Синтез нових спіроциклічних N-арилзаміщених 2-тіопіримідин-4,6-діонів

A convenient and efficient method for the synthesis of new unsaturated spiro-annulated N-aryl-4,6-dioxopyrimidine-2-thione derivatives has been developed. The resulting compounds can be potential biological active molecules or precursors for further chemical modification.Aim. To develop the methods for the synthesis of new unsaturated spiro-annulated 2-thiopyrimidine-4,6-dione derivatives, which can be used as potentially biological active molecules or precursors for their formation.Results and discussion. By condensation of N-aryl-substituted thioureas and allylmalonic acid using acetic anhydride or acetyl chloride the series of 5-allyl-substituted 2-thiopyrimidinediones has been synthesized. Their further alkylation with allyl bromide or metallyl chloride led to formation of 5,5-dialkenyl derivatives, which were converted to the corresponding unsaturated spirocyclic dioxopyrimidine-2-thiones by ring-closing metathesis. Experimental part. The synthesis of the starting compounds and title products was performed by preparative chemical methods, TLC and column chromatography, elemental analysis, NMR-spectroscopy.Conclusions. The efficient three-step synthetic route of new unsaturated spiro-annulated N-aryl-4,6-dioxopyrimidine-2-thione derivatives from the starting N-arylsubstituted thioureas and allylmalonic acid has been developed. The spiro-annulated products obtained can find application in biological and pharmaceutical science or as starting substrates for further chemical modification.Разработан удобный и эффективный метод синтеза новых ненасыщенных спиро-аннелированных N-арилзамещенных 2-тиопиримидин-4,6-дионов. Полученные соединения могут быть потенциальными биоактивными молекулами или исходными веществами для дальнейшей химической модификации.Цель работы – разработка методов получения новых ненасыщенных спиро-аннелированных производных 2-тиопиримидин-4,6-диона как потенциальных биологически активных соединений или полупродуктов для их получения.Результаты и их обсуждение. Конденсацией N-арилзамещенных тиомочевин и аллилмалоновой кислоты с использованием уксусного ангидрида или ацетилхлорида синтезирован ряд 5-аллилзамещенных 2-тиопиримидиндионов. При их последующем алкилировании аллилбромидом или металлилхлоридом получены 5,5-диалкенильные производные, которые реакциями метатезиса с закрытием цикла были конвертированы в соответствующие непредельные спироциклические диоксопиримидин-2-тионы.   Экспериментальная часть. Синтез исходных соединений и целевых продуктов классическими методами препаративной химии; очистка и идентификация полученных соединений проводились методами тонкослойной и колоночной хроматографии, методом элементного анализа, спектроскопией ЯМР.Выводы. Разработан эффективный трехстадийный путь получения из исходных тиомочевин и аллилмалоновой кислоты новых ненасыщенных спиро-аннелированных производных N-арил-4,6-диоксопиримидин-2-тиона. Полученные спироциклические продукты могут найти применение в биологии и фармацевтической науке, а также использоваться как исходные соединения для дальнейшей химической модификации.Розроблено зручний та ефективний метод синтезу нових ненасичених спіро-анельованих N-арилзаміщених 2-тіопіримідин-4,6-діонів. Одержані сполуки можуть бути потенційними біоактивними молекулами або прекурсорами для подальшої хімічної модифікації. Мета роботи – розробка методів одержання нових ненасичених спіро-анельованих похідних 2-тіопіримідин-4,6-діону як потенційних біологічно активних сполук або напівпродуктів для їх отримання. Результати та їх обговорення. КонденсацієюN-арилзаміщених тіосечовин та алілмалонової кислоти із застосуванням оцтового ангідриду або ацетилхлориду синтезовано серію 5-алілзаміщених 2-тіопіримідиндіонів. При подальшому їх алкілуванні алілбромідом або металілхлоридом одержано 5,5-діалкенільні похідні, які реакціями метатезису із закриттям циклу було перетворено на відповідні ненасичені спіроциклічні діоксопіримідин-2-тіони.Експериментальна частина. Синтез вихідних сполук та цільових продуктів класичними методами препаративної хімії; очистку та ідентифікацію отриманих сполук здійснено методами тонкошарової та колонкової хроматографії, елементним аналізом, ЯМР-спектроскопією.Висновки. Розроблено ефективний тристадійний шлях отримання з вихідних тіосечовин та алілмалонової кислоти нових ненасичених спіро-анельованих похідних N-арил-4,6-діоксопіримідин-2-тіону. Одержані спіроциклічні продукти можуть знайти застосування в біології та фармацевтичній науці, або використовуватись як вихідні сполуки для подальшої хімічної модифікації

Retrotransposon activation contributes to neurodegeneration in a Drosophila TDP-43 model of ALS

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases, but the cascade of events leading to cell death are not understood. We have expressed human TDP-43 (hTDP-43) in Drosophila neurons and glia, a model that recapitulates many of the characteristics of TDP-43-linked human disease including protein aggregation pathology, locomotor impairment, and premature death. We report that such expression of hTDP-43 impairs small interfering RNA (siRNA) silencing, which is the major post-transcriptional mechanism of retrotransposable element (RTE) control in somatic tissue. This is accompanied by de-repression of a panel of both LINE and LTR families of RTEs, with somewhat different elements being active in response to hTDP-43 expression in glia versus neurons. hTDP-43 expression in glia causes an early and severe loss of control of a specific RTE, the endogenous retrovirus (ERV) gypsy. We demonstrate that gypsy causes the degenerative phenotypes in these flies because we are able to rescue the toxicity of glial hTDP-43 either by genetically blocking expression of this RTE or by pharmacologically inhibiting RTE reverse transcriptase activity. Moreover, we provide evidence that activation of DNA damage-mediated programmed cell death underlies both neuronal and glial hTDP-43 toxicity, consistent with RTE-mediated effects in both cell types. Our findings suggest a novel mechanism in which RTE activity contributes to neurodegeneration in TDP-43-mediated diseases such as ALS and FTLD

Feasibility of a Small, Rapid Optical-to-IR Response, Next Generation Gamma Ray Burst Mission

We present motivations for and study feasibility of a small, rapid optical to IR response gamma ray burst (GRB) space observatory. By analyzing existing GRB data, we give realistic detection rates for X-ray and optical/IR instruments of modest size under actual flight conditions. Given new capabilities of fast optical/IR response (about 1 s to target) and simultaneous multi-band imaging, such an observatory can have a reasonable event rate, likely leading to new science. Requiring a Swift-like orbit, duty cycle, and observing constraints, a Swift-BAT scaled down to 190 square cm of detector area would still detect and locate about 27 GRB per yr. for a trigger threshold of 6.5 sigma. About 23 percent of X-ray located GRB would be detected optically for a 10 cm diameter instrument (about 6 per yr. for the 6.5 sigma X-ray trigger).Comment: Elaborated text version of a poster presented at 2012 Malaga/Marbella symposiu

Loss of Pi-Junction Behaviour in an Interacting Impurity Josephson Junction

Using a generalization of the non-crossing approximation which incorporates Andreev reflection, we study the properties of an infinite-U Anderson impurity coupled to two superconducting leads. In the regime where $\Delta$ and $T_K$ are comparable, we find that the position of the sub-gap resonance in the impurity spectral function develops a strong anomalous phase dependence-- its energy is a minimum when the phase difference between the superconductors is equal to $\pi$. Calculating the Josephson current through the impurity, we find that $\pi$-junction behaviour is lost as the position of the bound-state moves above the Fermi energy.Comment: 4 pages, 4 figures; labelling of Fig. 3 corrected; final published form, only trivial change

Quantum Melting and Absence of Bose-Einstein Condensation in Two-Dimensional Vortex Matter

We demonstrate that quantum fluctuations suppress Bose-Einstein condensation of quasi-two-dimensional bosons in a rapidly-rotating trap. Our conclusions rest in part on an effective-Lagrangian description of the triangular vortex lattice, and in part on microscopic Bogoliubov equations in the rapid-rotation limit. We obtain analytic expressions for the collective-excitation dispersion, which, in a rotating system, is quadratic rather than linear. Our estimates for the boson filling factor at which the vortex lattice melts at zero temperature due to quantum fluctuations are consistent with recent exact-diagonalization calculations.Comment: 4 pages, 1 figures, version to appear in Phys. Rev. Let

Quantum Phases of Vortices in Rotating Bose-Einstein Condensates

We investigate the groundstates of weakly interacting bosons in a rotating trap as a function of the number of bosons, $N$, and the average number of vortices, $N_V$. We identify the filling fraction $\nu\equiv N/N_V$ as the parameter controlling the nature of these states. We present results indicating that, as a function of $\nu$, there is a zero temperature {\it phase transition} between a triangular vortex lattice phase, and strongly-correlated vortex liquid phases. The vortex liquid phases appear to be the Read-Rezayi parafermion states

Simple Bosonization Solution of the 2-channel Kondo Model: I. Analytical Calculation of Finite-Size Crossover Spectrum

We present in detail a simple, exact solution of the anisotropic 2-channel Kondo (2CK) model at its Toulouse point. We reduce the model to a quadratic resonant-level model by generalizing the bosonization-refermionization approach of Emery and Kivelson to finite system size, but improve their method in two ways: firstly, we construct all boson fields and Klein factors explicitly in terms of the model's original fermion operators $c_{k \sigma j}$, and secondly we clarify explicitly how the Klein factors needed when refermionizing act on the original Fock space. This enables us to explicitly follow the adiabatic evolution of the 2CK model's free-fermion states to its exact eigenstates, found by simply diagonalizing the resonant-level model for arbitrary magnetic fields and spin-flip coupling strengths. In this way we obtain an {\em analytic} description of the cross-over from the free to the non-Fermi-liquid fixed point. At the latter, it is remarkably simple to recover the conformal field theory results for the finite-size spectrum (implying a direct proof of Affleck and Ludwig's fusion hypothesis). By analyzing the finite-size spectrum, we directly obtain the operator content of the 2CK fixed point and the dimension of various relevant and irrelevant perturbations. Our method can easily be generalized to include various symmetry-breaking perturbations. Furthermore it establishes instructive connections between different renormalization group schemes such as poor man's scaling, Anderson-Yuval type scaling, the numerical renormalization group and finite-size scaling.Comment: 35 pages Revtex, 7 figures, submitted to Phys. Rev.

Pairing Symmetry Competition in Organic Superconductors

A review is given on theoretical studies concerning the pairing symmetry in organic superconductors. In particular, we focus on (TMTSF)$_2$X and $\kappa$-(BEDT-TTF)$_2$X, in which the pairing symmetry has been extensively studied both experimentally and theoretically. Possibilities of various pairing symmetry candidates and their possible microscopic origin are discussed. Also some tests for determining the actual pairing symmtery are surveyed.Comment: 16 pages, 8 figures, to be published in J. Phys. Soc. Jpn., special issue on "Organic Conductors

Vortex liquids and vortex quantum Hall states in trapped rotating Bose gases

We discuss the feasibility of quantum Hall states of vortices in trapped low-density two-dimensional Bose gases with large particle interactions. For interaction strengths larger than a critical dimensionless 2D coupling constant $g_c \approx 0.6$, upon increasing the rotation frequency, the system is shown to spatially separate into vortex lattice and melted vortex lattice (vortex liquid) phases. At a first critical frequency, the lattice melts completely, and strongly correlated vortex and particle quantum Hall liquids coexist in inner respectively outer regions of the gas cloud. Finally, at a second critical frequency, the vortex liquid disappears and the strongly correlated particle quantum Hall state fills the whole sample.Comment: 11 pages, 3 figures; to appear in J. Phys.

Thermal conductivity via magnetic excitations in spin-chain materials

We discuss the recent progress and the current status of experimental investigations of spin-mediated energy transport in spin-chain and spin-ladder materials with antiferromagnetic coupling. We briefly outline the central results of theoretical studies on the subject but focus mainly on recent experimental results that were obtained on materials which may be regarded as adequate physical realizations of the idealized theoretical model systems. Some open questions and unsettled issues are also addressed.Comment: 17 pages, 4 figure