Kinetic study on extractive resolution of tropic acid by hydroxyethyl-β-cyclodextrin

Reactive extraction is proposed as a promising approach to the resolution of tropic acid (TA), where hydroxyethyl-β-cyclodextrin (HE-β-CD) is used as a selective extractant. The reaction between tropic acid and extractant occurred in the aqueous phase, and kinetic studies of reactive extraction have been investigated in a Lewis-type stirred cell. The batch experiments have been performed to study the process parameters affecting the extraction rate including agitation speed, interfacial area, pH value of aqueous phase, initial concentration of tropic acid enantiomers and initial concentration of extractant on the initial extraction rate. The kinetic equation of the forward rate was deduced at the experiment condition: r _TA+ = (4.041 × 10^?3)[TA₊][CD]²; r _TA? = (3.1234 × 10^?3)[TA_?][CD]².     

Asymmetric Synthesis of (-)-(2R,3R,6S)-Irnigaine

Introduction　　Asarelativelynewmemberofnaturalalkaloidswith2 ,6 disubstituted 3 piperidinolskeleton ,irnigaine 1wasisolatedfromthetubersofArisarumVulgare (Araceae)in1995byMelhaouiandBode .1Itsstructureandrelativeconfigurationswereelucidatedby1HNMRstudiesandtheabsoluteconfigurationwasproposedonthebasisofitsopti calrotation .1Soonafterthen ,Meyerandhisco workersreportedthefirstsynthesisof (- ) (2R ,3R ,6S) irni gaineandtheconfigurationconfirmation .Althoughtheirsynthesisroutewasshortan…     

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)-1-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.     

Synthesis of (1R,cis,αS)-cypermethrine via lipase catalyzed kinetic resolution of racemic m-phenoxybenzaldehyde cyanohydrin acetate

A technical scale preparation of optically active (1R,cis,αS)-cypermethrine 4 from racemic m-phenoxybenzaldehyde cyanohydrin acetate (RS)-1 and (1R,cis)-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid chloride (1R,cis)-3 is described. Key steps of the new procedure are a lipase catalyzed enantioselective transesterification of (RS)-1 with n-butanol and direct acylation of the mixture of (R)-1 and (S)-cyanohydrin (S)-2 with (1R,cis)-3 to give enantiomerically pure (1R,cis,αS)-4. The unchanged (R)-1 is removed from (1R,cis,αS)-4 by distillation, and is racemized with triethylamine to give (RS)-1 which is returned to the process. The total yield of (1R,cis,αS)-4 referred to (RS)-1 is 80%.     

Lipase catalyzed regio- and stereospecific hydrolysis: chemoenzymatic synthesis of both (R)- and (S)-enantiomers of α-lipoic acid

Native lipase of Candida rugosa (EC 3.1.1.3) enantioselectively and regiospecifically hydrolyses the n-butyl ester of 2,4-dithioacetyl butanoic acid either at the carboxylic acid terminus or at the α-thioacetate to provide enantiomerically pure (R)-2,4-dithioacetyl butyric acid and (S)-butyl 2-thio-4-thioacetyl butyrate (ee >98%) while the lipase modified by treatment with diethyl p-nitrophenyl phosphate attacks only the α-thioacetate giving enantiomerically pure (S)-butyl 2-thio-4-thioacetyl butyrate. These enantiomerically pure intermediates can be used as chiral building blocks to obtain both (S)- and (R)-enantiomers of α-lipoic acid and their analogues.     

Kinetic resolution of (±)-2,3-dihydro-3-methyl-4H-1,4-benzoxazines with (S)-naproxen

A very effective method for the preparation of the (S)-enantiomers of 2,3-dihydro-3-methyl- and 7,8-difluoro-2,3-dihydro-3-methyl-4H-1,4-benzoxazines (1a and 2a) was developed using (S)-(+)-naproxen acyl chloride as the chiral agent for kinetic resolution of racemates. This method enables one to obtain the (S)-enantiomers of benzoxazines 1a and 2a of high enantiomeric purity (99% ee) in nearly 50% yield, taking into account that the (R)-enantiomers are recycled after their racemisation.     

An NMR study of inclusion complexes formed by α-cyclodextrin and (R)- or (S)-α-lipoic acid

A ¹H NMR study that explored the ability of α-cyclodextrin (α-CD) to preferentially bind (R)-α-lipoic acid is presented. The interaction between α-CD and (R)-α-lipoic acid was found to be stronger than that between α-CD and (S)-α-lipoic acid. Structures for the (R)-α-lipoic acid/α-CD and (S)-α-lipoic acid/α-CD inclusion complexes were constructed using restraints derived from ROESY spectra and MM2 molecular mechanics calculations. The models built for both complexes have the 1,2-dithiolane ring and the carboxyl moiety of α-lipoic acid oriented toward the secondary and primary hydroxy sides of α-CD, respectively.     

Co-crystal of (R,R)-1,2-cyclohexanediol with (R,R)-tartaric acid,a key structure in resolution of the (±)-trans-diol by supercritical extraction,and the related ternary phase system

A novel co-crystal of trans-(R,R)-1,2-cyclohexanediol and (R,R)-tartaric acid (with 1:1 molar ratio, 1) has been found to be a key crystalline compound in the improved resolution of (±)-trans-1,2-cyclohexanediol by supercritical fluid extraction. The molecular and crystal structure of this co-crystal, which crystallizes in orthorhombic crystal system (space group P2₁2₁2₁, a = 6.7033(13) Å, b = 7.2643(16), c = 24.863(5), Z = 4), has been solved by single crystal X-ray diffraction (R = 0.064). The packing arrangement consists of two dimensional layers of sandwich-like sheets, where the inner part is constructed by double layers of tartaric acids which hydrophilicity is “covered” on both upper and bottom side by cyclohexanediols with the hydrophobic cyclohexane rings pointing outward. Thus, a rather complex hydrogen bonding pattern is constructed. The relatively high melting point (133 °C) observed by both simultaneous TG/DTA and DSC, and the main features of FTIR-spectrum of 1 are explained by the increased stability of this crystal structure. DSC studies on binary mixtures of co-crystal 1 with (R,R)-1,2-cyclohexanediol or (R,R)-tartaric acid, revealed eutectic temperatures of T_eu = 100 or 131 °C, respectively. Between (S,S)-1,2-cyclohexanediol and (R,R)-tartaric acid a eutectic temperature of T_eu = 85 °C have also been observed. The phase relations have been confirmed by powder X-ray diffraction, as well.     

First enantioselective total synthesis of (S)-(−)-longianone

An efficient stereoselective synthesis of (S)-(?)-longianone was achieved from sugar derived 1,2-cyclopropanecarboxylate involving bromonium ion mediated solvolytic ring opening and a one-pot dehydrohalogenation, stereoselective intramolecular hetero Michael addition (IHMA) and ester hydrolysis as key steps.     

Enantioselective preparation of (2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids and some derivatives

(2R,3R)-(+)- and (2S,3S)-(−)-2,3-epoxy-2-methylbutanoic acids (epoxyangelic acids) were prepared from (Z)-2-methyl-2-butenoic acid using the Sharpless asymmetric epoxidation method in combination with the use of (−)- and (+)-menthol as chiral auxiliaries. Both substances, obtained in high enantiomeric excess, were characterized by spectroscopic and optical activity data. Their absolute configuration was determined by correlation with (R)-(+)-2-methyl-1,2-butanediol.     

Short syntheses of (S)-pipecolic acid, (R)-coniine,and (S)-δ-coniceine using biocatalytically-generated chiral building blocks

The kinetic resolutions of both (±)-N-(benzyloxycarbonyl-2-(hydroxymethyl)piperidine [(±)-5] and (±)-N-(tert-butoxycarbonyl)-2-(hydroxymethyl)piperidine [(±)-6] catalyzed by the enzyme acylase I from Aspergillus species (AA-I) afforded the chiral building blocks (S)-5 and (S)-6, respectively; which were used for the syntheses of the title natural products and derivatives of (S)-pipecolic acid. The syntheses were short (2–4 steps) and proceeded with satisfactory overall yield.     

Asymmetric Conjugate Addition of Alcohols to (R)-(-)-5-[(1R,2S,5R)-Menthyloxy]-2-(5H)-Furanone

(R)-(-y5-[(IR,2S,5R)-menthyloxy](1)isausefulchiralsynthonreadilypreparedonatWo-stepprocedure-l']FindingsoffuranoneringsexistingascomponentSofsomenaturalproductSI'laswellastheiractivereactivityl']havestimu1atedeXtensiveresearchofitSasymmetricreactionswhichincludeDiels-Alderreactions,l']l,3-dipo1arcycloadditions,['1Michaelauditionsl5]andconjugateedditionsofaminesl']andmercaPtans.g4:,::7f:7':theseadductsledtovariousmultifunctionalhomochiralbuildingblockssuchas2-alkyl-l,4-butanediols,I'l2-aI…     

Enantioselective synthesis of (2S,2′R)-erythro-methylphenidate

A new approach towards the enantioselective synthesis of (2S,2′R)-erythro-methylphenidate (1) is described. The key step in the synthesis utilizes Evans' 4-substituted-2-oxazolidinone chiral auxiliary to control the diastereofacial selectivity in the hydrogenation of enamine intermediate 6, yielding the hydrogenated product 7 with excellent diastereoselectivity. Methanolysis of 7 afforded 1 with excellent enantiopurity.     

Chiral phosphoric acid catalyzed enantioselective synthesis of β-amino-α,α-difluoro carbonyl compounds

A biphenol-based chiral phosphoric acid bearing a 9-anthryl group at each of the 3,3'-positions catalyzed the asymmetric Mannich-type reaction of N-Boc imine with difluoroenol silyl ethers in the presence of MS3A in THF to afford β-amino-α,α-difluoroketones in good yields and with excellent enantioselectivities. Optically pure 3,3-difluoroazetidin-2-one was readily synthesized from the Mannich-adduct.     

Synthesis of (S)-(+)-sotalol and (R)-(−)-isoproterenol via a catalytic enantioselective Henry reaction

A unified approach for the synthesis of (S)-(+)-sotalol and (R)-(?)-isoproterenol has been developed. The enantioselective Henry reaction of the appropriate aldehyde in the presence of a camphor-derived amino pyridine–Cu(II) complex was the key step of the synthesis. The reduction of the nitro group to give the corresponding amino alcohols followed by reductive alkylation of the amine provided the target products with high enantiomeric excesses.     

Regio- and stereoselective methods for the conversion of (2S,3R)-β-phenylglycidic acid esters to taxoids and other enantiopure (2R,3S)-phenylisoserine esters

A novel efficient method was proposed for the synthesis of enantiopure precursors of taxane-containing cytostatics, i.e., methyl esters of (2R,3S)- and (2S,3R)-N-benzoylphenylisoserine and similar taxoid esters. The method is based on the regio- and stereoselective hydrobromolysis of the corresponding trans-β-phenyl glycidate enatiomers, consecutive reactions of O-acylcarbamoylation of the obtained 3-bromohydrins, intramolecular cyclization to 4-phenyloxazolidin-2-one-5-carboxylic acid derivatives, and oxazolidinone ring opening.     

Synthesis and structural characterization of camphanates of (−)-(2S3S,3S) and (+)-(2S,3R)-4-Phenyl-3-bromo-2-butanol diastereoisomers

The X-ray crystal structures of (–)-syn-4-phenyl-3-bromo-2-butyl camphanate (I) and (+-anti-4-phenyl-3-bromo-2-butyl camphanate (II) have been determined. Thesyn diastereoisomer of bromohydrin has the (2S,3S) absolute configuration whereas theanti diastereoisomer has the (2S,3R) absolute configuration. The crystallized derivatives I and II have been obtained by the reaction of each stereoisomer of bromohydrin, synthesized by reduction with baker's yeast, with (1S)-camphanic chloride. Crystal data: (I) C₂₀H₂₅BrO₄:M _w: 409.32; orthorhombic,P2₁2₁2₁;a=11.245(3),b=12.086(1),c=14.512(4) å; Z=4; finalR=0.053 for 1819 observed reflections. (II) C₂₀H₂₅BrO₄;M _w=409.32; monoclinic, P2₁;a=11.352(1),b=6.378(1),c=14.255(2) å,=110.38(1);Z=2; finalR=0.045 for 1672 observed reflections.     

Diastereoselective palladium(0)-catalyzed azidation of 1-alkenylcyclopropyl esters: asymmetric synthesis of (−)-(1R,2S)-norcoronamic acid

Palladium(0)-catalyzed azidation of (1R,2S)-1-(1-alkenyl)2-methylcyclopropyl esters 10a,b proceeds with complete retention of configuration to provide, after reduction of the azide and oxidative cleavage of the allylic double bond, the (1R,2S)-norcoronamic acid 22 (>99% e.e.).