Teorethical studies of the stability of 8a-alkyll-1,2,3,4,6,8a- hexahydronaphtalen-1-ones using semiempirical methods

The Birch alkylation products are very unstable. We are showing, in this communication, the results of a theoretical study that compares different decomposition reaction mechanisms. The conclusions are in agreement with our experimental results.Facultad de Ciencias Exacta

Teorethical studies of the stability of 8a-alkyll-1,2,3,4,6,8a- hexahydronaphtalen-1-ones using semiempirical methods

The Birch alkylation products are very unstable. We are showing, in this communication, the results of a theoretical study that compares different decomposition reaction mechanisms. The conclusions are in agreement with our experimental results.Facultad de Ciencias Exacta

Advances in the Development of Mid-Infrared Integrated Devices for Interferometric Arrays

This article reports the advances on the development of mid-infrared integrated optics for stellar interferometry. The devices are fabricated by laser writing techniques on chalcogenide glasses. Laboratory characterizaton is reported and analyzed.Comment: 12 pages, 9 figures, SPIE Astronomical Telescopes and Instrumentatio

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence.Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening.Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM).Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle

Foreword to the Proceedings of the 12th National Symposium of Organic Chemistry "Dr. Eduardo Guerreiro", Los Cocos (Córdoba), Argentina, 14-17 November 1999

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Foreword to the Proceedings of the 12th National Symposium of Organic Chemistry "Dr. Eduardo Guerreiro", Los Cocos (Córdoba), Argentina, 14-17 November 1999

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Proceedings of the 12th National Symposium of Organic Chemistry (XII SINAQO), Los Cocos, Cordoba, Argentina, 14-17 November 1999

This Paper is downloadable at http://www.mdpi.org/molecules/papers/50300252.pd

Tuning the Lewis acid phenol ortho-prenylation as a molecular diversity tool

A diversity-oriented approach for the synthesis of various structurally different prenylated alcohols from readily accessible and common precursors was developed. With varying approaches, this article describes some successful examples of a Friedel–Crafts alkylation using methoxyphenols and different prenyl alcohols (geraniol and (E,E)-farnesol). We demonstrated that just by varying the stoichiometry of the Lewis acid used, the course of the reaction can be shifted to produce the alkylated or the cyclized product. Eighteen unique products were obtained with good isolated yields by direct alkylation with or without a consecutive π-cationic cyclization

Progress towards instrument miniaturisation for mid-IR long-baseline interferometry

We report recent results on passive mid-infrared integrated optics from the project Advanced Laser-writing for Stellar Interferometry and shortly describe the perspectives of their hybridisation with active components for the benefit of the spectro-interferometry technique