First enantioselective total synthesis of (-)-Centrolobine

[structure: see text] The first enantioselective total synthesis of (-)-Centrolobine is described. The key reaction is the synthesis of the cis-disubstituted tetrahydropyran framework by intramolecular cyclization of the enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute configuration of (-)-Centrolobine is proposed.     

Analysis of serotonin in brain microdialysates using capillary electrophoresis and native laser-induced fluorescence detection

Serotonin or 5-hydroxytryptamine (5-HT) is a major neurotransmitter in the central nervous system. In this work, a method for analyzing 5-HT in brain microdialysis samples using a commercially available capillary electrophoresis (CE) system has been developed. A pH-mediated in-capillary preconcentration of samples was performed, and after separation by capillary zone electrophoresis, native fluorescence of 5-HT was detected by a 266 nm solid-state laser. The separation conditions for the analysis of 5-HT in standard solutions and microdialysates have been optimized, and this method has been validated on both pharmacological and analytical bases. Separation of 5-HT was performed using a 80 mmol/L citrate buffer, pH 2.5, containing 20 mmol/L hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and +30 kV voltage. The detection limit was 2.5 x 10(-10) mol/L. This method allows the in vivo brain monitoring of 5-HT using a simple, accurate CE measurement in underivatized microdialysis samples.     

New evidence of confinement effects in mesoporous materials and the definition of confined Pitzer acentric factors

In the present work, the corresponding states principle is proposed as a new approach to clarify the comparison between adsorption-desorption isotherms obtained on porous solids. The applicability of this principle at the capillary critical point in adsorption-desorption isotherms is demonstrated. Deviations of the Clausius-Clapeyron curves in reduced coordinates are interpreted in terms of polarizability, and those are perfectly correlated using analogous Pitzer acentric factors in confined environments. New acentric factors are proposed to take confinement effects in mesoporous materials into account. Enthalpic excesses during capillary condensation could be predicted, and those are supported by calorimetric experiments.     

2-Trimethylsilylethyl sulfides in the von Braun cyanogen bromide reaction: selective preparation of thiocyanates and application to nucleoside chemistry

Mixed 2-(trimethylsilyl)ethyl sulfides were synthesized and used in the von Braun cyanogen bromide reaction for preparing selectively thiocyanates in high yield. We show here that this cleavage reaction is highly selective in methanol in comparison with the reaction of the corresponding non-silyl sulfide analogues. This reaction was applied to the synthesis of nucleosidic thiocyanates such as the new nucleosides 14 and 18 in the search for mechanism-based inhibitors of ribonucleoside diphosphate reductase and bioactive molecules. The selective cleavage is possible for sulfides bearing hydroxyl functions and aromatic rings. The reactions of cyanogen bromide as cyanating and brominating agent were observed for the first time under the same conditions with the naphthoxyhexyl 2-trimethylsilylethyl sulfide 7, which, treated with cyanogen bromide in dichloromethane, led selectively to the p-bromonaphthoxyhexyl thiocyanate 10 in 89% yield. Another reaction induced by cyanogen bromide was observed in dichloromethane with the 2-(trimethylsilylethyl)thio nucleoside 13, which gives the corresponding symmetrical disulfide 21 in good yield.     

Cross-coupling reactions of phenylmagnesium halides with fluoroazines and fluorodiazines

The first nickel-catalyzed cross-coupling reactions between fluoroarenes and aryl organometallics using commercially available ligands are described. The nickel-catalyzed cross-coupling reactions between aryl Grignard reagents and fluoroazines and -diazines occurred in THF at room temperature using commercially available 1,2-bis(diphenylphosphino)ethane, 1,3-bis(diphenylphosphino)propane, or 1,1'-bis(diphenylphosphino)ferrocene as ligand. Various fluoro substrates such as pyridines, diazines (pyrazine, pyridazine), benzodiazines (quinoxaline), and quinolines were successfully involved in the reaction with phenylmagnesium halides (phenylmagnesium chloride, 2-methoxyphenylmagnesium bromide, and 4-methoxyphenylmagnesium bromide). The conditions used also allowed the cross-coupling of 4-fluorotoluene with arylmagnesium reagents.     

The band 12 issue in the electron momentum spectra of norbornane: a comparison with additional Green's Function calculations and ultraviolet photoemission measurements

In continuation of a recent study of the electronic structure of norbornane [J. Chem. Phys., 2004, 121, 10525] by means of electron momentum spectroscopy (EMS), we present Green's Function calculations of the ionization spectrum of this compound at the ADC(3) level using basis sets of varying quality, along with accurate evaluations at the CCSD(T) level of the vertical (26.5 eV) and adiabatic (22.1 eV) double ionization thresholds under C(2v) symmetry. The obtained results are compared with newly recorded ultraviolet photoemission spectra (UPS), up to binding energies of 40 eV. The theoretical predictions are entirely consistent with experiment and indicate that, in a vertical depiction of ionization, shake-up states at binding energies larger than approximately 26.5 eV tend to decay via emission of a second electron in the continuum. A band of s-type symmetry that has been previously seen at approximately 25 eV in the electron impact ionization spectra of norbornane is entirely missing in the UPS measurements and theoretical ADC(3) spectra. With regard to these results and to the time scales characterizing electron-electron interactions in EMS (10(-17) s) as compared with that (10(-13) s) of photon-electron interactions in UPS, and considering the p-type symmetry of the electron momentum distributions for the nearest 1b(1) and 1b(2) orbitals, this additional band can certainly not be due to adiabatic double ionization processes starting from the ground electronic state of norbornane, or to exceptionally strong vibronic coupling interactions between cationic states derived from ionization of the latter orbitals. It is therefore tentatively ascribed to autoionization processes via electronically excited and possibly dissociating states.     

Formation of a stable cyano-bridged dinuclear iron cluster following oxidation of the superoxide reductases from Treponema pallidum and Desulfovibrio vulgaris with K(3)Fe(CN)(6)

Superoxide reductases catalyze the monovalent reduction of superoxide anion to hydrogen peroxide. Spectroscopic evidence for the formation of a dinuclear cyano-bridged adduct after K(3)Fe(CN)(6) oxidation of the superoxide reductases neelaredoxin from Treponema pallidum and desulfoferrodoxin from Desulfovibrio vulgaris was reported. Oxidation with K(3)Fe(CN)(6) reveals a band in the near-IR with lambda(max) at 1020 nm, coupled with an increase of the iron content by almost 2-fold. Fourier transform infrared spectroscopy provided additional evidence with CN-stretching vibrations at 2095, 2025-2030, and 2047 cm(-)(1), assigned to a ferrocyanide adduct of the enzyme. Interestingly, the low-temperature electronic paramagnetic resonance (EPR) spectra of oxidized TpNlr reveal at least three different species indicating structural heterogeneity in the coordination environment of the active site Fe ion. Given the likely 6-coordinate geometry of the active site Fe(3+) ion in the ferrocyanide adduct, we propose that the rhombic EPR species can serve as a model of a hexacoordinate form of the active site.     

Artificial metalloenzymes: (strept)avidin as host for enantioselective hydrogenation by achiral biotinylated rhodium-diphosphine complexes

We report on the generation of artificial metalloenzymes based on the noncovalent incorporation of biotinylated rhodium-diphosphine complexes in (strept)avidin as host proteins. A chemogenetic optimization procedure allows one to optimize the enantioselectivity for the reduction of acetamidoacrylic acid (up to 96% ee (R) in streptavidin S112G and up to 80% ee (S) in WT avidin). The association constant between a prototypical cationic biotinylated rhodium-diphosphine catalyst precursor and the host proteins was determined at neutral pH: log K(a) = 7.7 for avidin (pI = 10.4) and log K(a) = 7.1 for streptavidin (pI = 6.4). It is shown that the optimal operating conditions for the enantioselective reduction are 5 bar at 30 degrees C with a 1% catalyst loading.     

A stabilized formulation of IBX (SIBX) for safe oxidation reactions including a new oxidative demethylation of phenolic methyl aryl ethers

[reaction: see text] SIBX is a nonexplosive formulation of IBX that can be used as a suspension in a variety of standard organic solvents such as refluxing EtOAc and THF to oxidize safely alcohols into aldehydes and ketones. The use of hot THF is limited to the oxidation of allylic and benzylic alcohols. Most yields are comparable to those obtained with IBX or DMP. SIBX can also be used to perform oxygenative demethylation of 2-methoxyarenols into orthoquinones and catechols.