Palladium-Catalyzed Dehydrogenative Coupling: An Efficient Synthetic Strategy for the Construction of the Quinoline Core

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C-H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners.Ministerio de Economia y Competitividad (CTQ2013-41229-P, CTQ2016-74881-P), Gobierno Vasco (IT1045-16) and Universidad del Pais Vasco/Euskal Herriko Unibertsitatea UPV/EHU are gratefully acknowledged for their financial support. V.O.-d.-E., A.C.-M. wish to thank Gobierno Vasco for grants. Technical and human support provided by Servicios Generales de Investigacion SGIker (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is also acknowledged

Pd(II)-Catalyzed Fujiwara-Moritani Reactions for the Synthesis and Functionalization of Substituted Coumarins.

[EN]Highly substituted coumarins, privileged and versatile scaffolds for bioactive natural products and fluorescence imaging, are obtained via a Pd(II)-catalyzed direct C–H alkenylation reaction (Fujiwara–Moritani reaction), which has emerged as a powerful tool for the construction and functionalization of heterocyclic compounds because of its chemical versatility and its environmental advantages. Thus, a selective 6-endo cyclization led to 4-substituted coumarins in moderate yields. Selected examples have been further functionalized in C3 through a second intermolecular C–H alkenylation reaction to give coumarin-acrylate hybrids, whose fluorescence spectra have been measured.Ministerio de Economía y Competitividad (FEDER CTQ2016-74881-P), Ministerio de Ciencia e Innovación (PID2019-104148GB-I00), and Gobierno Vasco (IT1045-16) are gratefully acknowledged for their financial support. A.C.-M. wishes to thank Gobierno Vasco for a grant. Technical and human support provided by Servicios Generales de Investigación SGIker (UPV/EHU, MINECO, GV/EJ, ERDF and ESF) is also acknowledged

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Pd(II)-Catalyzed Fujiwara-Moritani Reactions for the Synthesis and Functionalization of Substituted Coumarins

Highly substituted coumarins, privileged and versatile scaffolds for bioactive natural products and fluorescence imaging, are obtained via a Pd(II)-catalyzed direct C-H alkenylation reaction (Fujiwara-Moritani reaction), which has emerged as a powerful tool for the construction and functionalization of heterocyclic compounds because of its chemical versatility and its environmental advantages. Thus, a selective 6-endo cyclization led to 4-substituted coumarins in moderate yields. Selected examples have been further functionalized in C3 through a second intermolecular C-H alkenylation reaction to give coumarin-acrylate hybrids, whose fluorescence spectra have been measured.Ministerio de Economía y Competitividad (FEDER CTQ2016-74881-P), Ministerio de Ciencia e Innovación (PID2019-104148GB-I00), and Gobierno Vasco (IT1045-16) are gratefully acknowledged for their financial support. A.C.-M. wishes to thank Gobierno Vasco for a grant.Peer reviewe

MCDCalc: Markov Chain Molecular Descriptors Calculator for Medicinal Chemistry

[Aims] Cheminformatics models are able to predict different outputs (activity, property, chemical reactivity) in single molecules or complex molecular systems (catalyzed organic synthesis, metabolic reactions, nanoparticles, etc.).[Background] Cheminformatics models are able to predict different outputs (activity, property, chemical reactivity) in single molecules or complex molecular systems (catalyzed organic synthesis, metabolic reactions, nanoparticles, etc.).[Objective] Objective: Cheminformatics prediction of complex catalytic enantioselective reactions is a major goal in organic synthesis research and chemical industry. Markov Chain Molecular Descriptors (MCDs) have been largely used to solve Cheminformatics problems. There are different types of Markov chain descriptors such as Markov-Shannon entropies (Shk), Markov Means (Mk), Markov Moments (πk), etc. However, there are other possible MCDs that have not been used before. In addition, the calculation of MCDs is done very often using specific software not always available for general users and there is not an R library public available for the calculation of MCDs. This fact, limits the availability of MCMDbased Cheminformatics procedures.[Methods] We studied the enantiomeric excess ee(%)[Rcat] for 324 α-amidoalkylation reactions. These reactions have a complex mechanism depending on various factors. The model includes MCDs of the substrate, solvent, chiral catalyst, product along with values of time of reaction, temperature, load of catalyst, etc. We tested several Machine Learning regression algorithms. The Random Forest regression model has R2 > 0.90 in training and test. Secondly, the biological activity of 5644 compounds against colorectal cancer was studied.[Result] We developed very interesting model able to predict with Specificity and Sensitivity 70-82% the cases of preclinical assays in both training and validation series.[Conclusion] The work shows the potential of the new tool for computational studies in organic and medicinal chemistry.Spanish Ministry of Economy and Competitiveness (FEDER CTQ2016-74881-P) and (CTQ2013-41229-P) and Basque Government (IT1045-16) are gratefully acknowledged for their financial support. This work is supported by “Collaborative Project in Genomic Data Integration (CICLOGEN)” PI17/01826 funded by the Carlos III Health Institute from the Spanish National Plan for Scientific and Technical Research and Innovation 2013-2016 and the European Regional Development Funds (FEDER). This project as also supported by the General Directorate of Culture, Education and University Management of Xunta de Galicia ED431D 2017/16 and “Drug Discovery Galician Network” Ref. ED431G/01 and the “Galician Network for Colorectal Cancer Research” (Ref. ED431D 2017/23) and finally by the Spanish Ministry of Economy and Competitiveness for its support with the funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13-3503) and the European Regional Development Funds (FEDER) by the European Union.Peer reviewe