Enantioselective approaches to potential MetAP-2 reversible inhibitors

[reaction: see text] Enantioselective deprotonation of 4-substituted cyclohexanones and highly stereoselective conjugate addition of higher order mixed cuprates were the key steps in a concise synthesis of fumagalone-related molecules. The origin of the (low) biological activity of the new compounds as compared to fumagalone is briefly discussed.     

Towards a parameter-free characterization of charge transfer via hopping: the case of tris(8-hydroxyquinolato) aluminum

By using calculations based on density functional theory, we investigate the physical factors determining the elemental charge transfer in Alq3, taken as a prototype of molecular systems in condensed phase. The effect of the environment on the hopping of the charge carrier is evaluated self-consistently in a model in which an Alq3 dimer is embedded in an ensemble of permanent and polarizable dipoles, including orientational disorder and the presence of impurities. The results indicate that the origin of the activation barrier is mainly extrinsic and that the local orientation of the dipole moments plays a major role. The influence of nonadiabaticity is also studied and found to be more important for a hole than for an electron.     

Novel bioactive phospholipids: practical total syntheses of products from the oxidation of arachidonic and linoleic esters of 2-lysophosphatidylcholine(1)

Total syntheses of nine novel phospholipids were accomplished to facilitate the identification and biological testing of compounds that are generated upon oxidative cleavage of arachidonate and linoleate esters of 2-lysophosphatidylcholine, the two most abundant polyunsaturated phospholipids in low-density lipoprotein. An efficient general synthesis exploiting 2-lithiofuran as a 4-oxo-2-butenoyl carbanion equivalent provided phospholipids containing gamma-keto-alpha,beta-unsaturated carbonyl functional arrays. By exploiting facile cis-trans isomerizations, two commercially available cis alkenes, (2Z)-2-butene-1,4-diol and 2,5-dihydrofuran, could be employed as starting materials for preparing the Horner-Wadsworth-Emmons reagent 4-(diethoxyphosphoryl)-2E-butenal, a valuable building block for the synthesis of 2,4-dienals. The reagent was exploited in a total synthesis of 13-oxotridec-9E,11E-dienoic acid, confirming the identity of this product that is generated upon autoxidation of linoleic acid and by decomposition of 13-hydroperoxy-9,11-octadecadienoate (13-HPODE), especially in the presence of redox active transition metal ions, cytochrome p-450, or hydroperoxide lyase.     

Toward a stable apoptolidin derivative: identification of isoapoptolidin and selective deglycosylation of apoptolidin

[formula: see text] Isoapoptolidin was isolated from crude fermentation extracts of the apoptolidin-producing microorganism Nocardiopsis sp. Apoptolidin isomerizes to isoapoptolidin upon treatment with methanolic triethylamine to establish a 1.4:1 equilibrium mixture of isoapoptolidin and apoptolidin. Semisynthesis of a peracetylated and deglycosylated derivative of apoptolidin is also described.     

Near-field probing of active photonic-crystal structures

We report a study of the optical near field of an active integrated component operating near the 1.55-mum telecommunications wavelength. The device is based on a two-dimensional photonic crystal etched in a suspended InP membrane. Topographic as well as optical information is collected by use of a scanning near-field optical microscope in collection mode, providing information about the local distribution of the losses.     

Two-Dimensional Numerical Simulations of Photon Scanning Tunneling Microscopy: Fourier Modal Method and R-Matrix Algorithm

Numerical simulation of a two-dimensional probe–object system for photon scanning tunneling microscope is presented. The R-matrix propagation algorithm incorporated into the Fourier modal method was used to achieve an extended capability for modeling of a realistic system consisting of both a probe and a sample. The type of the mode guided through the dielectric probe and the coupling of the near-field to fundamental guiding mode in the probe are discussed. The influence of the probe parameters on the near-field images is investigated. Three different probe shapes were simulated in the constant height scanning mode. The transmitted flux intensity through the probe was found to be strongly dependent on the tip shape. The analysis shows a good agreement of the obtained results with the available theoretical works and confirming experimental results. The proposed numerical scheme can find applications for near-field probe characterization and provides an understanding of the degree of perturbation introduced by a probe tip in the experiment.     

Crystal and molecular structure of 1,4-diphenyl-2,3-dioxabicyclo[2,2,1] heptane,C17H16O2

The crystal structure of 1,4-diphenyl-2,3-dioxabicyclo [2,2,1] heptane has been determined from three-dimensional counter data and refined by full-matrix least-squares procedures. This endoperoxide compound crystallizes from ethanol in space groupP2₁/c with cell constantsa = 11.797(1),b = 9.051(8),c = 12.472(1) Å, = 93.78(1) °,Z = 4,D _x = 1.261, andD _m = 1.274 g cm^–3. The final residual for 2238 observed reflections is 0.063. The molecular structure possesses both an unusually long peroxide bond, 1.501(2) Å, and adjoining C-O bonds, 1.459(2) Å. This observation confirms a previously made conjecture that the forcedcis coplanarity of the C-O-O-C torsion angle would permit repulsive antisymmetric vicinal orbital interactions between the oxygen centers, destabilizing the peroxide bond relative to that normally encountered as the commonly observedgauche conformation.     

Oxidative fragmentation of hydroxy octadecadienoates generates biologically active gamma-hydroxyalkenals

Oxidative fragmentation of polyunsaturated fatty acids (PUFAs) in vivo generates cytotoxic aldehydes. Among these, 4-hydroxynon-2-enal and analogous gamma-hydroxyalkenal phosphatidylcholines (PCs) have attracted attention because these oxidatively truncated lipids are biologically active and have been implicated in diseases. A previous study showed that hydroxydienes, generated by allylic oxygenation of linoleic acid, are unreactive toward oxidative fragmentation. We now show that, in the presence of hydroperoxides, hydroxydienes fragment as readily as the corresponding hydroperoxydienes, generating gamma-hydroxyalkenals. In a physiomimetic model study, myeloperoxidase-promoted free radical-induced fragmentation of either hydroperoxy- or hydroxyoctecadienoate esters of 2-lyso-PC in small unilamellar vesicles produced the 9-hydroxy-12-oxododec-10-enoic acid (HODA) ester HODA-PC. Therefore, hydroxydienes, that are generally more abundant in vivo than hydroperoxydienes, are plausible intermediates in the production of oxidatively truncated lipids in vivo where a constant flux of radicals and hydroperoxides is present. Our findings also show that the formation of dioxetane intermediates through peroxyradical cyclization is not required to achieve oxidative fragmentation of PUFAs.     

Suppression of radiative losses of surface polaritons on nanostructured thin metal films

The strong electromagnetic coupling between surface plasmon polariton modes on opposite interfaces of a finite thickness periodically nanostructured metal film has been studied. Surface polariton dispersion and associated electromagnetic field distributions have been analyzed. It was shown that at a frequency that corresponds to the crossing of film Bloch modes of different symmetries, the radiative losses of surface polaritons that are related to the polaritons' coupling to light during propagation on the structured surface are suppressed.     

Experimental study of the BEC-BCS crossover region in lithium 6

We report Bose-Einstein condensation of weakly bound 6Li2 molecules in a crossed optical trap near a Feshbach resonance. We measure a molecule-molecule scattering length of 170(+100)(-60) nm at 770 G, in good agreement with theory. We study the 2D expansion of the cloud and show deviation from hydrodynamic behavior in the BEC-BCS crossover region.