Synthesis of stereoregular poly(alkyl malolactonates)

Optically pure methyl, ethyl, isopropyl, and benzyl (R)-malolactonate were prepared from (S)-(-)-malic acid and were polymerized in the bulk with tetraethylammonium benzoate as the initiator to yield high-molecular-weight, crystalline polymers. The optical purity of methyl and benzyl malolactonate was determined by ¹H NMR spectroscopy of the β-lactone complexed with a chiral europium shift reagent. Enantiomeric excesses of 100% were found (the experimental error was 3%). Optically active poly(β-malic acid) was obtained from optically active poly[benzyl (S)-malate] by catalytic hydrogenolysis of the pendent benzyl esters. Ethyl and benzyl (R)-malolactonate were also copolymerized, and the benzyl esters of the resulting copolymer were converted into carboxylic acid units by hydrogenolysis.     

Revision of absolute configuration of enantiomeric (methylenecyclopropyl)carbinols obtained from (R)-(-)- and (S)-(+)-epichlorohydrin and methylenetriphenylphosphorane. Implications for reaction mechanism and improved synthesis of antiviral methylenecyclopropane analogues of nucleosides

Absolute configurations of enantiomeric methylenecyclopropanecarbinols obtained by reaction of (R)- and (S)-epichlorohydrin 5 with methylenetriphenylphosphorane or resolution of the corresponding oxaphospholane 6 via a salt with L-(+)-tartaric acid and subsequent Wittig transformation with formaldehyde were revised. The (-)-oxaphospholane 6 has the S,S and (-)-(methylenecyclopropyl)carbinol (4) the R configuration. The configurations of (+)-6 and (+)-4 are then R,R and S, respectively. These assignments are in accord with an initial attack of phosphorane at the oxirane ring of epichlorohydrin. An improved preparation of key enantiomeric intermediates (R)-1a and (S)-1a, important for synthesis of antiviral purine methylenecyclopropane analogues of nucleosides, is also described.     

Configurational studies on 2-[∝-(2-ethoxyphenoxy)benzyl] morpholine fce 20124

The relative configuration of the two diastereoisomers of (±)2-[?-(2-ethoxyphenoxy)benzyl] morpholine is determined by a synthesis involving regio and stereo specific reactions. (RS,RS) diastereoisomer FCE 20124 was separated into its (+) and (-) enantiomers both by crystallization of the optically active mandelate salt and by a multi-step synthesis from (+)-(2S,3R)-3-phenylglycidic acid.     

Poly(α-isobutyl-β-D,L-aspartate)s: Polymerization effects on configuration and crystal structure of the stereocopolymers

Different polymerization methods were used for the preparation of poly(α-isobutyl-β-D ,L -aspartate)s containing variable ratios of D - to L -aspartic units and the microstructure of the resulting stereocopolymers was examined by NMR spectroscopy. Anionic ring-opening polymerization in solution of enantiomeric mixtures of α-isobutyl-β-D - and L -aspartalactams was found to proceed stereoselectively rendering block copolymers composed of right- and left-handed helical sequences. Configurationally statistical copolymers were obtained instead when the enantiomeric lactam mixtures were polymerized in the bulk. Random stereocopolymers could be prepared also by polycondensation in solution of mixtures of pentachlorophenyl α-isobutyl-β-D and -L -aspartates. The conformation in solution and the crystal structure of the resulting copolymers were investigated in connection with their stereochemical configuration and these features compared with those displayed by optically pure poly(α-isobutyl-β-L -aspartate). © 1996 John Wiley & Sons, Inc.     

Liquid Chromatographic Resolution of Enantiomeric Dipeptides on the Chiral Stationary Phase Derived from (S)-1-(6,7-Dimethyl-1-naphthyl)isobutylamine

Abstract

Liquid chromatographic resolution of fifteen enantiomeric dipeptide methyl esters as their N-3,5-dinitrobenzoyl derivatives was investigated on the chiral stationary phase (CSP) derived from (S)-1-(6,7-dimethyl-1-naphthyl)isobutylamine. The four stereoisomers present in each dipeptide derivative were observed to be separated quite well with the (R,R) isomer being eluted first. The separation factors for two enantiomeric pairs such as (R,R)/(S,S) and (R,S)/(S,R) and the elution orders are explained by two competing “opposite-sense” chiral recognition mechanisms.     

Enantioselective synthesis of (S)-(+)-pantolactone

[reaction: see text] The Prins reaction of a chiral alkylidene morpholinone derived from (1R,2S)-ephedrine and 3-methyl-2-oxobutanoic acid proceeds with good diastereoselectivity to generate a spiro bis-acetal. Lewis acid mediated diastereoselective reductive cleavage of the spiro acetal and subsequent removal of the ephedrine portion generates a alpha-hydroxy-gamma-methoxy carboxamide which is readily converted to (S)-(+)-pantolactone with high enantiomeric excess.     

A Validated Chiral HPLC Method for the Determination of Enantiomeric Purity of R-β-amino-β-(4-methoxyphenyl) Propionic Acid

A normal phase chiral LC method for chiral purity evaluation of β-amino-β-(4-methoxyphenyl) propionic acid was developed on donor–acceptor (pirkle) column. The chiral stationary phase used was a 250 × 4.6 mm (R, R) Whelk-01 with 5 μm particle size, which was accompanied with a 1 cm long guard column. The “hybrid” pi-electron donor–acceptor based stationary phase (R, R) Whelk-01 was found to be enantiomeric selective for (R) and (S) enantiomers of β-amino-β-(4-methoxyphenyl) propionic acid with a resolution >2.5. The concentration of 2-propanol and TFA in the mobile phase plays an important role on the chrmatographic efficiency and resolution between the enantiomers. The limit of detection and limit of quantification of (S) enantiomer was 0.3 and 1.0 μg mL^-1 for 20 μL injection volume. The percentage RSD of the peak area of six replicate injections of (S) enantiomer at LOQ concentration was 4.5. The percentage recovery of (S) enantiomer from (R) enantiomer samples ranged from 92 to 100. The test solution was observed to be stable up to 24 h after the preparation. The developed method was also checked by different analysts and on different lots of columns, reagents and it was proved to be rugged. The developed normal phase chiral LC method can be used for the determination of the enantiomeric purity of R-β-amino-β-(4-methoxyphenyl) propionic acid.     

A New Convenient Method for the Resolution of 1, 1''''-Binaphthalene-2, 2''''-diol Via a Phosphite Using (-)-Menthol as Resolving Agent

Optically active 1,1-binaphthalene-2, 2-diol has become a quite important chiral source in different fields of chirotechnology, especially in asymmetric synthesis1. Its synthesis and resolution has been extensively studied and various resolution methods have been reported2. Among the reported resolution methods, the following three, namely, via the formation of phosphoric acid derivatives3, boric acid derivatives4 and inclusion complexes5, are the most important. OHOH+_( )-1(-)-(S)-1(+)-(R)…     

Stereochemical aspects of the controlled ring-opening polymerization of chiral cyclic esters

The stereochemical aspects of controlled polymerization of lactide and β-butyrolactone are discussed. The physicochemical and thermal properties of these polymers are shown to be depending on the stereochemical structure of the macromolecular chain. Different types of processes involving change of enantiomeric composition in the course of the polymerization reaction are examined in function of different initiators used. The formation of stereocomplexes from stereocopolymers of various enantiomeric compositions is reported.     

A general enantioselective approach to jasmonoid fragrances: synthesis of (+)-(1R,2S)-methyl dihydrojasmonate and (+)-(1R,2S)-magnolione

Methyl dihydrojasmonate 1 and magnolione 3 are of both academic and industrial interest. In this paper, we describe a flexible, high-yielding route to diastereomerically pure (+)-cis-(1R,2S)-methyl dihydrojasmonate 1 and the first synthesis of (+)-cis-(1R,2S)-magnolione 3, both with enantiomeric excesses up to 93%. The two syntheses diverged from the same advanced intermediate 5, readily available from the enantioenriched hydroxymethyl delta-lactone (-)-(3aS,4S,6aR)-6. The olfactory properties of (1R,2S)-1 and (1R,2S)-3 are reported.     

Absolute Conformation and Configuration of (2S, 3S)-3-Acetoxy-5-(dimethylaminoethyl)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one Chloride (Dilthiazem Hydrochloride)

Resolution of racemic cis-3-(2-aminophenylthio)-2-hydroxy-3-(4-methoxyphenyl) propionic acid ( 2 ) via the cinchonidine salt 3 , and brucine salt 4 , isolation of the calcium salts (+)- and (?)- 5 , as well as their cyclization to enantiomeric 1,5-benzothiazepines (+)- and (?)- 1 , are described. X-Ray single-crystal analysis reveals (2S, 3S) absolute configuration of (+)- 1 on the basis of tentative comparison of CD data with those for the 1,4-benzodiazepine derivative (+)- 8 of known absolute configuration.     

Optically Active T-Butylphenylphosphinothioic Acid: Synthesis,Selected Structural Studies and Applications as a Chiral Solvating Agent

Abstract

Synthesis, structural studies and the use of the (?)-(S)- and (+)-(R) enantiomers of t-butylphenylphosphinothioic acid as a chiral solvating agent for the determination of enantiomeric purity is discussed. Systems that are the most extensively studied are emphasized.     

Synthesis of (R)-2-methyl-4-deoxy and (R)-2-methyl-4,5-dideoxy analogues of 6-phosphogluconate as potential inhibitors of 6-phosphogluconate dehydrogenase

The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid.     

Catalysis of oxo transfer to prochiral sulfides by oxovanadium(v) compounds that model the active center of haloperoxidases

The catalytic properties of a new class of chiral vanadium compounds--[(S,S,S)-VO(OMe)L1] (5), [(S,S)-VO(OMe)L2] (6), [(S,S)-VO(OMe)L3] (7), and [(R,R,R)-VO(OMe)L4] (8), as well as the system VO(OiPr)(3)/(R,R,R)-H(2)L4 [H(2)L1=(S,S)-bis(2-hydroxypropyl)-(S)-1-phenylethylamine, 1; H(2)L2=(S,S)-bis(2-hydroxypropyl)benzylamine, 2; H(2)L3=(S,S)-bis(2-hydroxypropyl)isopropylamine), 3; (H(2)L4)=(R,R)-bis(2-phenylethanol)-(R)-1-phenylethylamine, 4]--in the asymmetric oxidation of prochiral sulfides by organic hydroperoxides have been investigated. Particular attention has been paid to the factors that guide the discrimination between the two prochiral faces of the sulfides (methyl p-tolyl sulfide and benzyl phenyl sulfide), to steric implications stemming from the oxidant (cumyl hydroperoxide and tert-butyl hydroperoxide), and to the specific complex used. As an example, (S)-methyl p-tolyl sulfoxide was obtained in a 31 % enantiomeric excess by use of cumyl hydroperoxide as oxidant and complex 5 as the catalyst, after 150 min at 0 degrees C and with 100 % conversion of the sulfide. The crystal and molecular structures of 5 and 6 reveal the close relationship between these complexes and the active center of vanadate-dependent haloperoxidases: the vanadium is in a slightly distorted trigonal-bipyramidal environment with the nitrogen and the methoxy group in the axial positions, and the oxo and alkoxide functions of L2 and L3 are the plane. The presence and equilibrium situation of isomers of the catalysts in solution has been investigated by (51)V EXSY and variable-temperature multinuclear NMR spectroscopy. An intermediately formed peroxo (ROO(-)) vanadium complex was detected by (51)V NMR spectroscopy.     

Application of a radial compression column to the high-performance liquid chromatographic separation of the enantiomers of some 2-arylpropionic acids as their diastereoisomeric s-(-)-1-(naphthen-1-yl)ethylamines

The enantiomers of 2-phenylpropionic acid and four congeneric anti-inflammatory drugs were separated as their diastereoisomeric amides with S-(-)-1-(naphthen-1-yl)ethylamine by high-performance liquid chromatography using a silica-packed radial compression cartridge. The order of elution of the diastereoisomeric amides was always R, S or -, S before S,S or +,S. The conditions for the derivatization, using 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide as coupling agent, were optimized, and it was found that the addition of 1-hydroxybenzotriazole rendered the reaction quantitative. Good calibration curves were obtained for the quantitation and determination of the enantiomeric composition of 2-phenylpropionic acid in urine, and the application of the method to the study of the metabolism of this acid in vivo is described.     

Novel resolution of the anthracyclinone intermediate by the use of (2r, 3r)-(+)- and (2s, 3s)-(-).1,4-bis(4-chlorobenzyloxy)butane-2,3-diol: a simple and efficient synthesis of optically pure 4-demethoxydaunomycinone and 4-demethoxyadriamycinone

(±)-7-Deoxy-4-demethoxydaunomycinone((±)-3) was found to be cleanly resolved by forming a mixture of the diastereomereic acetals((-)-9and(+)-10 or(+)-9 and(-)-10)with the title vicinal-diol(+)-or ( )-5), affording optically pure (R)-( )-3. The resolving agents (( + )- and ( )-5) were readily synthesized from unnatural(2S,3S)-(-)-tartaric acid((-)-6)or D-(-)-mannitol and natural (2R,3R)-(+)-tartaric acid((+)6), respectively. The undesired enantiomer ((S)-(+ )-3) obtained by the optical resolution could be racemized by heating with trifluoromethanesulfonic acid in aq acetic acid. Optically pure (R)-3 was elaborated to optically pure (+)-4-demethoxydaunomycinone ((+)-2b) and (+)-demethoxyadriamycinone ((+)-2a) by featuring highly stereoselective ( ? 20:1) introduction of the OH group into the C₇-position as a key step.     

Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon

The absolute configuration of the more active (-)-enantiomer of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl hydrochloride from the same chiral building block, viz. (S)-(-)-cyclohexyl-3-hydroxy-3-phenylpropanoic acid. Both enantiomers of this chiral synthon were prepared by optical resolution of the corresponding racemate, employing (R)- and (S)-1-phenylethylamine, respectively, as resolving agents.     

Synthesis of orthogonally protected (R)- and (S)-2-methylcysteine via an enzymatic desymmeterization and Curtius rearrangement

A synthesis of differentially protected (R)- and (S)-2-methylcysteines is described. Monomethylation of dimethylmalonate followed by alkylation with tert-butylchloromethyl sulfide gave an achiral diester. Desymmeterization by selective hydrolysis of one ester with pig-liver esterase gave the acid in 97% chemical yield and 91% enantiomeric excess. Heating this acid with diphenylphosphoryl azide followed by 4-methoxybenzyl alcohol gave protected (R)-2-methylcysteine. Alternately, the acid and ester groups were interchanged and heated with diphenylphosphoryl azide followed by 4-methoxybenzyl alcohol, giving protected (S)-2-methylcysteine.     

Syntheses,Characterization and Stereochemistry of S - and R,S -Hydrogenmalato Dioxotungsten(VI)

Cis -dioxo hydrogenmalato tungstates(VI) j -Na 2 [WO 2 ( S -Hmal) 2 ]·4H 2 O 1 , and Na 2 [WO 2 ( R , S -Hmal) 2 ] 2 (H 3 mal = malic acid) have been prepared from the reactions of excess S- malic acid and R , S -malic acid respectively, with sodium tungstate at ambient temperature. Both complexes were characterized by elemental analyses, conductivity measurement, optical rotation, UV-Vis, IR and NMR spectroscopy. Complex 1 was obtained with predetermined helical chirality at the metal center for a j - cis -configuration, which is established by single crystal X-ray diffraction. The crystal is orthorhombic, space group P 2 1 2 1 2 1 , with unit cell parameters: a = 7.9545(6), b = 10.7440(8), c = 21.045(2)Å, V = 1798.6(2)Å 3 , Z = 4, D c = 2.215 g cm m 3 , F (000) = 1152, R = 0.031, R w = 0.034. Single crystal X-ray diffraction reveals that the cis- dioxo tungstate 1 is octahedrally coordinated by the S -malate through the deprotonated f -hydroxy and f -carboxylate groups, while the g -carboxylic acid groups remain uncomplexed.     

CEC enantioseparations on chiral monolithic columns: a study of the stereoselective degradation of (R/S)-dichlorprop [2-(2,4-dichlorophenoxy)propionic acid] in soil

For the study of the stereoselective degradation of the herbicide 2-aryloxipropionic acid dichlorprop (DCPP) in soil, a porous monolithic chiral column (100 microm id) was prepared by in situ copolymerization of glycidyl methacrylate, methyl methacrylate and ethylene glycol dimethacrylate in the presence of formamide and 1-propanol as the porogen solvents. Subsequently, the epoxide groups at the surface of the monolith were reacted with (+)-1-(4-aminobutyl)-(5R,8S,10R)-terguride as the chiral selector. Optimum conditions for the herbicide resolution by CEC were found using mobile phases consisting of acetic acid/triethylamine mixtures in ACN-methanol (9:1 v/v). Under these conditions fully separation of DCPP enantiomers in the presence of clofibric acid (internal standard) was achieved in about 5 min. Experiments on the incubation of rac-DCPP in soil at room temperature showed the herbicide undergone during 23 incubation days to a degradation to levels 相似文献