exocyclic position (+)‐ 70 , (−)‐1,4‐anhydro‐3‐{(S)‐[(tert‐butyl)dimethylsilyloxy][(3aS,4aS,7aS,7bR)‐3a,4a,7a,7b‐tetrahydro‐6,6‐dimethyl[1,3]dioxolo[4,5]furo[2,3‐d]isoxazol‐3‐yl]methyl}‐3‐deoxy‐2,6‐di‐O‐(methoxymethyl)‐α‐D ‐galactopyranose ((−)‐ 77 ), and its epimer at the exocyclic position (+)‐ 84 , respectively (Schemes 3 and 5). Compounds (+)‐ 62 , (−)‐ 77 , and (+)‐ 84 were transformed to (1R,2R,3S,7R,8S,9S,9aS)‐1,3,4,6,7,8,9,9a‐octahydro‐8‐[(1R,2R)‐1,2,3‐trihydroxypropyl]‐2H‐quinolizine‐1,2,3,7,9‐pentol ( 21 ), its (1S,2S,3R,7R,8S,9S,9aR) stereoisomer (−)‐ 22 , and to its (1S,2S,3R,7R,8S,9R,9aR) stereoisomer (+)‐ 23 , respectively (Schemes 6 and 7). The polyhydroxylated quinolizidines (−)‐ 22 and (+)‐ 23 adopt `trans‐azadecalin' structures with chair/chair conformations in which H−C(9a) occupies an axial position anti‐periplanar to the amine lone electron pair. Quinolizidines 21 , (−)‐ 22 , and (+)‐ 23 were tested for their inhibitory activities toward 25 commercially available glycohydrolases. Compound 21 is a weak inhibitor of β‐galactosidase from jack bean, of amyloglucosidase from Aspergillus niger, and of β‐glucosidase from Caldocellum saccharolyticum. Stereoisomers (−)‐ 22 and (+)‐ 23 are weak but more selective inhibitors of β‐galactosidase from jack bean.     

Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

Nucleophilic ring‐opening reactions of 3‐aryl‐1‐benzylaziridine‐2‐carboxylates were examined by using O‐nucleophiles and aromatic C‐nucleophiles. The stereospecificity was found to depend on substrates and conditions used. Configuration inversion at C(3) was observed with O‐nucleophiles as a major reaction path in the ring‐opening reactions of aziridines carrying an electron‐poor aromatic moiety, whereas mixtures containing preferentially the syn‐diastereoisomer were generally obtained when electron‐rich aziridines were used (Tables 1–3). In the reactions of electron‐rich aziridines with C‐nucleophiles, S_N2 reactions yielding anti‐type products were observed (Table 4). Reductive ring‐opening reaction by catalytic hydrogenation of (+)‐trans‐(2S,3R)‐3‐(1,3‐benzodioxol‐5‐yl)aziridine‐2‐carboxylate (+)‐trans‐ 3c afforded the corresponding α‐amino acid derivative, which was smoothly transformed into (+)‐tert‐butyl [(1R)‐2‐(1,3‐benzodioxol‐5‐yl)‐1‐methylethyl]carbamate((+)‐ 14 ) with high retention of optical purity (Scheme 6).     

Stereoselective Synthesis of (−)‐(1R,1′R,5′R,7′R)‐1‐Hydroxy‐exo‐brevicomin and (+)‐exo‐Brevicomin from 3,4,6‐Tri‐O‐acetyl‐D‐glucal

Stereoselective syntheses of (?)‐(1R,1′R,5′R,7′R)‐1‐hydroxy‐exo‐brevicomin ( 1 ) and (+)‐exo‐brevicomin ( 2 ) were accomplished from 3,4,6‐tri‐O‐acetyl‐D ‐glucal ( 5 ; Schemes 2 and 3). Chemoselective reduction, Grignard reaction, Barton? McCombie deoxygenation, and ketalization were used as key steps.     

(+)‐(R,Z)‐5‐Muscenone and (−)‐(R)‐Muscone by Enantioselective Aldol Reaction and Grob Fragmentation

(+)‐(R,Z)‐5‐Muscenone ((R)‐ 1 ) was synthesized by an enantioselective aldol reaction, catalyzed by new ephedrine‐type Ti reagents (up to 70 % enantiomeric excess). Substrate‐directed diastereoselective reduction of the aldol product and Grob fragmentation of the tosylate of the resultant 1,3‐diol afforded (+)‐ 1 . This approach also gave access to (?)‐(R,E)‐5‐muscenone and (?)‐(R)‐muscone.     

Application of off‐line two‐dimensional high‐performance countercurrent chromatography on the chloroform‐soluble extract of Cuscuta auralis seeds

In this study, the chloroform‐soluble extract of Cuscuta auralis was separated successfully using off‐line two‐dimensional high‐performance countercurrent chromatography, yielding a γ‐pyrone, two alkaloids, a flavonoid, and four lignans. The first‐dimensional countercurrent separation using a methylene chloride/methanol/water (11:6:5, v/v/v) system yielded three subfractions (fractions I–III). The second‐dimensional countercurrent separations, conducted on fractions I–III using n‐hexane/ethyl acetate/methanol/water/acetic acid (5:5:5:5:0, 3:7:3:7:0, and 1:9:1:9:0.01, v/v/v/v/v) systems, gave maltol ( 1 ), (−)‐(13S)‐cuscutamine ( 2 ), (+)‐(13R)‐cuscutamine ( 3 ), (+)‐pinoresinol ( 4 ), (+)‐epipinoresinol ( 5 ), kaempferol ( 6 ), piperitol ( 7 ), and (9R)‐hydroxy‐d ‐sesamin ( 8 ). To the best of our knowledge, maltol was identified for the first time in Cuscuta species. Furthermore, this report details the first full assignment of spectroscopic data of two cuscutamine epimers, (−)‐(13S)‐cuscutamine and (+)‐(13R)‐cuscutamine.     

Kinetic Resolution of the Racemic 2‐Hydroxyalkanoates Using the Enantioselective Mixed‐Anhydride Method with Pivalic Anhydride and a Chiral Acyl‐Transfer Catalyst

A variety of optically active 2‐hydroxyalkanoates and the corresponding 2‐acyloxyalkanoates are produced by the kinetic resolution of racemic 2‐hydroxyalkanoates by using achiral 2,2‐diarylacetic acid with hindered carboxylic anhydrides as the coupling reagents. The combined use of diphenylacetic acid, pivalic anhydride, and (+)‐(R)‐benzotetramisole ((R)‐BTM) effectively produces (S)‐2‐hydroxyalkanoates and (R)‐2‐acyloxyalkanoates from the racemic 2‐hydroxyalkanoates (s‐values=47–202). This protocol directly provides the desired chiral 2‐hydroxyalkanoate derivatives from achiral diarylacetic acid and racemic secondary alcohols that do not include the sec‐phenethyl alcohol moiety by using the transacylation process to generate the mixed anhydrides from the acid components with bulky carboxylic anhydrides under the influence of the chiral acyl‐transfer catalyst. The transition state that provides the desired (R)‐2‐acyloxyalkanoate from (R)‐2‐hydroxyalkanoate included in the racemic mixture is disclosed by DFT calculations, and the structural features of the transition form are also discussed.     

A Practical and Enantiospecific Synthesis of (−)‐(R)‐ and (+)‐(S)‐Piperidin‐3‐ols

A highly enantiospecific, azide‐free synthesis of (?)‐(R)‐ and (+)‐(S)‐piperidin‐3‐ol in excellent yield was developed. The key step of the synthesis involves the enantiospecific ring openings of enantiomerically pure (R)‐ and (S)‐2‐(oxiran‐2‐ylmethyl)‐1H‐isoindole‐1,3(2H)‐diones with the diethyl malonate anion and subsequent decarboxylation.     

Synthesis,Characterization, and Application of Platinum(II) Complexes Incorporating Racemic and Optically Active 4‐Chloro‐5‐Methyl‐1‐Phenyl‐1,2,3,6‐Tetrahydrophosphinine Ligand

An efficient resolution method was elaborated for the preparation of (+)‐4‐chloro‐5‐methyl‐1‐phenyl‐1,2,3,6‐tetrahydrophosphinine oxide using the acidic Ca²⁺ salt of (–)‐O,O‐di‐p‐toluoyl‐(2R,3R)‐tartaric acid. Crystal structure of the diastereomeric complex was evaluated by single crystal X‐ray analysis. Beside this, the absolute P‐configuration was also determined by a circular dichroism (CD) spectroscopic study including theoretical calculations. The tetrahydrophosphinine oxide was then converted to the corresponding platinum complex whose stereostructure was investigated by high‐level quantum chemical calculations. The Pt complex was tested as a catalyst in the hydroformylation of styrene.     

Asymmetric hydrogenation of ketones catalyzed by silica‐supported chitosan‐iron‐nickel complex

A new silica‐supported biopolymer‐metal complex, silica‐supported chitosan‐iron‐nickel complex was prepared by a very simple method. This complex catalyst can be used as a catalyst in the asymmetric hydrogenation of propiophenone to (R)‐(+)‐1‐phenyl‐1‐propanol and acetophenone to (R)‐(+)‐1‐phenyl ethanol in 91.7 and 77.7% optical yields, respectively, at 110°C and under 70 kg/cm² pressure. The catalyst could be reused several times without any remarkable change in the catalytic activity. Copyright © 2004 John Wiley & Sons, Ltd.     

Asymmetric hydration of alkenes catalyzed by wool‐palladium complex

A wool‐palladium complex has been found to be able to catalyze the asymmetric hydration of 1‐octene to (S)‐(+)‐2‐octanol and 1‐decene to (R)‐(+)‐2‐decanol under 1 atm N₂ and at 70°C. The optical yields were greatly affected by Pd content in wool‐palladium complex, reaction time and so on, when the proper conditions were selected, (S)‐(+)‐2‐octanol and (R)‐(+)‐2‐decanol could be obtained in 83.2 and 75.6%e.e. optical yield respectively. This chiral natural biopolymer‐palladium complex catalyst was very easy to prepare and could be reused several times without appreciable change in catalytic activity. Copyright © 2004 John Wiley & Sons, Ltd.     

Highly Enantioselective Formation of α‐Allyl‐α‐Arylcyclopentanones via Pd‐Catalysed Decarboxylative Asymmetric Allylic Alkylation

A highly enantioselective Pd‐catalysed decarboxylative asymmetric allylic alkylation of cyclopentanone derived α‐aryl‐β‐keto esters employing the (R,R)‐ANDEN‐phenyl Trost ligand has been developed. The product (S)‐α‐allyl‐α‐arylcyclopentanones were obtained in excellent yields and enantioselectivities (up to >99.9 % ee). This represents one of the most highly enantioselective formations of an all‐carbon quaternary stereogenic center reported to date. This reaction was demonstrated on a 4.0 mmol scale without any deterioration of enantioselectivity and was exploited as the key enantioselective transformation in an asymmetric formal synthesis of the natural product (+)‐tanikolide.     

(2E)‐N‐(2‐Iodo‐4,6‐dimethylphenyl)‐2‐methylbut‐2‐enamide

The title compound, C₁₄H₁₈INO, crystallizes as +sc/+sp/+sc 2‐iodoanilide molecules (and racemic opposites) and shows significant intermolecular I...O interactions in the solid state, forming dimeric pairs about centres of symmetry. Under asymmetric Heck conditions, the S enantiomer of the dihydroindol‐2‐one was obtained using (R)‐(+)‐2,2′‐bis(diphenylphosphino)‐1,1′‐binaphthyl [(R)‐BINAP], suggesting a mechanism that proceeds by oxidative addition to give the title (P) enantiomer of the compound and pro‐S coordination of the Re face of the alkene in a conformation similar to that defined crystallographically, except that rotation about the C—C bond of the butenyl group is required.