Phenylsulfonyl ene-allenes as efficient precursors to bicyclic systems via intramolecular [2 + 2]-cycloaddition reactions

Various phenylsulfonyl allene derivatives were prepared with double bonds tethered either to the alpha-position or the gamma-position of the allene. These substrates underwent a highly regio- and stereospecific thermal [2 + 2]-cycloaddition across the nonactivated cumulene double bond, forming distal cycloadducts (i.e., 57) in the case of alpha-tethered allenes and proximal adducts (i.e., 25) in the case of gamma-tethered allenes. The mechanistic rationale for the observed stereospecificity involves initial diradical formation, followed by a rapid ring closure to the more stable cis-fused ring system. The tether may be equipped with heteroatoms, allowing for the formation of fused heterocycles (e.g., 61), and the cycloaddition can be facilitated by the introduction of sterically bulky groups and/or by conformational rigidity to the tether. Other modes of cyclization were observed in the presence of sodium benzenesulfinate or Lewis acids, in which cases polar mechanisms prevail. The chemoselectivity is reversed for [4 + 2]-cycloadditions, which prefer instead to engage the vinyl sulfone moiety, independent of whether the tether is attached to the alpha- or gamma-position of the allene.     

Zur Synthese von fungizid wirksamen Isocamphanderivaten: Synthesen in der Isocamphanreihe, 34. Mitt.

Summary Some esters of isocamphenilanic acid (4) have been prepared and tested for their fungicidal and insecticidal activity. Esters of various acids with isocamphanyl ethylalcohol (5) have also been synthesized and included in the fungicidal/acaricidal/insecticidal screening programme. All esters bear a geminal dimethyl group at C-3 of the bicyclus which is important because of its shielding effect.

     

Gaseous alkyne ions

Using the relative abundance of metastable ions, collisional activation spectra, field ionization kinetic measurements, isotopic labelling, appearance energy and kinetic energy release data, it is shown that linear alkyne radical cations with more than six carbon atoms do not isomerize to equilibrating structures prior to decomposition. At the shortest ion lifetimes the molecular ions of linear alkynes decompose mainly by simple β-bond fission which allows an unequivocal localization of the triple bond. At medium ion lifetimes fragmentation occurs predominantly via a McLafferty rearrangement, while at long ion lifetimes competing alkyl losses prevail. These alkyl losses occur via cyclic intermediates leading to thermochemically stable cycloalkenyl ions. All these reactions occur with a high specificity with respect to the carbon and hydrogen atoms involved and are preceded by little or no hydrogen exchange reactions.     

2,6-dicyano-1,5-dimethylsemibullvalene as a probe for homoaromatic molecules of the Dewar-Hoffman type

The 2,6-dicyano-1,5-dimethylsemibullvalene (2d) synthesized via the bicyclo[3.3.0]octanedione 7 exists as a classical ground state which is lower in energy by less than 5 kcal/mole than the homoaromatic transition of the Cope rearrangement of 2d.     

Prerequisites for peptidomic analysis of blood samples: II. Analysis of human plasma after oral glucose challenge -- a proof of concept

Mass spectrometric plasma analysis for biomarker discovery has become an exploratory focus in proteomic research: the challenges of analyzing plasma samples by mass spectrometry have become apparent not only since the human proteome organization (HUPO) has put much emphasis on the human plasma proteome. This work demonstrates fundamental proteomic research to reveal sensitivity and quantification capabilities of our Peptidomics technologies by detecting distinct changes in plasma peptide composition in samples after challenging healthy volunteers with orally administered glucose. Differential Peptide Display (DPD) is a technique for peptidomics studies to compare peptides from distinct biological samples. Mass spectrometry (MS) is used as a qualitative and quantitative analysis tool without previous trypsin digestion or labeling of the samples. Circulating peptides (< 15 kDa) were extracted from 1.3 mL plasma samples and the extracts separated by liquid chromatography into 96 fractions. Each fraction was subjected to MALDI MS, and mass spectra of all fractions were combined resulting in a 2D-display of > 2,000 peptides from each sample. Endogenous peptides that responded to oral glucose challenge were detected by DPD of pre-and post-challenge plasma samples from 16 healthy volunteers and subsequently identified by nESI-qTOF MS. Two of the 15 MS peaks that were significantly modulated by glucose challenge were subsequently identified as insulin and C-peptide. These results were validated by using immunoassays for insulin and C-peptide. This paper serves as a proof of principle for proteomic biomarker discovery down to the pM concentration range by using small amounts of human plasma.     

A new route to achiral and chiral 1,2-bis(phosphino)ethanes, 1-arsino-2-phosphinoethanes, and 1,3-bis(phosphino)propanes and the molecular structure and catalytic activity of some rhodium(I) complexes derived thereof

A series of unsymmetrical 1,2-bis(phosphino)ethanes R(2)PCH(2)CH(2)PR'(2) and 1-arsino-2-phosphinoethanes R(2)AsCH(2)CH(2)PR'(2) mainly with bulky substituents R and R' were prepared from the cyclic sulfate by stepwise cleavage of the carbon-oxygen bonds by LiPR(2) and LiPR'(2) or LiAsR(2) and LiPR'(2), respectively. Analogously, racemic mixtures of R(2)PCH(2)CH(Me)PPh(2)(R =iPr, Cy ) as well as the enantiomers (R)-, (R)- and (R)-tBu(2)PCH(2)CH(Me)PPh(2)(R)- were obtained from the corresponding unsymmetrical cyclic sulfates and (S)-. On a similar route, the racemates of the 1,3-bis(phosphino)propanes R(2)PCH(2)CH(2)CH(Me)PPh(2)(R =iPr, tBu ), optically pure (R)- and (S,S)-iPr(2)PCH(Me)CH(2)CH(Me)PPh(2)(S,S)- were prepared. The reaction of [[RhCl([small eta](4)-C(8)H(12))](2)] with chelating ligands L-L, where L-L is R(2)PCH(2)P(men)(2)(R =iPr, Ph; men =(1S,2R,5S)-menthyl), Cy(2)AsCH(2)P(men)(2), or (R)-, (R)-, (R)-, (R)- and (S,S)-, in the presence of AgPF(6), gave the complexes [Rh(eta(4)-C(8)H(12))(L-L)]PF(6) which were used as pre-catalysts in the hydrogenation of the methyl ester of alpha-acetamidocinnamic acid (ACM). Depending on L-L, the solvent, the temperature and the pressure of H(2), optical yields of up to 69% ee were achieved. For two of the rhodium complexes, and, the molecular structures were determined by X-ray crystallography.     

Computational study on mechanistic details of the aminoethanol rearrangement catalyzed by the vitamin B12-dependent ethanolamine ammonia lyase: His and Asp/Glu acting simultaneously as catalytic auxiliaries

The rearrangement of aminoethanol catalyzed by ethanolamine ammonia lyase is investigated by computational means employing DFT (B3LYP/6-31G) and ab initio molecular orbital theory (QCISD/cc-pVDZ). The study aims at providing a detailed account on various crucial aspects, in particular a distinction between a direct intramolecular migration of the partially protonated NH(2) group vs elimination of NH(4)(+). Three mechanistic scenarios were explored: (i) According to the calculations, irrespective of the nature of the protonating species, intramolecular migration of the NH(3) group is energetically less demanding than elimination of NH(4)(+). However, all computed activation enthalpies exceed the experimentally derived activation enthalpy (15 kcal/mol) associated with the rate-determining step, i.e., the hydrogen abstraction from the 5'-deoxyadenosine by the product radical. For example, when imidazole is used as a model system for His interacting with the NH(3) group of the substrate, the activation enthalpy for the migration process amounts to 27.4 kcal/mol. If acetic acid is employed to mimic Asp or Glu, the activation enthalpy is somewhat lower, being equal to 24.2 kcal/mol. (ii) For a partial deprotonation of the substrate 2 at the OH group, the rearrangement mechanism consists of the dissociation of an NH(2) radical from C(2) and its association at C(1) atom. For all investigated proton acceptors (i.e., OH(-), HCOO(-), CH(3)COO(-), CH(2)NH, imidazole), the activation enthalpy for the dissociation step also exceeds 15 kcal/mol. Typical data are 20.2 kcal/mol for Ac(-) and 23.8 kcal/mol for imidazole. (iii) However, in a synergistic action of partial protonation of the NH(2) group and partial deprotonation of the OH group by the two conceivable catalytic auxiliaries Asp/Glu and His, the activation enthalpy computed is compatible with the experimental data. For imidazole and acetate as model systems, the activation enthalpy is equal to 13.7 kcal/mol. This synergistic action of the two catalytic groups is expected to take place in a physiologically realistic pH range of 6-9.5, and the present computational findings may help to further characterize the yet unknown structural details of the ethanolamine ammonia lyase's active site.     

Comparative analysis of local spin definitions

This work provides a survey of the definition of electron spin as a local property and its dependence on several parameters in actual calculations. We analyze one-determinant wave functions constructed from Hartree-Fock and, in particular, from Kohn-Sham orbitals within the collinear approach to electron spin. The scalar total spin operators S2 and Sz are partitioned by projection operators, as introduced by Clark and Davidson, in order to obtain local spin operators SASB and SzA, respectively. To complement the work of Davidson and co-workers, we analyze some features of local spins which have not yet been discussed in sufficient depth. The dependence of local spin on the choice of basis set, density functional, and projector is studied. We also discuss the results of Sz partitioning and show that SzA values depend less on these parameters than SASB values. Furthermore, we demonstrate that for small organic test molecules, a partitioning of Sz with preorthogonalized Lowdin projectors yields nearly the same results as one obtains using atoms-in-molecules projectors. In addition, the physical significance of nonzero SASB values for closed-shell molecules is investigated. It is shown that due to this problem, SASB values are useful for calculations of relative spin values, but not for absolute local spins, where SzA values appear to be better suited.     

Dehydration of Alkanones by Bare FeO+ Involves the ω/(ω − 1) Positions: Exclusion of Iron Carbenes as Intermediates. Preliminary Communication

Fourier-transform ion-cyclotron-resonance (FTICR) mass spectrometry has been used to uncover the mechanisms by which FeO⁺ dehydrates heptan-4-one ( 5a ) and nonan-5-one ( 6a ) in the gas phase. The study of isotopomeric ketones provides evidence that H₂O loss is not due to a 1,1-elimination, thus ruling out the intermediacy of high-valent iron-carbene species. Rather, H₂O is generated in a formal 1,2-elimination involving the ω/ω ? 1 positions of the alkyl chain (‘remote C? H bond activation’). In the consecutive alkene/H₂O elimination, the olefins (ethylene from 5a and propene from 6a ) originate from the terminal part of one alkyl chain, and the H-atom is transferred to the FeO⁺ moiety in the course of this process, builds up together with an H-atom from the ω/ω-1 position of the other alkyl chain the H₂O molecule. In either case, the O-atom of H₂O is provided by the FeO⁺ species.