New Asymmetric Synthesis of Alkannin and Shikonin

A new approach for asymmetric synthesis of alkannin and shikonin is presented. The chiral centers of the targets were introduced via an asymmetric C-arylation of protected chiral glyceraldehyde in high de. The two enantiomers were prepared with the D-isopropylidenegly- ceraldehyde as the starting material.

Asymmetric Synthesis and Crystal Structure of a Bioactive Morpholine Derivative

A novel morpholine derivative was synthesized by Michael addition/internal nucleophilic substitution of 4-（L）-menthyloxy（1R,2S,5R）-butenolide with phenyl-glyalcohol under mild condition, and its structure was determined by X-ray diffraction. The target compound belongs to orthorhombic, space group P212121 with a = 5.7729（7）, b = 11.5032（14）, c = 25.161（3）A, Mr = 319.35, Z = 4, V = 1670.8（4）A^3, Dc = 1.270 g/cm3, μ（MoKα） = 0.094 mm^-1, F（000） = 680, Flack = 0.01（2）, R = 0.0398 and wR = 0.0914.

Asymmetric Synthesis of α-Substituted-γ-butyrolactone Empolying Prolinol Type of Auxiliaries

Eleven (S)-(-)-bishydrocarbyl-(1-alkanoylpyrrolidin-2-yl)-methanol derivatives of three types were synthesized from L-proline, asymmtrically selective alkylation products were obtained by LDA treatment and alkylation using methyl 2-bromoethyl ether, and three types of chiral α-substituted-γ-butyrolactones were obtained by hydrolyzing the alkylation products, with %e.e. being up to 89 percent.

A CONVENIENT ASYMMETRIC SYNTHESIS OF 1-AMINOALKYLPHOSPHONIC ACIDS^+

A convenient method for the asymmetric synthesis of 1-amino- alkylphosphonic acids was described.It involved the diastereoselctive alkylation of bicyclic chloromethylphosphonamide derived from(S)-2-ani- linomethylpyrrolidine followed by subsequent conversions leading to amino compounds by Staudinger method.Acid hydrolysis afforded the target molecule in good yield.

ASYMMETRIC SYNTHESIS Ⅻ:HIGHLY ENANTIOSELECTIVE SYNTHESIS OF α-AMINO ACIDS BY ALKYLATION OF THE KETIMINE FROM 2-HYDROXY-PINAN-3-ONE AND MENTHYL GLYCIN-ATE A DOUBLE ASYMMETRIC INDUCTION SYSTEM

A series of α-amino acids are obtained in 72-96% optical yields by alkylation of the ketimine derived from(+)-2-hydroxy-pinan-3-one and(-)-menthyl glycinate fol- lowed by hydrolysis of the alkylated intermediates with mineral acid.The double asymmetric induction are explained by the transition model of lithium enolate.

Asymmetric Synthesis of (-)-(4R, 5R)-4-[5-(Benzo[1, 3]dioxol-5-yl)-4- hydroxyl-1-(pyridin-2-yl)-4, 5-dihydro-1H-pyrazol-3-yl]benzamide

The asymmetric synthesis of （-）-（4R, 5R）-4-[5-（benzo[1, 3]dioxol-5-yl）-4-hydroxyl-1- （pyridin-2-yl）-4,5-dihydro-lH-pyrazol-3-yl]-benzamide with improved Juliá-Colonna asymmetric epoxidation procedure as key step was described.

Asymmetric Synthesis of (R)-and (S)-Moprolol

A simple and effective procedure for the enantioselective synthesis of （R）- and （S）-moprolol was described. The key step was the asymmetric synthesis of enantiopure （R）- and （S）-guaifenesin, which were synthesized from enantioenriched （R）-3-chloro-l,2-propanediol and （S）-epichlorohydrin via kinetics of hydrolysis resolution of racemic epichlorohydrin by chiral Salen-Co^Ⅲ complex. The e.e. values of both the optical compounds were above 98%, and the chemical structures of the target compounds were confirmed by ^1H NMR, ^13C NMR, IR, and MS.

Asymmetric Synthesis of Polyhydroxy Pyrrolidinonyl Nucleoside Analogues from Tartaric acid

Asymmetric synthesis of novel optically active nucleoside analogues 7 from natural tartaric acid is described. In the given nucleoside analogues an optically active polyhydroxy pyrrolidinonyl ring is in place of the tetrahydrofuran ring.

A New Asymmetric Synthesis of (+)-(3R, 4S, 5R, 7S)-Neoclausenamide via Intramolecular Nucleophilic Attack of Carbon Anion onto Cyclic Sulfate

An intramolecular nucleophilic substitution of carbon anion to cyclic sulfate was first employed in asymmetric synthesis of (+)-(3R, 4S, 5R, 7S)-neoclausenamide 1 which is a novel hepatoprotective lactam isolated from the dry leaves of Chinese folk medicine Clausena lansium (Lour) Skeel. The regioselectivity of beta-attack to this cyclic sulfate, just like its epoxide counterpart was attributed to the increased reactivity of beta-position by the phenyl group.

SYNTHESIS OF CHIRAL MIXED-LICAND COMPLEXES AND THEIR USE IN ASYMMETRIC SYNTHESIS OF CHRYSANTHEMIC ACID

Several chiral mixed-ligand complexes have been synthesized and their efficiency as catalysts for the asymmetric synthesis of chrysanthemic acid tested.

THE ASYMMETRIC SYNTHESIS OF AMINO ACIDS UNDER POLYMER-SUPPORTED PHASE TRANSFER CATALYTIC CONDITION

The optical alpha-amino acids were synthesized under room temperature by alkylation of N-(diphenyl methylene) glycine t-butyl ester under polymer-supported phase transfer conditions using polymer-supported cinchonine (or quinine) alkaloids as chiral phase transfer catalysts and dichloromethane as solvent, followed by hydrolysis of the above intermediates introduced to the final products-optical alpha-amino acids. This is a new method for the asymmetric synthesis of alpha-amino acids. The influences of catalyst, temperature, substrates, and organic solvents on the chemical yield and optical purities of products were studied.

Remote stereocontrol in the(4+2)cycloadditions of 1,7-zwitterions:Asymmetric synthesis of multifunctionalized tetrahydroquinoline derivatives

The scope of stereochemistry recognition usually occurs near the chiral scaffold of a ligand or catalyst.Remote stereocontrol,which can surpass the limits of stereorecognition of remote prochiral centers,has long been a challenging object of great interest in asymmetric catalysis.The current work realized the remote stereocontrol of 1,7-zwitterion intermediates formed from Huang's o-amino aryl MBH carbonates.With simple and easily accessibleβ-ICD as the bifunctional catalyst,multifunctionalized tetrahydroquinoline derivatives could be synthesized via(4+2)cycloadditions with excellent enantioselectivity and diastereoselectivity under mild conditions.The strategy possesses broad substrate scope,and three types of electron-deficient enones are successfully applied.Mechanistic studies disclosed the Lewis base-catalyzed reaction pathway,and H-bonding between the catalyst and enones is crucial for long-range stereocontrol.Scale-up reaction and transformations of the tetrahydroquinoline products demonstrated the potential of this strategy.

Asymmetric Synthesis of Anti-tuberculosis-specific Drug TBAJ-876 through Synergistic Li/Li Catalysis

TBAJ-876, developed by TB Alliance, a novel anti-tuberculosis-specific drug, has entered Phase II clinical trials. Herein, the first asymmetric synthesis of TBAJ-876 has been realized using synergistic Li/Li catalysis with excellent yield of 95% and 88 : 12 er (99.6 : 0.4 er, 10 : 1 dr after simple recrystallization). Furthermore, DFT calculations and 7Li-NMR analysis illustrated the mechanism of the synergistic reaction: a chiral Li-complex activates the nucleophile to control the stereoselectivity, while the other achiral Li-complex activates the electrophile to catalyze the carbonyl addition reaction. Additionally, this protocol has been successfully carried out at 5 gram-scale, showing its industrial potential.

Absolute asymmetric synthesis driven by circularly polarized light

Circularly polarized light(CPL)is an inherently chiral entity and is regarded as one of the possible deterministic signals that led to the evolution of homochirality in earth.Thus,CPL as an external physical field has been widely used in a technique known as absolute asymmetric synthesis,because a product enriched in one enantiomer is formed from racemic precursor molecules without the intervention of a chiral catalyst.In this review,we retrospect the historical research of CPL-induced absolute asymmetric synthesis,including chiral organic molecules,helical polymers,supramolecular assemblies,noble metal nanostructures.However,based on these results,we concluded that the chiral photon-matter interaction is very faint due to the arrangement of molecular bonds giving rise to chiral features,is over a smaller distance than the helical pitch of CPL,leading extremely small enantiomeric excess for product.Therefore,we highlight the recently emerged technology called superchiral field,in which the superchiral far-field and near-field could enhance the dissymmetry of optical field and near-field,respectively.In sum,we hope this review could bring some enlightenment to researchers and further improve the enantioselectivity of CPL-induced absolute asymmetric synthesis.

Asymmetric synthesis of syn-aryl-(2S,3R)-2-chloro-3-hydroxy esters via an engineered ketoreductase-catalyzed dynamic reductive kinetic resolution

We report here a generic,green synthesis of 17 valuable syn-aryl-(2S,3R)-2–chloro-3–hydroxy esters(syn-(2S,3R)-1)in 73%-99%isolated yields along with 6.1:1–83:1 dr and 31%~>99%ee,through dynamic reductive kinetic resolution of racemic arylα–chloroβ-keto esters(2)catalyzed by an engineered ketoreductase which was obtained via ep PCR-based directed evolution.The hectogram scale synthesis of syn-(2S,3R)-1b at a substrate concentration of 120 g/L showcased the application potential of the biocatalytic method developed presently.

Catalytic asymmetric synthesis of 1,4-enynes

1,4-Enyne units are ubiquitous skeletons in biologically active molecules and natural products.Especially,they represent versatile building blocks for abundant downstream derivatizations via controllable modifications of both alkene and alkyne units independently.Recently,great efforts have been made to establish efficient protocols to achieve optically active 1,4-enynes.Considering the enormous application potential of enantioenriched 1,4-enyne units but no related review on this topic has been described,here we aim to provide a comprehensive summary on the catalytic methods established for enantioselective constructions of these intriguing skeletons.According to the reaction types,this review is divided into five parts,including asymmetric allylic substitution,asymmetric propargylic substitution,asymmetric alkynylallylic substitution,asymmetric hydroalkynylation and asymmetric 1,2-addition of alkynes to conjugated imines or ketones.

Recent trends and developments in the asymmetric synthesis of profens

The profens belong to a class of nonsteroidal anti-inflammatory drugs(NSAIDs),which exert significant antiinflammatory,analgesic,antipyretic and other pharmacological effects.A considerable number of catalytic asymmetric strategies for the synthesis of enantioenriched profens have been introduced.Herein are outlined recent trends and developments of promising catalytic enantioselective systems for the generation of profens and their derivatives.According to the reaction type,we divided these transformations into three categories:Transition metal-catalyzed asymmetric hydrogenations,transition metal-catalyzed asymmetric cross-couplings and organocatalytic asymmetric transformations.Overviews of generic reaction mechanisms are presented.Ideally,this tutorial review will motivate further interest in the catalytic asymmetric synthesis of highly enantioenriched profens.

Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis of Axially Chiral Compounds

The well-defined conformational properties of axially chiral compounds bring extraordinary values to an assortment of bioactive molecules,advanced materials,organocatalysts as well as chiral ligands in asymmetric transformations.The demonstrated usefulness and untapped potential of axially chiral structural motifs stimulate increasing efforts to develop novel and efficient approaches for their preparation.In this regard,the chiral phosphoric acids broadly used in asymmetric Brønsted acid catalysis have shown high relevance for atroposelective synthesis as well.Our strong interest in reaction chemistry of atropisomers has established a rewarding research programme in our group.The course of studies will be recounted in this account,with discussion focused on the use of chiral phosphoric acids to catalyze construction of several key axially chiral structures such as BINAM,BINOL,NOBIN,arylquinones,SPINOL,arylpyrrole analogues and axially chiral alkenes.