Synthesis of Seven- and Eight-Membered Rings by a Brønsted Acid Catalyzed Cationic Carbocyclization of Biphenyl Embedded Enynes.

A Brønsted acid catalyzed cyclization of o-alkenyl-o'-alkynylbiaryls for the synthesis of biologically relevant dibenzo-fused medium-sized rings has been developed. The outcome of the cyclization is determined by the nature of the substituent at the alkyne, with arenes favoring seven-membered rings and alkyl substituents producing eight-membered rings. These reactions proceed via a vinyl cation, which is captured by water and, notably, by C-nucleophiles, such as electron-rich (hetero)arenes.

Hyper-Cross-Linked Porous Polymer Featuring B-N Covalent Bonds (HCP-BNs): A Stable and Efficient Metal-Free Heterogeneous Photocatalyst.

The first example of a porous polymer containing B-N covalent bonds, prepared from a tetraphene B-N monomer and biphenyl as a comonomer, is reported. It was prepared using the solvent knitting strategy, which allows the connection between the aromatic rings of the two monomers through methylene groups provided by an external cross-linking agent. The new polymer exhibited micromeso porosity with an SBET of 612 m2/g, high thermal stability, and potential properties as a heterogeneous photocatalyst, since it is very active in the aza-Henry coupling reaction (>98% of conversion and selectivity). After the first run, the catalyst improves its photocatalytic activity, shortening the reaction time to only 2 h and maintaining this activity in successive runs. The presence of a radical in this structure that remains stable with successive runs makes it a new type of material with potential applications as a highly stable and efficient photocatalyst.

Gold(I) Catalysis Applied to the Stereoselective Synthesis of Indeno[2,1-b]thiochromene Derivatives and Seleno Analogues.

A gold(I)-catalyzed cascade reaction for the stereoselective synthesis of sulfur- or selenium-containing indeno[1,2-b]chromene derivatives from o-(alkynyl)styrenes substituted at the triple bond with a thio- or seleno-aryl group is described. The reaction involves a double cyclization process through a proposed key gold-cyclopropyl carbene intermediate that evolves by the intramolecular addition of an aromatic to the cyclopropane ring, affording polycyclic structures. The enantioselective version was studied using gold(I) complexes bearing chiral ligands.

Synthesis of BN-Polyarenes by a Mild Borylative Cyclization Cascade.

Reaction of BCl3 with suitably substituted o-alkynylanilines promotes a cascade reaction in which BN-polycyclic compounds are obtained via the formation of two new cycles and three new bonds in a single operational step. The reaction is highly efficient and takes place at room temperature, providing a very mild and straightforward strategy for the preparation of BN-aromatic compounds, which can be further transformed into a variety of BN-PAHs with different polycyclic cores and substituents.

Metal-Free Temperature-Controlled Regiodivergent Borylative Cyclizations of Enynes: BCl3 -Promoted Skeletal Rearrangement.

Metal-free borylative cyclization of biphenyl-embedded 1,3,5-trien-7-ynes in the presence of simple and inexpensive BCl3 provided synthetically useful borylated building blocks. The outcome of the process depends on the reaction temperature, with borylated phenanthrenes obtained at 60 °C and phenanthrene-fused borylated cyclobutanes formed at 0 °C. Based on DFT calculations, a mechanism for these novel transformations has been proposed, which involves an uncommon skeletal rearrangement, including migration of a methyl group and alkyne fragmentation, unprecedented in BCl3 -promoted cyclization reactions.

Mo-Catalyzed One-Pot Synthesis of N-Polyheterocycles from Nitroarenes and Glycols with Recycling of the Waste Reduction Byproduct. Substituent-Tuned Photophysical Properties.

A catalytic domino reduction-imine formation-intramolecular cyclization-oxidation for the general synthesis of a wide variety of biologically relevant N-polyheterocycles, such as quinoxaline- and quinoline-fused derivatives, and phenanthridines, is reported. A simple, easily available, and environmentally friendly dioxomolybdenum(VI) complex has proven to be a highly efficient and versatile catalyst for transforming a broad range of starting nitroarenes involving several redox processes. Not only is this a sustainable, step-economical as well as air- and moisture-tolerant method, but also it is worth highlighting that the waste byproduct generated in the first step of the sequence is recycled and incorporated in the final target molecule, improving the overall synthetic efficiency. Moreover, selected indoloquinoxalines have been photophysically characterized in cyclohexane and toluene with exceptional fluorescence quantum yields above 0.7 for the alkyl derivatives.

Selective Synthesis of Phenanthrenes and Dihydrophenanthrenes via Gold-Catalyzed Cycloisomerization of Biphenyl Embedded Trienynes.

Readily available o'-alkenyl-o-alkynylbiaryls, a particular type of 1,7-enynes, undergo a selective cycloisomerization reaction in the presence of a gold(I) catalyst to give interesting phenanthrene and dihydrophenanthrene derivatives in high yields. The solvent used provokes a switch in the evolution of the gold intermediate and plays a key role in the reaction outcome.

SARS-COV2/COVID-19 en Colombia: tendencias, predicciones y tensiones sobre el sistema sanitario / SARS-C0V2/COVID-I9 in Colombia: tendencies, predictions, and tensions about health system

RESUMEN Objetivo Analizar la evolución temporal de la primera etapa del COVID-19 en Colombia a través del modelo SIRD. Métodos Se analizó la evolución temporal del COVID-19 según los individuos infectados en Colombia del 6 de marzo al 15 de abril de 2020. Se realizó el modelo SIRD modificando la tasa de transmisión (b) bajo tres escenarios: 1) cuarentena hasta el 1 de julio, 2) cuarentena flexible., hasta el 11 de mayo con un b del 4%, y 3) cuarentena flexible2 hasta el 11 de mayo con b del 8%, con el fin de predecir el número de casos totales y el 5% de infectados en UCI para contrastarlo con el número de camas y personal UCI. Resultados Los escenarios mostraron que levantar la cuarentena el 11 de mayo significará un aumento en el número de infectados, entre 54 105 a 116 081 individuos con COVID-19. Así mismo, la rápida aceleración en la tasa de contagios se traduce en una mayor demanda de camas y personal en UCI: en el escenario de cuarentena flexible2 se colapsarían las 2 650 camas disponibles y se necesitaría de 5 intensivitas y 4 enfermeras por paciente al 1 julio. Conclusión Las medidas de distanciamiento social obligatorias contribuyen al retraso de la saturación del sistema de salud; sin embargo, son difíciles de sostener en el tiempo desde una perspectiva económica. Por lo tanto, para tener una distensión de la cuarentena es necesario adoptar medidas para ampliar la capacidad del sistema de salud y así evitar su colapso.(AU)

ABSTRACT Objective To analyze the temporal progress in the early stage of COVID-19 in Colombia using the SIRD model. Methods We analyzed the temporal progress of COVID-19 based on the number of infected persons between March 6th and April 15th, 2020. The SIRD model was implemented with variation in the rate of transmission (b) in three ways. A. Quarantine until July 11. 2. B. Flexible quarantine, [b=4%]. C. Flexible quarantine2 [b=8%]. Consecutively, we aimed to predict the number of total cases and 5% of infected persons in ICU to match them with the hospital beds and ICU staff. Results The results show that the number of COVID-19 cases will increase from 54 105 to 116 081 approximately, if the quarantine is lifted on May 11. If the infection rate increase, more hospital beds and a bigger ICU staff will be mandatory. The currently 2 650 beds won't be enough in the flexible quarantine2, and five intensive care specialist and four nurses per patient will be needed. Conclusion Measures like mandatory social distancing help delay the saturation of the health care system. However, it's impracticable to maintain them due to a possible economic crisis. Therefore, it's necessary to take action to enhance the ability of the health care system to avoid a collapse.(AU)

SARS-COV2/COVID-19 en Colombia: tendencias, predicciones y tensiones sobre el sistema sanitario / SARS-C0V2/COVID-19 in Colombia: tendencies, predictions, and tensions about health system

RESUMEN Objetivo Analizar la evolución temporal de la primera etapa del COVID-19 en Colombia a través del modelo SIRD. Métodos Se analizó la evolución temporal del COVID-19 según los individuos infectados en Colombia del 6 de marzo al 15 de abril de 2020. Se realizó el modelo SIRD modificando la tasa de transmisión (b) bajo tres escenarios: 1) cuarentena hasta el 1 de julio, 2) cuarentena flexible., hasta el 11 de mayo con un b del 4%, y 3) cuarentena flexible2 hasta el 11 de mayo con b del 8%, con el fin de predecir el número de casos totales y el 5% de infectados en UCI para contrastarlo con el número de camas y personal UCI. Resultados Los escenarios mostraron que levantar la cuarentena el 11 de mayo significará un aumento en el número de infectados, entre 54 105 a 116 081 individuos con COVID-19. Así mismo, la rápida aceleración en la tasa de contagios se traduce en una mayor demanda de camas y personal en UCI: en el escenario de cuarentena flexible2 se colapsarían las 2 650 camas disponibles y se necesitaría de 5 intensivitas y 4 enfermeras por paciente al 1 julio. Conclusión Las medidas de distanciamiento social obligatorias contribuyen al retraso de la saturación del sistema de salud; sin embargo, son difíciles de sostener en el tiempo desde una perspectiva económica. Por lo tanto, para tener una distensión de la cuarentena es necesario adoptar medidas para ampliar la capacidad del sistema de salud y así evitar su colapso.(AU)

ABSTRACT Objective To analyze the temporal progress in the early stage of COVID-19 in Colombia using the SIRD model. Methods We analyzed the temporal progress of COVID-19 based on the number of infected persons between March 6th and April 15th, 2020. The SIRD model was implemented with variation in the rate of transmission (b) in three ways. A. Quarantine until July 11. 2. B. Flexible quarantine, [b=4%]. C. Flexible quarantine2 [b=8%]. Consecutively, we aimed to predict the number of total cases and 5% of infected persons in ICU to match them with the hospital beds and ICU staff. Results The results show that the number of COVID-19 cases will increase from 54 105 to 116 081 approximately, if the quarantine is lifted on May 11. If the infection rate increase, more hospital beds and a bigger ICU staff will be mandatory. The currently 2 650 beds won't be enough in the flexible quarantine2, and five intensive care specialist and four nurses per patient will be needed. Conclusion Measures like mandatory social distancing help delay the saturation of the health care system. However, it's impracticable to maintain them due to a possible economic crisis. Therefore, it's necessary to take action to enhance the ability of the health care system to avoid a collapse.(AU)

[SARS-C0V.2/COVID-I9 in Colombia: tendencies, predictions, and tensions about health system]. / SARS-COV.2/COVID-19 en Colombia: tendencias, predicciones y tensiones sobre el sistema sanitario.

OBJECTIVE: To analyze the temporal progress in the early stage of COVID-19 in Colombia using the SIRD model. METHODS: We analyzed the temporal progress of COVID-19 based on the number of infected persons between March 6th and April 15th, 2020. The SIRD model was implemented with variation in the rate of transmission (b) in three ways. A. Quarantine until July 11. 2. B. Flexible quarantine, [b=4%]. C. Flexible quarantine2 [b=8%]. Consecutively, we aimed to predict the number of total cases and 5% of infected persons in ICU to match them with the hospital beds and ICU staff. RESULTS: The results show that the number of COVID-19 cases will increase from 54 105 to 116 081 approximately, if the quarantine is lifted on May 11. If the infection rate increase, more hospital beds and a bigger ICU staff will be mandatory. The currently 2 650 beds won't be enough in the flexible quarantine2, and five intensive care specialist and four nurses per patient will be needed. CONCLUSION: Measures like mandatory social distancing help delay the saturation of the health care system. However, it's impracticable to maintain them due to a possible economic crisis. Therefore, it's necessary to take action to enhance the ability of the health care system to avoid a collapse.

Pretreatment HIV drug resistance spread within transmission clusters in Mexico City.

BACKGROUND: Pretreatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in Mexico City during the last decade. OBJECTIVES: To infer the HIV genetic transmission network in Mexico City to describe the dynamics of the local HIV epidemic and spread of HIVDR. PATIENTS AND METHODS: HIV pol sequences were obtained by next-generation sequencing from 2447 individuals before initiation of ART at the largest HIV clinic in Mexico City (April 2016 to June 2018). Pretreatment HIVDR was estimated using the Stanford algorithm at a Sanger-like threshold (≥20%). Genetic networks were inferred with HIV-TRACE, establishing putative transmission links with genetic distances <1.5%. We examined demographic associations among linked individuals with shared drug resistance mutations (DRMs) using a ≥ 2% threshold to include low-frequency variants. RESULTS: Pretreatment HIVDR reached 14.8% (95% CI 13.4%-16.2%) in the cohort overall and 9.6% (8.5%-10.8%) to NNRTIs. Putative links with at least one other sequence were found for 963/2447 (39%) sequences, forming 326 clusters (2-20 individuals). The inferred network was assortative by age and municipality (P < 0.001). Clustering individuals were younger [adjusted OR (aOR) per year = 0.96, 95% CI 0.95-0.97, P < 0.001] and less likely to include women (aOR = 0.46, 95% CI 0.28-0.75, P = 0.002). Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). Eight municipalities (out of 75) harboured 65% of persons sharing DRMs. Among all persons sharing DRMs, those sharing K103N were younger (aOR = 0.93, 95% CI 0.88-0.98, P = 0.003). CONCLUSIONS: Our analyses suggest age- and geographically associated transmission of DRMs within the HIV genetic network in Mexico City, warranting continuous monitoring and focused interventions.

Gold(i)-catalyzed nucleophilic cyclization of ß-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study.

The stereospecific gold(i)-catalyzed nucleophilic cyclization of ß-monosubstituted o-(alkynyl)styrenes to produce C-1 functionalized 1H-indenes including challenging substrates and nucleophiles, such as ß-(cyclo)alkyl-substituted o-(alkynyl)styrenes and a variety of alcohols as well as selected electron-rich aromatics, is reported. DFT calculations support the stereochemical outcome of the process that involves the formation of a key cyclopropyl gold carbene intermediate through a regiospecific 5-endo cyclization.

Religious affiliation and the intention to choose psychiatry as a specialty among physicians in training from 11 Latin American countries.

The worldwide scarcity of psychiatrists makes the identification of the factors associated with the intention to choose this specialty an important issue. This study aims to evaluate the association between religious affiliation and the intention to choose psychiatry as a specialty among medical students from 11 Latin American countries. We conducted a cross-sectional, multi-country study that included first- and fifth-year students of 63 medical schools in 11 Latin-American countries between 2011 and 2012. The main outcome and measures were the intention to pursue psychiatry as a specialty over other specialties (yes/no) and religious affiliation (without: atheist/agnostic; with: any religion). A total of 8308 participants were included; 53.6% were women, and the average age was 20.4 (SD = 2.9) years. About 36% were fifth-year students, and 11.8% were not affiliated with any religion. Only 2.6% had the intention to choose psychiatry; the highest proportion of students with the intention to choose psychiatry was among students in Chile (8.1%) and the lowest among students in Mexico (1.1%). After adjusting for demographic, family, academic as well as personal and professional projection variable, we found that those who had no religious affiliation were more likely to report the intention to become a psychiatrist [OR: 2.92 (95%CI: 2.14-4.00)]. There is a strong positive association between not having a religious affiliation and the intention to become a psychiatrist. The possible factors that influence this phenomenon must be evaluated in greater depth, ideally through longitudinal research.

General Synthesis of Alkenyl Sulfides by Palladium-Catalyzed Thioetherification of Alkenyl Halides and Tosylates.

The cross-coupling reaction of alkenyl bromides with thiols catalyzed by palladium complexes derived from inexpensive dppf ligand is reported. These reactions occur under low catalyst loading and in high yields and display wide scope, including the coupling of bulky thiols and trisubstituted bromoolefins, and functional group tolerance. In addition, the thioetherification of less reactive chloroalkenes and, for the first time, alkenyl tosylates was accomplished using a catalyst generated from CyPF tBu alkylbisphosphine ligand.

Gold(i)-catalyzed diastereoselective synthesis of 1-α-oxybenzyl-1H-indenes.

The gold(i)-catalyzed oxycyclization of ß-aryl monosubstituted o-(alkynyl)styrenes gives rise to 1-α-methoxy or 1-α-hydroxybenzyl-1H-indenes in a diastereospecific way. In contrast to ß,ß-disubstituted o-(alkynyl)styrenes, the stereochemical outcome of this process, diastereospecific reaction supports the higher contribution of a gold intermediate with a cyclopropylcarbene-like character.

Molybdenum-Catalyzed Synthesis of Nitrogenated Polyheterocycles from Nitroarenes and Glycols with Reuse of Waste Reduction Byproduct.

A novel domino reduction/imine formation/intramolecular cyclization/oxidation for the efficient synthesis of pyrrolo(indolo)[1,2-a]quinoxalines and pyrrolo(indolo)[3,2-c]-quinolines from readily available nitrobenzenes and glycols is reported. The process utilizes the carbonyl byproduct of the initial dioxomolybdenum(VI)-catalyzed reduction of nitroaromatics with glycols as a reagent for the imine generation. This method represents the first sustainable domino reaction for the preparation of biologically relevant heterocycles that internally incorporates the waste formed in the first step to the final product.

In Silico Prediction of the Toxic Potential of Lupeol.

Lupeol is a natural triterpenoid found in many plant species such as mango. This compound is the principal active component of many traditional herbal medicines. In the past decade, a considerable number of publications dealt with lupeol and its analogues due to the interest in their pharmacological activities against cancer, inflammation, arthritis, diabetes, and heart disease. To identify further potential applications of lupeol and its analogues, it is necessary to investigate their mechanisms of action, particularly their interaction with off-target proteins that may trigger adverse effects or toxicity. In this study, we simulated and quantified the interaction of lupeol and 11 of its analogues toward a series of 16 proteins known or suspected to trigger adverse effects employing the VirtualToxLab. This software provides a thermodynamic estimate of the binding affinity, and the results were challenged by molecular-dynamics simulations, which allow probing the kinetic stability of the underlying protein-ligand complexes. Our results indicate that there is a moderate toxic potential for lupeol and some of its analogues, by targeting and binding to nuclear receptors involved in fertility, which could trigger undesired adverse effects.

Synthesis of Functionalized 1H-Indenes and Benzofulvenes through Iodocyclization of o-(Alkynyl)styrenes.

A convenient method for the preparation of synthetically useful 3-iodoindene derivatives has been developed. This protocol, based on the 5-endo iodocyclization reaction of o-(alkynyl)styrenes, represents one of the scarce examples of halocyclizations using olefins as nucleophilic counterparts and allows the synthesis of both 3-iodo-1H-indenes (from ß-alkyl-ß-alkyl/aryl-o-(alkynyl)styrenes) and 3-iodobenzofulvenes (from ß,ß-diaryl-o-(alkynyl)styrenes) in good yields under mild reaction conditions. In addition, related alkoxyiodocyclization processes are described, which are particularly interesting in their intramolecular version because they allow the synthesis of heteropolycyclic structures containing the indene core. Finally, the usefulness of the prepared 3-iodoindenes has been demonstrated by the synthesis of several polysubstituted indene derivatives through conventional palladium-catalyzed cross-coupling reactions and iodine-lithium exchange processes.

1,3-Dien-5-ynes: Versatile Building Blocks for the Synthesis of Carbo- and Heterocycles.

1,3-Dien-5-ynes have been extensively used as starting materials for the synthesis of a wide number of different carbo- and heterocycles. The aim of this review is to give an overview of their utility in organic synthesis, highlighting the variety of compounds that can be directly accessed from single reactions over these systems. Thus, cycloaromatization processes are initially commented, followed by reactions directed toward the syntheses of five-membered rings, other carbocycles and, finally, heterocycles. The diverse methodologies that have been developed for the synthesis of each of these types of compounds from 1,3-dien-5-ynes are presented, emphasizing the influence of the reaction conditions and the use of additional reagents in the outcome of the transformations.