Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders

In this study, the levels and composition of ceramides in brains of newborn mice lacking peroxisomes (Pex5-/-, Zellweger mice) were analyzed using normal-phase high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry (HPLC/APCI-MS). Total ceramide compositions were found to be comparable to that of control animals. However, a minor ceramide species, containing hexacosanoic/hexacosenoic acid as the amide fatty acid, was 9-fold increased. Also, in the sphingomyelin-derived ceramides this species was elevated. Subsequent analysis of extracts from fibroblasts of Pex5-/- mice and mice with a defective peroxisomal beta-oxidation (lacking D-specific multifunctional protein 2 (MFP2)), revealed, again, a similar rise in this particular ceramide. Further, this ceramide was elevated in human X-ALD fibroblasts as well. Whether C26:1/0-ceramide is linked to some of the pathology seen in Zellweger syndrome remains to be investigated. However, an increase in this sphingolipid can be considered as a diagnostic criterion for diseases caused by defects in peroxisome biogenesis or peroxisomal beta-oxidation.     

Relaxation processes in room temperature ionic liquids: the case of 1-butyl-3-methyl imidazolium hexafluorophosphate

A detailed investigation on the nature of the relaxation processes occurring in a typical room temperature ionic liquid (RTIL), namely, 1-butyl-3-methyl imidazolium hexafluorophosphate ([bmim][PF(6)]), is reported. The study was conducted using both elastic and inelastic neutron scattering over a wide temperature range from 10 to 400 K, accessing the dynamic features of both the liquid and glassy amorphous states. In this study, the inelastic fixed energy scan technique has been applied for the first time to this class of materials. Using this technique, the existence of two relaxation processes below the glass transition and a further diffusive process occurring above the glass-liquid transition are observed. The low temperature processes are associated with methyl group rotation and butyl chain relaxation in the glassy state and have been modeled in terms of two Debye-like, Arrhenius activated processes. The high temperature process has been modeled in terms of a Kohlraush-Williams-Watts relaxation, with a distinct Vogel-Fulcher-Tamman temperature dependence. These results provide novel information that will be useful in rationalizing the observed structural and dynamical behavior of RTILs in the amorphous state.     

Competing reaction pathways from α-halo-α-protioalkyl aryl sulfoxides initiated by organometallic reagents

The reactions of syn-1-haloethyl p-chlorophenyl sulfoxides (halogen = Cl, Br) with main-group organometallic reagents (n-BuMgCl, MeLi, n-BuLi, s-BuLi, and t-BuLi) in THF and PhMe solvents were examined. Product distributions were analyzed to determine the extent of competing sulfoxide ligand exchange, halogen-metal exchange, and deprotonation reaction pathways. A combination of t-BuLi in PhMe was optimal for initiation of sulfoxide ligand exchange from syn-1-chloroethyl p-chlorophenyl sulfoxide.     

An unusual dichotomy in the regioselectivity of a metal catalyzed versus thermal ene reaction

A Pd(+2) catalyzed cyclization of a 1,6-enyne complements a thermal Alder ene reaction; a rationale invoking a remote binding site is proposed.     

A reinvestigation of asymmetric induction in diels-alder reactions to chiral acrylates.

The chiral induction in the Diels-Alder addition $\text{1}$ → $\text{2}$, assessed reliably by ¹⁹F-NMR-spectroscopy of the endo-esters $\text{4}$, varied between 47 - 93% in favor of the 2-(R)-adducts $\text{2}$ depending on the auxiliary chiral group and the Lewis-acid catalyst.     

Stéréochimie des réactions de substitution des alcoxygermanes par les organolithiens et par les réactifs de Grignard

The reactions of organolithium reagents and Grignard reagents with optically active alkoxygermanes R₃GeOR′ have been studied [R₃GeOR′ = ()-i-PrPhNpGeOCH₃, ()-i-PrPhNPGeOMen and ()-MePhNpGeOMen]. Saturated reagents (e.g. butyllithium) give retention of configuration at germanium whilst unsaturated reagents (e.g. allyl- or benzyllithium) lead to inversion.     

Synthesis of the ladybug alkaloids (±)-propyleine and (±)-isopropyleine. Modification of the published structure of propyleine

The total syntheses of the ladybug alkaloids (±)-propyleine and (±)-isopropyleine are described. Evidence that the alkaloid propyleine is actually a rapidly interconverting mixture of propyleine and a previously unknown isomer isopropyleine is presented.     

A novel anthracenyl tagged protecting group for "phase-switching" applications in parallel synthesis

A new "phase-switching" protecting group 1 that facilitates the parallel synthesis of carboxylic acids, esters, and carboxamides is described. Its use permits chemistries to be performed in solution, which may be conveniently monitored with conventional analytical techniques, followed by subsequent immobilization onto a solid-phase support to aid compound purification. Carboxylic acids, esters, and carboxamides are then cleaved from the solid support following activation of the "safety-catch" and treatment with the desired nucleophile.     

One-carbon chain extension of esters to alpha-chloroketones: a safer route without diazomethane

The reaction of a variety of methyl esters with dimethylsulfoxonium methylide at 0-25 degrees C affords the chain-extended beta-keto dimethylsulfoxonium ylides. Subsequent treatment with hydrogen chloride in THF proceeds with loss of DMSO to afford the corresponding alpha-chloroketones. This sequence has been utilized to convert the methyl esters of CBZ-protected alanine and valine to the anti N-protected alpha-amino epoxides, which are important pharmaceutical intermediates. When the same protocol is applied to BOC-protected phenylalanine methyl ester, epimerization occurs so that the use of a more reactive aryl ester is required. This chemistry provides a practical route to alpha-chloroketones that avoids the use of toxic and explosive diazomethane.     

Femtosecond study of Cu(H(2)O) dynamics

The short-time nuclear dynamics of Cu(H(2)O) is investigated using femtosecond photodetachment-photoionization spectroscopy and time-dependent quantum wave packet calculations. The Cu(H(2)O) dynamics is initiated in the electronic ground state of the complex by electron photodetachment from the Cu(-)(H(2)O) complex, where hydrogen atoms are oriented toward Cu. Several time-resolved resonant multiphoton ionization schemes are used to probe the ensuing reorientation and dissociation. Immediately following photodetachment, the neutral complex is far from its minimum energy geometry and possesses an internal energy comparable to the Cu-H(2)O dissociation energy and undergoes both large-amplitude H(2)O motion and dissociation. Dissociation is observed to occur on three distinct time scales: 0.6, 8, and 100 ps. These results are compared to the results of time-dependent J=0 wave packet calculations, propagating the initial anion vibrational wave functions on the ground-state potential of the neutral complex. An excellent agreement is obtained between the experimental results and the ionization signals derived from the calculated probability amplitudes. Related experiments and calculations are carried out on the Cu(D(2)O) complex, with results very similar to those of Cu(H(2)O).