Despite an abundance of online databases providing access to chemical data, there is increasing demand for high-quality, structure-curated, open data to meet the various needs of the environmental sciences and computational toxicology communities. The U.S. Environmental Protection Agency’s (EPA) web-based CompTox Chemistry Dashboard is addressing these needs by integrating diverse types of relevant domain data through a cheminformatics layer, built upon a database of curated substances linked to chemical structures. These data include physicochemical, environmental fate and transport, exposure, usage, in vivo toxicity, and in vitro bioassay data, surfaced through an integration hub with link-outs to additional EPA data and public domain online resources. Batch searching allows for direct chemical identifier (ID) mapping and downloading of multiple data streams in several different formats. This facilitates fast access to available structure, property, toxicity, and bioassay data for collections of chemicals (hundreds to thousands at a time). Advanced search capabilities are available to support, for example, non-targeted analysis and identification of chemicals using mass spectrometry. The contents of the chemistry database, presently containing ~ 760,000 substances, are available as public domain data for download. The chemistry content underpinning the Dashboard has been aggregated over the past 15 years by both manual and auto-curation techniques within EPA’s DSSTox project. DSSTox chemical content is subject to strict quality controls to enforce consistency among chemical substance-structure identifiers, as well as list curation review to ensure accurate linkages of DSSTox substances to chemical lists and associated data. The Dashboard, publicly launched in April 2016, has expanded considerably in content and user traffic over the past year. It is continuously evolving with the growth of DSSTox into high-interest or data-rich domains of interest to EPA, such as chemicals on the Toxic Substances Control Act listing, while providing the user community with a flexible and dynamic web-based platform for integration, processing, visualization and delivery of data and resources. The Dashboard provides support for a broad array of research and regulatory programs across the worldwide community of toxicologists and environmental scientists.

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The CompTox Chemistry Dashboard: a community data resource for environmental chemistry

Quinolines and structurally related heterocycles as antimalarials

New economic and environmentally benign methods for achieving carbon–carbon bond formation are in constant demand. Here, a remarkably efficient and functional-group-tolerant, metal-free reductive cross-coupling of carbonyl compounds with boronic acids is described.

Metal-free carbon–carbon bond-forming reductive coupling between boronic acids and tosylhydrazones

The collection of chemical structure information and associated experimental data for quantitative structure–activity/property relationship (QSAR/QSPR) modeling is facilitated by an increasing number of public databases containing large amounts of useful data. However, the performance of QSAR models highly depends on the quality of the data and modeling methodology used. This study aims to develop robust QSAR/QSPR models for chemical properties of environmental interest that can be used for regulatory purposes. This study primarily uses data from the publicly available PHYSPROP database consisting of a set of 13 common physicochemical and environmental fate properties. These datasets have undergone extensive curation using an automated workflow to select only high-quality data, and the chemical structures were standardized prior to calculation of the molecular descriptors. The modeling procedure was developed based on the five Organization for Economic Cooperation and Development (OECD) principles for QSAR models. A weighted k-nearest neighbor approach was adopted using a minimum number of required descriptors calculated using PaDEL, an open-source software. The genetic algorithms selected only the most pertinent and mechanistically interpretable descriptors (2–15, with an average of 11 descriptors). The sizes of the modeled datasets varied from 150 chemicals for biodegradability half-life to 14,050 chemicals for logP, with an average of 3222 chemicals across all endpoints. The optimal models were built on randomly selected training sets (75%) and validated using fivefold cross-validation (CV) and test sets (25%). The CV Q2 of the models varied from 0.72 to 0.95, with an average of 0.86 and an R2 test value from 0.71 to 0.96, with an average of 0.82. Modeling and performance details are described in QSAR model reporting format and were validated by the European Commission’s Joint Research Center to be OECD compliant. All models are freely available as an open-source, command-line application called OPEn structure–activity/property Relationship App (OPERA). OPERA models were applied to more than 750,000 chemicals to produce freely available predicted data on the U.S. Environmental Protection Agency’s CompTox Chemistry Dashboard.

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OPERA models for predicting physicochemical properties and environmental fate endpoints

This transformation has received tremendous attention in the field of organic synthesis due to its ability to form synthetically versatile cyclopentenones. With appropriately substituted dienones, the orbital reorganization implants new stereocenters in the oxyallyl cation (3), which are retained in the pentacyclic product (5). In terms of the reaction mechanism (Scheme 1), the coordination of either a Brønsted or a Lewis acid (LA) promoter to the dienone (1) induces the electrocyclization of the pentadienyl cation (2). Consistent with the principle of conservation of orbital symmetry, a conrotatory closure proceeds to form an oxyallyl cation (3), having an anti relationship between R and R. This intermediate has the potential to go through diverse reaction pathways such as carbocationic rearrangements or interception from 3 with external nucleophiles. Traditionally, elimination of a proton generates a promoter bound enolate (4) that furnishes a cyclopentenone (5) upon reprotonation. Since the 2005 reviews of the Nazarov reaction by Frontier and Collison, Tius, and Pellissier, a number of new catalytic and stoichiometric reactions 15, 19–60] have been reported that address synthetic problems associated with this transformation. This review will discuss the catalytic advances in the Nazarov cyclization since 2005, including the design of new catalysts, formulation of new conditions, variations of the electrocyclization, tandem processes, strategies that result in enantioinduction, and application to natural product synthesis. The catalysts have been categorized into the following subclasses: Brønsted acids, organocatalysts, heterogeneous catalysts, Lewis acids including transition-metal catalysts, and a supramolecular host.

Catalytic Nazarov Cyclization: The State of the Art

Thiophene containing triarylmethanes as antitubercular agents.

Effect of substituents on diarylmethanes for antitubercular activity.

A convenient synthesis of chiral amino acid derived 3,4-dihydro-2H-benzo[b][1,4]thiazines and antibiotic levofloxacin

Design, synthesis and antimalarial activity of benzene and isoquinoline sulfonamide derivatives

A concise and general route to synthesize a new class of [6-5-6] tricyclic core embedded polyheterocycles has been accomplished using diastereoselective Nazarov cyclization with an overall yield of 35–40%. Versatility of this synthetic route has also been demonstrated by accessing a variety of [6-5-5] tricyclic core incorporated polycycles. It was observed that the efficiency of cyclization depends upon the impact of polarization on the reacting systems. Amongst the various Lewis and Bronsted acids screened for cyclization, triflic acid was found to be the most effective catalyst.

Application of Nazarov cyclization to access [6-5-6] and [6-5-5]tricyclic core embedded new heterocycles: an easy entry to structures related to Taiwaniaquinoids

Maloy Kumar Parai

Papers

Thiophene containing triarylmethanes as antitubercular agents.

Effect of substituents on diarylmethanes for antitubercular activity.

A convenient synthesis of chiral amino acid derived 3,4-dihydro-2H-benzo[b][1,4]thiazines and antibiotic levofloxacin

Design, synthesis and antimalarial activity of benzene and isoquinoline sulfonamide derivatives

Application of Nazarov cyclization to access [6-5-6] and [6-5-5]tricyclic core embedded new heterocycles: an easy entry to structures related to Taiwaniaquinoids