Synthesis of Anellated Pyranose Derivatives on the Basis of Levoglucosenone

ABSTRACT

1,6-Anhydro-2-(dicyanomethylene)-2,3-dideoxy-4-S-ethyl-4-thio-β-D-erythro-hexopyranose (1) reacted with tosyl azide or sulfur and triethylamine to furnish the 5-aza-10, 11-dioxatricyclo[6.2.1.0^2,6]undeca-2(6),3-diene-3-carbonitrile 2 and the 10,11-dioxa-5-thiatricyclo[6.2.1.0^2,6]undeca-2(6),3-diene-3-carbonitrile 3, respectively. The reactions of 1 with arylisothiocyanates furnished the 11,12-dioxa-5-thiatricyclo[7.2.1.0^2,7]dodeca-2(7),3-diene-3-carbonitriles 4 and 5. 3 underwent cyclization with triethyl orthoformate and ammonia or hydrazine hydrate to afford the 5,7-diaza-14,15-dioxa-9-thiatetracyclo[10.2.1.0^2,10.0^3.8]pentadecatetra(tri)enes 7 and 8, respectively.     

Hiv-1 Specific Reverse Transcriptase Inhibitors: why are Tsao-Nucleosides so Unique?

1. INTRODUCTION

AIDS will still be one of the most important challenges for the Scientific Community in the approaching new century. Since the identification, in 1983-84,^1,2 of human immunodeficiency virus (HIV) as the etiological agent of AIDS, significant progress has been made in the treatment of HIV-infected patients. This has been in part due to the discovery and clinical use of an increasing number of anti-HIV drugs. However, while highly active antiretroviral therapy (HAART)³ approaches have reduced the morbidity and mortality, the intertwined problems of drug induced viral resistance, poor compliance with complex regimens and therapy failure continue. Therefore, there remains a pressing need for the development of new antiviral agents that can be used not only as first line therapeutic candidates, but also in the antiretroviral-experienced patient population.     

Transmission of HIV in sexual networks in sub-Saharan Africa and Europe

We are reviewing the literature regarding sexual networks and HIV transmission in sub-Saharan Africa and Europe. On Likoma Island in Malawi, a sexual network was reconstructed using a sociometric survey in which individuals named their sexual partners. The sexual network identified one giant component including half of all sexually active individuals. More than 25% of respondents were linked through independent chains of sexual relations. HIV was more common in the sparser regions of the network due to over-representation of groups with higher HIV prevalence. A study from KwaZulu-Natal in South-Africa collected egocentric data about sexual partners and found that new infections in women in a particular area was associated with the number of life-time partners in men. Data about sexual networks and HIV transmission are not reported in Europe. It is, however, found that the annual number of sexual partners follows a scale-free network. Phylogenetic studies that determine genetic relatedness between HIV isolates obtained from infected individuals, found that patients in the early stages of infections explain a high number of new infections. In conclusion, the limited information that is available suggest that sexual networks play a role in spread of HIV. Obtaining more information about sexual networks can be of benefit for modeling studies on HIV transmission and prevention.     

A theoretical NMR study of the structure of benzynes and some of their carbocyclic and heterocyclic analogs

This work reports the theoretical study of the aromaticity of a series of carbocycles (benzene, cyclohexane, bent and planar cyclooctatetraene) and heterocycles (pyridine, furan, thiophene, pyrrole) and their didehydro forms (arynes and hetarynes). As aromaticity probe Schleyer's NICS were used and represented in two 3D isosurfaces of the electron density. The spatial 3D representation of the NICS is shown to be a powerful tool to visualize the aromaticity (or its absence) of different molecules.     

Directed ortho-lithiation of unprotected diphenylphosphinic acids

Directed ortho lithiation of diphenylphosphinic acid and subsequent electrophilic trapping provides mono ortho-functionalized derivatives including enantiopure γ-aminophosphinic acids in moderate yields. Copper catalyzed coupling of the ortho anion leads to biphenyl-2,2′-diylbis(phenylphosphinic acid), a phosphorus analogue of biphenyl-2,2′-dicarboxylic acid. Preliminary studies of the metal-binding abilities of this O,O-chelating ligand towards a series of metal cations are included.     

Multiple Keys for a Single Lock: The Unusual Structural Plasticity of the Nucleotidyltransferase (4′)/Kanamycin Complex

The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme‐catalysed chemical modification of the drug. Over the last two decades, significant efforts in medicinal chemistry have been focused on the design of non‐ inactivable antibiotics. Unfortunately, this strategy has met with limited success on account of the remarkably wide substrate specificity of aminoglycoside‐modifying enzymes. To understand the mechanisms behind substrate promiscuity, we have performed a comprehensive experimental and theoretical analysis of the molecular‐recognition processes that lead to antibiotic inactivation by Staphylococcus aureus nucleotidyltransferase 4′(ANT(4′)), a clinically relevant protein. According to our results, the ability of this enzyme to inactivate structurally diverse polycationic molecules relies on three specific features of the catalytic region. First, the dominant role of electrostatics in aminoglycoside recognition, in combination with the significant extension of the enzyme anionic regions, confers to the protein/antibiotic complex a highly dynamic character. The motion deduced for the bound antibiotic seem to be essential for the enzyme action and probably provide a mechanism to explore alternative drug inactivation modes. Second, the nucleotide recognition is exclusively mediated by the inorganic fragment. In fact, even inorganic triphosphate can be employed as a substrate. Third, ANT(4′) seems to be equipped with a duplicated basic catalyst that is able to promote drug inactivation through different reactive geometries. This particular combination of features explains the enzyme versatility and renders the design of non‐inactivable derivatives a challenging task.     

A general and systematic framework for the kinematic analysis of complex gear systems

It is presented an integral approach for the velocity analysis of complex gear systems. Due to the intrinsic nature of the method, it can be systematically applied for gear trains with arbitrary architecture, including bevel gears with non-parallel motion axes. As a result, not only velocity ratios can be computed, but also angular velocities of any body composing the gear system. Several application examples are presented to prove the feasibility and the validity of the proposed method.     

Simple Method for the Preparation of 1,3-Dithiol-2-one and 1,3-Dithiol-2-thione

Abstract

The reaction of diisopropyl xanthogen and thio-diisopropyl xanthogen disulfide with alkynes furnished 1,3-dithiol-2-one and 1,3-dithiol-2-thione.     

Novel Copolymer of Diisopropyl Fumarate and Benzyl Acrylate Synthesized Under Microwave Energy and Quasielastic Light Scattering Measurements

Microwave assisted free radical copolymerization of diisopropyl fumarate (DIPF) and benzyl acrylate (BzA) with different copolymer compositions was performed using benzoyl peroxide as initiator. The effect of the reaction conditions on the macromolecular characteristics, monomer reactivity ratio and copolymer properties were studied. The monomer conversion and average molecular weights increase with the content of BzA units in the copolymer. The copolymers were characterized by IR, ¹H and ¹³C-NMR spectroscopies and the molecular weights were analyzed with size exclusion chromatography (SEC). The reactivity ratios obtained from an extended Kelen-Tüdös method under microwave irradiations are a factor which is double than those obtained by thermal copolymerization. The product r₁r₂ = 0.152 suggests a preference of both propagating macroradicals toward consecutive homopolymerization. The hydrodynamic and polydispersity size were measured in ethylacetate, tetrahydrofuran and methylethylketone with a quasi-elastic light scattering (QELS) technique showing that the quality of the solvents increases in the order: EA < THF < MEK.     

Size-Exclusion Chromatography of Asphaltenes: An Experimental Comparison of Commonly Used Approaches

Asphaltenes, the heaviest and most polar fraction of crude oil, are responsible for the clogging of oil pipelines and of underground reservoir rocks. Asphaltenes are defined as a solubility class (toluene- or benzene-soluble, n-alkane insoluble), and a consensus is still lacking on the molar mass (M) averages, distribution, and range of these materials. Size-exclusion chromatography (SEC) is among the most widely employed methods for characterizing the M averages and distributions of both natural and synthetic polymers and, as such, has seen widespread application in the study of asphaltenes. SEC analysis of asphaltenes presents a number of challenges, however, some inherent to all low-M materials and some unique to these particular analytes. Here, we have experimentally compared several of the most commonly used approaches to SEC of asphaltenes, in hope of both demonstrating the influence of experimental conditions upon the results obtained as well as to determine optimal conditions of analysis. In the end, while the former goal was met, the latter one remains an open challenge in the field.