Formal Total Synthesis of the Algal Toxin (−)-Polycavernoside A

A concise and largely catalysis-based approach to the potent algal toxin polycavernoside A (1) is described that intercepts a late-stage intermediate of a previous total synthesis; from there on, this challenging target can be reached in a small number of steps. Key to success was a sequence of a molybdenum-catalyzed ring-closing alkyne metathesis (RCAM) reaction to forge the macrocyclic frame, followed by a gold-catalyzed and strictly regioselective transannular hydroalkoxylation of the resulting cycloalkyne that allows the intricate oxygenation pattern of the macrolactone ring of 1 to be properly set. The required cyclization precursor 5 was assembled by the arguably most advanced fragment coupling process based on an Evans–Tishchenko redox esterification known to date, which was optimized to the extent that the precious coupling partners could be used in an almost equimolar ratio (6/7 1:1.3). The preparation of these building blocks features, inter alia, the power of the Sc(OTf)3-catalyzed Leighton crotylation as well as the superb selectivities of alkene cross metathesis, asymmetric keto-ester hydrogenation, and the Jacobsen epoxidation/epoxide resolution technologies

Total Syntheses and Biological Reassessment of Lactimidomycin, Isomigrastatin and Congener Glutarimide Antibiotics

Lactimidomycin (1) was described in the literature as an exquisitely potent cell migration inhibitor. Encouraged by this claim, we developed a concise and scalable synthesis of this bipartite glutarimide-macrolide antibiotic, which relies on the power of ring-closing alkyne metathesis (RCAM) for the formation of the unusually strained 12-membered head group. Subsequent deliberate digression from the successful path to 1 also brought the sister compound isomigrastatin (2) as well as a series of non-natural analogues of these macrolides into reach. A careful biological re-evaluation of this compound collection showed 1 and progeny to be potently cytotoxic against a panel of cancer cell lines, even after one day of compound exposure; therefore any potentially specific effects on tumor cell migration were indistinguishable from the acute effect of cell death. No significant cell migration inhibition was observed at sub-toxic doses. Although these findings cannot be reconciled with some reports in the literature, they are in accord with the notion that lactimidomycin is primarily a ribosome-binder able to effectively halt protein biosynthesis at the translation stage

Increasing the Structural Span of Alkyne Metathesis

A new generation of alkyne metathesis catalysts, which are distinguished by high activity and an exquisite functional group tolerance, allows the scope of this transformation to be extended beyond its traditional range. They accept substrates that were previously found problematic or unreactive, such as propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of various types, and even terminal alkynes. Moreover, post-metathetic transformations other than semi-reduction increase the structural portfolio, as witnessed by the synthesis of a annulated phenol derivative via ring-closing alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene reaction. Further examples encompass a post-metathetic transannular ketone–alkyne cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox isomerization, and a Meyer–Schuster rearrangement/oxa-Michael cascade. These reaction modes fueled model studies toward salicylate macrolides, furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A; moreover, they served as the key design elements of concise total syntheses of dehydrocurvularin (27) and the antibiotic agent A26771B (36)

3 Cat-4 mission, 1-Unit CubeSat for earth observation: Evaluation on the qualification and production during Phase D

The 3Cat-4 mission is a 1-unit CubeSat platform that serves as a technology demonstrator and educational platform for students at Universitat Politècnica de Catalunya (UPC). Promoted by the UPC Nanosatellite and Payload Laboratory (UPC NanoSatLab), the most notable subsystems that innovate in the nanosatellite scenario are (1) the Flexible Microwave Payload - 1 (FMPL-1) [1], a cost-effective payload to execute Global Navigation Satellite System Reflectometry (GNSS-R), and L-band microwave radiometry experiments using a commercial off-the-shelf (COTS) software-defined radio (SDR) and (2) the Nadir Antenna Deployment Subsystem (NADS) [2], an in-orbit deployable high-directivity antenna used by Earth Observation (EO) payloads. This paper presents the findings of the 3Cat-4 mission during Phase D, the qualification and production phase of the project. Since the publication of the first introductory work for this mission in 2019[3], several sections of the subsystems have been redesigned and upgraded to correct previous design flaws or to meet new requirements. In addition, this paper addresses the educational perspective of this mission, analyzing its performance and usefulness in the aforementioned subject

Preparation of anti-vicinal amino alcohols: asymmetric synthesis of D-erythro-Sphinganine, (+)-spisulosine and D-ribo-phytosphingosine

Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM-ether directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, while the Overman rearrangement of chiral allylic trichloroacetimidates generated by asymmetric reduction of an alpha,beta-unsaturated methyl ketone allowed rapid access to both D-ribo-phytosphingosine and L-arabino-phytosphingosine

Mission and system architecture for an operational network of earth observation satellite nodes

Nowadays, constellations and distributed networks of satellites are emerging as clear development trends in the space system market to enable augmentation, enhancement, and possibilities of new applications for future Earth Observation (EO) missions. While the adoption of these satellite architectures is gaining momentum for the attaining of ever more stringent application requirements and stakeholder needs, the efforts to analyze their benefits and suitability, and to assess their impact for future programmes remains as an open challenge to the EO community. In this context, this paper presents the mission and system architecture conceived during the Horizon 2020 ONION project, a European Union research activity that proposes a systematic approach to the optimization of EO space infrastructures. In particular, ONION addressed the design of complementary assets that progressively supplement current programs and took part in the exploration of needs and implementation of architectures for the Copernicus Space Component for EO. Among several use cases considered, the ONION project focused on proposing system architectures to provide improved revisit time, data latency and image resolution for a demanding application scenario of interest: Marine Weather Forecast (MWF). A set of promising system architectures has been subject of a comprehensive assessment, based on mission analysis expertise and detailed simulation for evaluating several key parameters such as revisit time and data latency of each measurement of interest, on-board memory evolution and power budget of each satellite of the constellation, ground station contacts and inter-satellite links. The architectures are built with several heterogeneous satellite nodes distributed in different orbital planes. Each platform can embark different instrument sets, which provide the required measurements for each use case. A detailed mission analysis has then been performed to the selected architecture for the MWF use case, including a refined data flow analysis to optimize system resources; a refined power budget analysis; a delta-V and a fuel budget analysis considering all the possible phases of the mission. This includes from the correction of launcher injection errors and acquisition of nominal satellite position inside the constellation, orbit maintenance to control altitude, collision avoidance to avoid collision with space debris objects and end-of-life (EOL) disposal to comply with EOL guidelines. The relevance of the system architecture selected for the MWF has been evaluated for three use cases of interest (Arctic sea-ice monitoring, maritime fishery pressure and aquaculture, agricultural hydric stress) to show the versatility and the feasibility of the chosen architecture to be adapted for other EO applications.This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 687490

Target 2035 - an update on private sector contributions

Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging ‘open’ principles to develop a pharmacological tool for every human protein. These tools are important reagents for scientists studying human health and disease and will facilitate the development of new medicines. It is therefore not surprising that pharmaceutical companies are joining Target 2035, contributing both knowledge and reagents to study novel proteins. Here, we present a brief progress update on Target 2035 and highlight some of industry's contributions

Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review

Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied

Interrelación de laboratorios de control y laboratorios de investigación en España para la armonización de metodologías de determinación de toxinas paralizantes

XII Congreso Nacional de Agricultura, Madrid 24-26 de noviembre de 2009Marketing of cultured and harvested shellfish is linked to monitoring programs for granting food safety. Its complexity requires constant cooperation between research and monitoring laboratories in order to improve sampling and analysing performances, achieve legal requirements, etc. for increasing consumer’s health protection but not reducing producer’s benefits. The JACUMAR project «Comparison of methodologies for the evaluation of Paralytic Shellfish Poisoning (PSP) toxins in bivalves. Application for aquaculture in Spain» groups research and monitoring laboratories from Galicia, Andalucía and Cataluña. Efforts are focused on detection and quantification of PSP toxins, searching an analytical method able to fulfil technical and management requirementsEste proyecto está financiado por la Junta Asesora de Cultivos Marinos (JACUMAR), y los programas de control por los gobiernos autónomos de Galicia, Andalucía y CataluñaN

A modular, enantioselective synthesis of resolvins D3, E1, and hybrids

Resolvins D3 and E1 are important signaling molecules in the resolution of inflammation. Here, we report a convergent and flexible strategy to prepare these natural products using Hiyama-Denmark coupling of five- and six-membered cyclic alkenylsiloxanes to connect three resolvin fragments, and control the stereochemistry of the natural product (Z)-alkenes. The modular nature of this approach enables the synthesis of novel resolvin hybrids, opening up opportunities for more-extensive investigations of resolvin biology