Enantioselective surface chemistry of R-2-bromobutane on Cu(643)R&S and Cu(531)R&S

The enantioselective surface chemistry of chiral R-2-bromobutane was studied on the naturally chiral Cu(643)R&S and Cu(531)R&S surfaces by comparing relative product yields during temperature-programmed reaction spectroscopy. Molecularly adsorbed R-2-bromobutane can desorb molecularly or debrominate to form R-2-butyl groups on the surfaces. The R-2-butyl groups react further by beta-hydride elimination to form 1- or 2-butene or by hydrogenation to form butane. Temperature-programmed reaction spectroscopy was used to quantify the relative yields of the various reaction products. At low coverages of R-2-bromobutane on Cu(643)R&S and Cu(531)R&S, the surface chemistry is not enantioselective. At monolayer coverage, however, the product yields indicate that the R-2-bromobutane decomposition reaction rates are sensitive to the handedness of the two chiral surfaces. The impact of surface structure on enantioselectivity was examined by studying the chemistry of R-2-bromobutane on both Cu(643)R&S and Cu(531)R&S. The selectivity of R-2-bromobutane desorption versus debromination is enantiospecific and differs significantly from Cu(643) to Cu(531). The selectivity of the R-2-butyl reaction by beta-hydride elimination versus hydrogenation is only weakly enantiospecific and is similar on both the Cu(643) and Cu(531) surfaces. These results represent the first quantitative observations of enantioselectivity in reactions with well-known mechanisms probed using a simple adsorbate on naturally chiral metal surfaces.     

Synthesis of R-(-)-imperanene from the natural lignan hydroxymatairesinol

A convenient and high yielding method for the synthesis of R-(-)-imperanene, starting from the readily available natural lignan hydroxymatairesinol from Norway spruce, was developed. Hydroxymatairesinol was degraded in strongly basic aqueous conditions to (E)-4-(4-hydroxy-3-methoxyphenyl)-2-(4-hydroxy-3-methoxyphenylmethyl)but-3-enoic acid, which was esterified and then reduced by LiAlH(4) to afford R-(-)-imperanene. The configuration at the crucial stereocenter was preserved in the synthesis, and the obtained product was identified by optical rotation measurements and chiral HPLC analyses as the R-(-)-enantiomer (ee 86-92%).     

New Key Building Block for Ixabepilone from R-(-)-Carvone

Russian Journal of Organic Chemistry - A synthetic approach is described for the transformation of R-(-)-carvone to methyl...     

Direct determination of S-(-)- and R-(+)-propranolol glucuronide in rat hepatic microsomes by RP-HPLC

Propranolol, available commercially as a racemic mixture, is a non-selective beta-adrenergic blocking agent used in the treatment of hypertension, angina pectoris and cardiac arrhythmias. We have developed and validated an RP-HPLC assay method for direct determination of R-(+)- and S-(-)-propranolol glucuronide in rat hepatic microsomes to investigate the enantioselectivity of propranolol glucuronidation metabolism. A baseline separation of propranolol glucuronide enantiomers was achieved on a 5 microm reversed-phase ODS column, with a mixture of phosphate buffer (pH 3.5, 0.067 mol/L) and methanol (55:45, v/v) as mobile phase. Ultraviolet detection was set at 220 nm, and p-nitrobenzoic acid was used as internal standard. The standard curve of assay for R-(+)- and S-(-)-propranolol glucuronide in spiked microsomal incubate showed good linearity throughout the concentration range from 0.50 to 20.0 micromol/L. The analytical method affords average recovery of 99.8 and 100.1% for R-(+)- and S-(-)-propranolol glucuronide, respectively. The method provides a high sensitivity and good precision for R-(+)- and S-(-)-propranolol glucuronide (RSD < 10%). The LOD was 0.15 micromol/L and the LOQ was 0.5 micromol/L (RSD < 8%, n = 5) for both R-(+)- and S-(-)-propranolol glucuronide. The method is simple, precise and accurate, and is suitable for quantifying the propranolol glucuronides enantiomers in rat hepatic microsomes.     

Luminescent heteronuclear Au(I)5Ag(I)8 complexes of [1,2,3-C6(C6H4R-4)3]3- (R = H, CH3, But) by cyclotrimerization of arylacetylides

Unusual AuI-AgI heterometallic complexes [Au5Ag8(mu-dppm)4{1,2,3-C6(C6H4R-4)3}(CCC6H4R-4)7]3+ (R = H 1, CH3 2, But 3) were isolated by reactions of polymeric silver arylacetylides (AgCCC6H4R-4)n with binuclear gold component [Au2(mu-dppm)2(MeCN)2]2+ (dppm = bis(diphenylphosphino)methane), in which cyclotrimerization of arylacetylide -CCC6H4R-4 affords trianion {1,2,3-C6(C6H4R-4)3}3- with an unprecedented mu5-bonding mode. Compounds 1(SbF6)3-3(SbF6)3 exhibit intense photoluminescence derived from an MLCT (Au5Ag8 --> CCC6H4R-4) transition, mixed with a metal cluster-centered excited states.     

Functionalization of single-walled carbon nanotubes with (R-)oxycarbonyl nitrenes

Sidewall functionalization of single-walled carbon nanotubes (SWCNTs) via the addition of (R-)oxycarbonyl nitrenes allows for the covalent binding of a variety of different groups such as alkyl chains, aromatic groups, dendrimers, crown ethers, and oligoethylene glycol units. Such additions lead to a considerable increase in the solubility in organic solvents such as 1,1,2,2-tetrachloroethane (TCE), dimethyl sulfoxide (DMSO), and 1,2-dichlorobenzene (ODCB). The highest solubilities of 1.2 mg/mL were found for SWCNT adducts with nitrenes containing crown ether of oligoethylene glycol moieties in DMSO and TCE, respectively. The presence of chelating donor groups within the addends allowed for the complexation of Cu(2+) and Cd(2+). Atomic force microscopy (AFM) and transmission electron microscopy (TEM) revealed that the functionalized tubes form thin bundles with typical diameters of 10 nm. The presence of thin bundles in solution is supported by (1)H NMR spectroscopy. The elemental composition of the functionalized SWCNT was determined by X-ray photoelectron spectroscopy (XPS). The use of Raman and electron absorption spectroscopy (UV/Vis-nIR) showed that the electronic properties of the SWCNTs are mostly retained after functionalization, indicating a low degree of addition within this series of SWCNT derivatives.     

Highly diastereoselective Diels-Alder cycloadditions of 9R-(1-methoxyethyl)anthracene with p-benzoquinone

Diels-Alder cycloadditions of p-benzoquinone with 9R-(1-methoxyethyl)anthracene provides a 60:40 ratio of cycloadducts when heated at reflux in xylene. Mechanistic studies to explore the origins of this selectivity have shown that at lower temperatures the kinetic product predominates, giving a 96:4 ratio of cycloadducts.     

Total syntheses of enantiomerically enriched R-(+)- and S-(-)-deplancheine

Total syntheses of indoloquinolizidine alkaloid (+/-)-, R-(+)-, and S-(-)-deplancheine are described here. The synthesis features an enantioselective intramolecular formal aza-[3 + 3] cycloaddition for the construction of the quinolizidine CD-ring. This application serves to introduce a new synthetic strategy for the synthesis of indoloquinolizidine alkaloids.     

Synthesis of 2-amino-5-(5R-1,2,4-oxadiazolyl-3)-1,3,4-oxadiazoles

The interaction of 2-amino-1,3,4-oxadiazole-5-carboxamidoxime with nitriles in the presence of ZnCl₂ and HCl or with trichloroacetic anhydride affords 2-amino-5-(5R-1,2,4-oxadiazolyl-3)-1,3,4-oxadiazoles. Their reactions with N-nucleophiles have been studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2100–2103, December, 1993.     

Phase equilibria of imidazolium ionic liquids and the refrigerant gas, 1,1,1,2-tetrafluoroethane (R-134a)

A number of applications with ionic liquids (ILs) and hydrofluorocarbon gases have recently been proposed. Detailed phase equilibria and modeling are needed for their further development. In this work, vapor–liquid equilibrium, vapor–liquid–liquid equilibrium, and mixture critical points of imidazolium ionic liquids with the hydrofluorocarbon refrigerant gas, 1,1,1,2-tetrafluoroethane (R-134a) was measured at temperatures of 25 °C, 50 °C, 75 °C and pressure up to 143 bar. The ionic liquids include 1-hexyl-3-methyl-imidazolium bis(trifluoromethylsulfonyl)amide ([HMIm][Tf₂N]), 1-hexyl-3-methyl-imidazolium hexafluorophosphate ([HMIm][PF₆]), and 1-hexyl-3-methyl-imidazolium tetrafluoroborate ([HMIm][BF₄]). The effects of the anion and cation on the solubility were investigated with the anion having greatest impact. [HMIm][Tf₂N] demonstrated the highest solubility of R-134a. The volume expansion and molar volume were also measured for the ILs and R-134a. The Peng–Robinson Equation of State with van der Waals 2-parameter mixing rule with estimated IL critical points were employed to model and correlate the experimental data. The models predict the vapor–liquid equilibrium and vapor–liquid–liquid equilibrium pressure very well. However, the mixture critical points predictions are consistently lower than experimental values.     

Proton transfer to nickel-thiolate complexes. 1. Protonation of [Ni(SC(6)H(4)R-4)(2)(Ph(2)PCH(2)CH(2)PPh(2))] (R = Me, MeO, H, Cl, or NO(2))

The kinetics of the equilibrium reaction between [Ni(SC(6)H(4)R-4)(2)(dppe)] (R= MeO, Me, H, Cl, or NO(2); dppe = Ph(2)PCH(2)CH(2)PPh(2)) and mixtures of [lutH](+) and lut (lut = 2,6-dimethylpyridine) in MeCN to form [Ni(SHC(6)H(4)R-4)(SC(6)H(4)R-4)(dppe)](+) have been studied using stopped-flow spectrophotometry. The kinetics for the reactions with R = MeO, Me, H, or Cl are consistent with a single-step equilibrium reaction. Investigation of the temperature dependence of the reactions shows that DeltaG = 13.6 +/- 0.3 kcal mol(-)(1) for all the derivatives but the values of DeltaH and DeltaS vary with R (R = MeO, DeltaH() = 8.5 kcal mol(-)(1), DeltaS = -16 cal K(-)(1) mol(-)(1); R = Me, DeltaH() = 10.8 kcal mol(-)(1), DeltaS = -9.5 cal K(-)(1) mol(-)(1); R = Cl, DeltaH = 23.7 kcal mol(-)(1), DeltaS = +33 cal K(-)(1) mol(-)(1)). With [Ni(SC(6)H(4)NO(2)-4)(2)(dppe)] a more complicated rate law is observed consistent with a mechanism in which initial hydrogen-bonding of [lutH](+) to the complex precedes intramolecular proton transfer. It seems likely that all the derivatives operate by this mechanism, but only with R = NO(2) (the most electron-withdrawing substituent) does the intramolecular proton transfer step become sufficiently slow to result in the change in kinetics. Studies with [lutD](+) show that the rates of proton transfer to [Ni(SC(6)H(4)R-4)(2)(dppe)] (R = Me or Cl) are associated with negligible kinetic isotope effect. The possible reasons for this are discussed. The rates of proton transfer to [Ni(SC(6)H(4)R-4)(2)(dppe)] vary with the 4-R-substituent, and the Hammett plot is markedly nonlinear. This unusual behavior is attributable to the electronic influence of R which affects the electron density at the sulfur.     

The addition reaction of acrylonitrile and methylacrylate toN-(5R-1,3,4-thiadiazol-2-yl)dithiocarbamates

A new type of dithiocarbamic acid derivatives,S-(2-X-ethyI) ethers ofN-(5R-1,3,4-thiadiazol-2-yl)-dithiocarbamic acids (X = CN, COOMe), has been synthesized by the reaction of sodiumN-(1,3,4-thiadiazol-2-yl) dithiocarbamates with acrylonitrile and methylacrylate.Deceased.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 749–750, April, 1994.     

Determination of the solubility,dissolution enthalpy and entropy of R-(+)-2-(4-hydroxyphenoxy) propanic acid in different solutions

The solubilities of R-(+)-2-(4-hydroxyphenoxy) propanic acid in acetone, ethyl acetate, acetonitrile, glycol ether, DMF, MIBK, n-butyl alcohol, THF and pyridine were measured at temperatures ranging from 273.15 K to 323.15 K at atmospheric pressure using a laser detecting system. First, the solubility data of R-(+)-2-(4-hydroxyphenoxy) propanic acid in selected solution were compared by the solubility parameter. Then, the solubility data were correlated by the Buchowski–Ksiazczak λh equation and modified Apelblat equation. Compared with the Apelblat equation, the Buchowski–Ksiazczak λh equation can fit the solubility data well. The dissolution enthalpy, entropy and Gibbs free energy of R-(+)-2-(4-hydroxyphenoxy) propanic acid were predicted by the van’t Hoff and Gibbs equation.     

Linear and nonlinear circular dichroism of R-(+)-3-methylcyclopentanone

Linear and nonlinear circular dichroism of R-(+)-3-methylcyclopentanone (R-3MCP) is reported in the gas and liquid phases. Measurements of (2+1) resonance-enhanced multiphoton ionization circular dichroism (REMPICD) for nozzle-jet expanded molecular beams of the equatorial conformer of R-3MCP are presented. Monitoring either mass-selected cations or photoelectrons produced via (2+1) REMPI through the n --> 3s Rydberg transition yielded a REMPICD of +1.5+/-0.5% [REMPICD identical with 2(I(L)-I(R))(I(L)+I(R))], where I(L/R) refers to the ion/electron signal for left/right circularly polarized light. A racemic mixture of 3-methylcyclopentanone showed no significant CD; however, the signal fluctuations were much larger than that observed for the resolved R-(+)-3-methylcyclopentanone as might be expected for the small number of ions produced from slightly unequal numbers of enantiomers in each laser shot. Gas phase, vibrationally resolved, one-photon CD for vapor phase R-(+)-3-methylcyclopentanone (i.e., admixture of five axial and equatorial forms) was measured to be approximately 0 and -0.004 at photon energies corresponding to the one- (nonresonant) and two-(3s resonance) photon energy levels. The one-photon CD (of the room temperature population of conformers) at an energy corresponding to the ionization step was measured previously to be approximately +0.0011 which is of the same sign as the REMPICD. The first step is also near a positive CD region. This suggests that the (2+1) REMPICD is determined primarily by both the initial and continuum steps. The one-photon CDs for the equatorial and axial forms of 3MCP are calculated, using GAUSSIAN03, to be approximately equal but having opposite sign for the transitions of interest. The CD for 3MCP in cyclohexane is found to be strongly temperature dependent as a result of the presence of both the axial and equatorial conformers. The energy difference between the two conformers is determined from a van't Hoff plot of these data to be 3.50+/-0.05 kJ/mole in cyclohexane and is approximately 1 kJ/mole smaller than measurements employing other methods.     

光谱法研究R-(+)-萘普生与DNA的相互作用

采用荧光光谱及紫外光谱法研究了R-(+)-萘普生与DNA相互作用的光谱特性.结果表明:DNA的加入使R-(+)-萘普生的紫外光谱产生减色、红移效应;荧光光谱发生了一定程度的猝灭.R-(+)-萘普生与DNA之间的作用主要是嵌插作用,它们之间的结合常数KA=1.236×104L·mol-1,结合位点数n=0.98.     

Evaluation of a hydrazide-linked alpha1-acid glycoprotein chiral stationary phase: separation of R- and S-propranolol

The binding and chiral separation of R- and S-propranolol was investigated on a new type of alpha1-acid glycoprotein (AGP) column. This column was prepared through the controlled and mild oxidation of AGP, followed by the immobilization of this protein to hydrazide-activated silica. The effects of temperature, pH, ionic strength, and organic modifiers on the retention and separation of R- and S-propranolol were investigated on this column. Both the association equilibrium constants and number of binding sites for R/S-propranolol on the AGP column were found to increase with temperature and affect the measured retention factors for these compounds. Regarding the other factors, a change in the organic modifier concentration was found to give the largest change in retention and separation. It was found through these studies that both coulombic and hydrophobic interactions played important roles in determining the retention of R- and S-propranolol on the AGP column. The efficiency and separation impedance of this system were also considered. Under the final optimum conditions identified in this study, it was possible to separate R- and S-propranolol with a resolution of greater than 1.38 in less than 5 min on a 4.1 mm I.D. x 5 cm column.     

Synthesis of R-(-)-2-ethyl-N-benzyl (benzo-monoaza-15-crown-5) and the Crystal Structure of Its Sodium Perchlorate Complex

A new complex of a chiral monoaza-crown ether, [R-(-)-2-ethyl-N-benzyl-4,7,10,13-tetraoxa-8,9-benzo-1-azacyclopentadec-8-ene...NaClO₄], has been prepared and studied by x-ray diffraction. The compound crystallizes in space group P2₁ with cell dimensions a = 8.721(1), b = 16.318(2), c = 8.905(1) Å, = 100.80(1)°. The sodium cation is heptacoordinated and located significantly out of the best plane of the macrocycle ring. The donor atoms of the macrocycle are in the half-chair arrangement.     

High-performance liquid chromatographic method for the simultaneous determination of R-(-)- and S-(+)-hexobarbital in rat plasma

The enantiospecific determination of R- and S-hexobarbital in rat plasma is described. The method involves liquid-liquid extraction of racemic hexobarbital from plasma, separation of the underivatized enantiomers by high-performance liquid chromatography on an alpha 1-acid glycoprotein column and ultraviolet detection. The mobile phase consists of a phosphate buffer (pH 5.4) containing 0.4% 2-propanol as organic modifier. An alpha 1-acid glycoprotein guard column is used to increase the lifetime of the analytical column. Heptabarbital is the achiral internal standard. With detection limits of ca. 0.05 microgram/ml for both R- and S-hexobarbital, the assay is suitable for pharmacokinetic studies of the enantiomers in rats.     

High Performance Liquid Chromatoraphic Determination of R-831, A New Antiallergic Agent,in Dogs and Humans

Abstract

A simple, selective and sensitive HPLC method has been developed to measure R-831 levels in dogs and humans. It is an internal standard technique with a single step extraction and one wash. Samples are chromatographed on a reversed-phase system with ultraviolet detection. The lowest detectable concentration for plasma is 25 ng R-831/ml with a 1 ml sample and the linear range is 25–8000 ng R-831/ml. The lowest detectable concentration for urine is 250 ng R-831/ml with a 0.1 ml sample and the linear range is 250–8000 ng R-831/ml. This method has been used to quantitate levels of R-831 in bioavailability and toxicity studies in dogs, and in pharmacokinetic and efficacy studies in humans.     

Enantioselective synthesis of the key intermediate of the acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor (R-106578) using 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)-Ru(OAc)2 as a catalyst

Acidic segment of an acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, R-106578 was synthesized by enantioselective hydrogenation of the Z-olefine (9-(Z)) using (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP)-Ru(OAc)2 as a catalyst in methanol at 100 degrees C, 5 kgf/cm2 of H2 pressure. The requisite Z-olefine was prepared regioselectively via coumarin derivative (5).