2,746 research outputs found

    Strategic environmental assessment implementation of transport and mobility plans. The case of italian regions and provinces

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    Transport and mobility plans imply strategies and actions that affect the environment. The European Union has introduced in 2001 the strategic environmental assessment (SEA) to take into account and mitigate adverse environmental effects in planning and decision-making. SEA limited implementation has attracted the interest of many scholars that have sought methods able to assess the quality of SEA processes by identifying vices and virtues in practice. In this paper, we measure the quality of eight SEAs for transport and mobility plans of regional and provincial administrations of Italy. Results show that the overall quality level of SEA reports is only barely sufficient, Abruzzo is among the virtuous and Piedmont among the critical administrations. We also stress that the determination of impact significance has received the worse quality score. We finally compare our results to other Italian and British homologous cases finding interesting and generally confirmative evidence

    Cyclization of Cyclopropyl Carbonyls and the Homo-Nazarov Reaction

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    Ring strain confers to the cyclopropane ring an exceptional reactivity. Nevertheless, activation of the cyclopropane ring is usually needed to allow ring-opening reactions under mild conditions. The introduction of one or several carbonyl functionalities on cyclopropanes is often used to enhance their electrophilic reactivity. When a donor group is also present at the vicinal position to the carbonyl, more reactive donor-acceptor systems are obtained, which are ideally suited for homo-conjugate addition or cycloaddition reactions. This short review focuses on the special case of intramolecular cyclization reactions. Particular emphasis is devoted to the cyclization of vinyl- and aryl- cyclopropyl ketones for the formation of 6 membered rings. This process corresponds to a formal homo-Nazarov cyclization and has been only used rarely in the past. Recently, the scope of the reaction was greatly expanded by the use of a silyl group as cation stabilizing group and by the first catalytic method for the synthesis of vinyl-cyclopropyl ketones. With these new developments, the bases are now set for the application of this special class of cationic cyclizations in the synthesis of more complex synthetic and natural products

    Cyclization of Aminocyclopropanes in Indole Alkaloids Synthesis

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    The regioselective and diastereoselective cyclization of acyliminium intermediates generated from aminocyclopropanes on unprotected indoles is presented. The recent results obtained in our group are compared with previous intermolecular reactions with aminocyclopropanes as well as with other cyclization methods involving iminium ions and unprotected indoles. A first speculative analysis of possible reaction mechanisms allows rationalizing the observed selectivity. The high potential of the method for the synthesis of natural alkaloids is demonstrated in the formal synthesis of aspidospermidine and the total synthesis of goniomitine

    Indole Alkaloids Synthesis via a Selective Cyclization of Aminocyclopropanes

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    The continuous progress in medicinal chemistry requires more versatile synthetic strategies for the generation of large libraries of active compounds and their analogues. As a result, the research for new effective cyclization and cycloaddition reactions is an essential task in organic chemistry. In 2008 we developed the first catalytic formal homo-Nazarov reaction starting from activated cyclopropanes. Herein we report the extension of the catalytic formal homo-Nazarov cyclization to aminocyclopropanes. Highly diastereoselective cyclizations were obtained via an acyliminium intermediate generated through opening of the cyclopropane. An excellent control over the regioselectivity of either the C-C or C-N cyclization in the case of free indoles as nucleophilic partners was achieved. The utility of the developed methodology was demonstrated by the generation of the polycyclic scaffolds of Aspidosperma and Gonioma natural products starting from a common intermediate. Based on this method, a formal total synthesis of the alkaloid aspidospermidine and the total synthesis of the alkaloid goniomitine are presented. Finally, the scope and limitations of our methodology are discussed on an extended range of vinyl-cyclopropyl ketones with cyclic or acyclic carbamates, as well as ethers as donor groups on the cyclopropane

    Cyclization and Cycloaddition Reactions of Cyclopropyl Carbonyls and Imines

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    Abstract: Activated cyclopropanes, such as vinyl and carbonyl cyclopropanes, are useful building blocks in organic chemistry due to their exceptional reactivity. This review focuses on the use of cyclopropyl carbonyls and imines in cyclization and cycloaddition reactions for the synthesis of cyclic compounds. Cycloisomerization and other cyclization reactions are treated first, followed by formal cycloaddition reactions and applications in total synthesis. For each class of reactions, key pioneering works are shortly presented and emphasis is then set on recent results. Indeed, the utility of activated cyclopropanes in organic synthesis have been significantly increased in the last years by combining modern catalytic methods with the well-established reactivity of these building blocks. Together with progress in the synthesis of the cyclopropanes, these new methods allowed a better control over the diastereoselectivity and enantioselectivity of the reactions as well as their use for the synthesis of complex natural products

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    Advanced-Metastatic Non-Small-Cell Lung Cancer EGFR-mutated in Italy: patient management costs and potential productivity losses:

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    Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are established therapies for previously untreated advanced/metastatic non-small cell lung cancer (NSCLC) EGFR-mutated patients. Osimertinib, a third-generation TKI, has recently received the same first-line indication. This study aims at investigating management costs and potential productivity losses in Italy in this patient setting, given all the available therapeutic options. Two analyses were performed. The first evaluates first-line yearly management costs and potential productivity losses per patient, for each first-line treatment. The second, performed nationally and regionally, models all lines of treatments and costs over a five-year period, through different market-share scenarios – considering osimertinib adoption as new therapy in 60% of patients as the most probable one – and line-switch/mortality probabilities. Using this model, patients' total months of treatment and development/progression of brain metastases were also analyzed. The first analysis shows that first-line management costs and potential productivity losses are minimized by osimertinib (first-line yearly expenditure of €25.942, 8%-12% less than TKIs). The second analysis, based on a five-year horizon and on all therapy lines, shows that total management costs and potential productivity losses decrease by increasing the adoption of osimertinib as a first-line therapy (€7.4m cumulative lower cost with osimertinib at 60% compared to 0%). Considering the average month of therapy, where results are not affected by the length of the therapy, with osimertinib at 60% on naïve patients, monthly management costs and productivity losses are 10% lower than in the non-osimertinib scenario. In advanced, metastatic EGFR-mutated NSCLC, the use of osimertinib as the first-line treatment could reduce patient management costs and potential productivity losses

    Catalytic Formal Homo-Nazarov Cyclization

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    The first catalytic method for the cyclization of vinyl-cyclopropyl ketones (formal homo-Nazarov reaction) is reported. Starting from activated cyclopropanes, heterocyclic and carbocyclic compounds were obtained under mild conditions using Brønsted acid catalysts. Preliminary investigation of the reaction mechanism indicated a stepwise process

    An iterative guidance and navigation algorithm for orbit rendezvous of cooperating cubeSats

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    Modern space missions often require satellites to perform guidance, navigation, and control tasks autonomously. Despite their limited resources, small satellites are also involved in this trend, as in-orbit rendezvous and docking maneuvers and formation flying have become common requirements in their operational scenarios. A critical aspect of these tasks is that these algorithms are very much intertwined with each other, although they are often designed completely independently of one another. This paper describes the design and simulation of a guidance and relative navigation architecture for the rendezvous of two cooperating CubeSats. The integration of the two algorithms provides robustness to the solution, by simulating realistic levels of noise and uncertainty in the guidance law implementation. The proposed guidance law is derived based on the linearized equations of orbital motion, written in terms of spherical coordinates. The trajectory is iteratively corrected at a fixed time step, so that errors from the navigation and the initial orbital condition can be recovered. The navigation algorithm processes the bearing and range measurements from a camera and an intersatellite link through an unscented filter to provide the information required from the guidance law. A Monte Carlo campaign based on a 3-DOF simulation demonstrates the effectiveness of the proposed solution.</jats:p
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