Effects of nitrogen and alkene substitution on the PtCl2 catalyzed cycloisomerization of N-tethered 1,6-enyne precursors to the triple reuptake inhibitor GSK1360707

The effects of nitrogen and alkene substitution on the cycloisomerization of N-tethered 1,6-enynes into 3-azabicyclo[4.1.0]heptene precursors to the triple reuptake inhibitor GSK1360707 are described. In general, electron donating substituents proved beneficial both in terms of the reaction rate and chemoselectivity.     

Gas‐phase doubly charged complexes of cyclic peptides with copper in +1, +2 and +3 formal oxidation states: formation,structures and electron capture dissociation

Copper complexes with a cyclic D‐His‐β‐Ala‐L‐His‐L‐Lys and all‐L‐His‐β‐Ala‐His‐Lys peptides were generated by electrospray which were doubly charged ions that had different formal oxidation states of Cu(I), Cu(II) and Cu(III) and different protonation states of the peptide ligands. Electron capture dissociation showed no substantial differences between the D‐His and L‐His complexes. All complexes underwent peptide cross‐ring cleavages upon electron capture. The modes of ring cleavage depended on the formal oxidation state of the Cu ion and peptide protonation. Density functional theory (DFT) calculations, using the B3LYP with an effective core potential at Cu and M06‐2X functionals, identified several precursor ion structures in which the Cu ion was threecoordinated to pentacoordinated by the His and Lys side‐chain groups and the peptide amide or enolimine groups. The electronic structure of the formally Cu(III) complexes pointed to an effective Cu(I) oxidation state with the other charge residing in the peptide ligand. The relative energies of isomeric complexes of the [Cu(c‐HAHK + H)]²⁺ and [Cu(c‐HAHK ? H)]²⁺ type with closed electronic shells followed similar orders when treated by the B3LYP and M06‐2X functionals. Large differences between relative energies calculated by these methods were obtained for open‐shell complexes of the [Cu(c‐HAHK)]²⁺ type. Charge reduction resulted in lowering the coordination numbers for some Cu complexes that depended on the singlet or triplet spin state being formed. For [Cu(c‐HAHK ? H)]²⁺ complexes, solution H/D exchange involved only the N–H protons, resulting in the exchange of up to seven protons, as established by ultra‐high mass resolution measurements. Contrasting the experiments, DFT calculations found the lowest energy structures for the gas‐phase ions that were deprotonated at the peptide C_α positions. Copyright © 2012 John Wiley & Sons, Ltd.     

High-resolution mass spectrometry and hydrogen/deuterium exchange study of mitorubrin azaphilones and nitrogenized analogues

Azaphilones represent numerous groups of wild fungal secondary metabolites that exhibit exceptional tendency to bind to nitrogen atoms in various molecules, especially those containing the amine group. Nitrogenized analogues of mitorubrin azaphilones, natural secondary metabolites of Hypoxylon fragiforme fungus, have been detected in the fungal methanol extract in very low concentrations. Positive electrospray ionization interfaced with high-resolution mass spectrometry was applied for confirmation of the elemental composition of protonated species. Collision-induced dissociation (CID) experiments have been performed, and fragmentation mechanisms have been proposed. Additional information regarding both secondary metabolite analogue families has been reached by application of gas-phase proton/deuterium (H/D) exchanges performed in the collision cell of a triple quadrupole mass spectrometer. An incomplete H/D exchange with one proton less than expected was observed for both protonated mitorubrin azaphilones and their nitrogenized analogues. By means of the density functional theory, an appropriate explanation of this behavior was provided, and it revealed some information concerning gas-phase H/D exchange mechanism and protonation sites. Copyright ? 2012 John Wiley & Sons, Ltd.     

Direct determination of double bond position in long chain conjugated dienes by t.C4H9+ - chemical ionization mass spectrometry

t.C₄H₉⁺ - chemical ionization mass spectrometry of long chain conjugated dienes was shown to generate branched alkyl cations providing unambiguous location of the unsaturated system.     

Mécanismes de fragmentation en spectrométrie de masse par ionisation chimique. III—ions formés par cyclisation

Chemical ionization mass spectrometry of bifunctional organic molecules can induce fragmentation involving the formation of cyclic ions.     

Transposition de Cycles Satures en Spectrometrie de Masse III—Etude des Spectres en Basse Tension des Cyclanones

The fragmentation mechanism of cyclanones (cycloheptanone, cyclooctanone and some methylated or deuterated derivatives) was reinvestigated. All the peaks observed can be interpreted on the basis of a rearrangement of the molecular ion. This rearrangement is particularly important at low voltage.     

Cis/trans stereochemical effects in the negative chemical ionization/OH− mass spectra of strained-ring azabicycloalkanes using MIKE and CA/MIKE spectrometry

Stereospecific decomposition reactions of isomeric (cis and trans) deprotonated molecules from azabicycloalkane derivatives as azetidinols generated under negative chemical ionization (NCI)/OH^? have been examined using mass-analysed ion kinetic energy (MIKE) and collisional activation (CA)/MIKE spectra. These measurements together with the ones obtained on specifically labelled compounds enabled us to determine the origin of the stereochemical effects. The results indicate that the hydroxylic proton constitutes the preferential (?90%) site for the deprotonation process. Subsequent fragmentations of the deprotonated species observed in the second field-free region of a reversed geometry instrument are affected by the stereochemistry of the hydroxylic group. The isomer with the hydroxyl group in the cis position relative to the hydrogen at the ring junction mainly loses H₂O, while the trans isomer eliminates CH₃˙, both processes occurring with high specificity. Labelling studies indicate that two major pathways exist for the elimination of H₂O from the cis isomer and the loss of CH₃˙ from the trans isomer. The course of the reaction is determined by the ability of the stereoisomers to transfer a proton during the first decomposition step. When the size of the lactam ring is increased from a five-membered ring to a six- or seven-membered ring, these stereochemical effects tend to become less pronounced.     

Improved proton affinity measurements for proline and modified prolines using triple quadrupole and ion trap mass spectrometers

Proton affinity (PA) of compounds such as proline, cis-3-methylproline, cis-3-ethylproline, cis-3-isopropylproline and cis-3-isopentanylproline was determined by kinetic method with amines as the reference bases. The effective temperatures determined using ion trap and triple quadrupole mass spectrometers were found to be significantly different. In the case of the triple quadrupole instruments, the effective temperature depends significantly on the collision energy. The influence of the apparent basicity (GBapp) on the effective temperature may be used to estimate the difference in protonation entropy (DeltaDeltaS degrees) between the sample and reference compounds. In case of the ion trap mass spectrometer, the variation of the effective temperature as a function of the excitation amplitude is small, so it is difficult to account for the contribution of the entropy effects to the proton affinity value. A better estimation of the PA and DeltaDeltaS degrees values for the investigated molecules is obtained by combining the GBapp and Teff data pairs that are obtained from both the mass spectrometers.