Stereoselective Cyclopropanation of Multisubstituted Enesulfinamides: Asymmetric Construction of α-Tertiary Cyclopropylamine Derivatives Containing ß-Quaternary Stereocenters.

Enesulfinamides with α,ß,ß-trisubstitution undergo a Simmons-Smith reaction to yield multisubstituted cyclopropylamine derivatives with high stereocontrol. The resulting α-tertiary cyclopropylamine derivatives, which feature ß-quaternary stereocenters bearing two electronically and sterically similar substituents (e.g., methyl and ethyl), are seldom achieved by using conventional methods. By adjusting the stereochemistry of the carbon-carbon double bond and/or sulfinyl group within the enesulfinamides, it is feasible to selectively produce four stereoisomers of the cyclopropylamines, each with different absolute configurations at the α- and ß-carbons.

Stereoselective Construction of Acyclic ß,ß-Disubstituted Enesulfinamides via Conjugate Addition of Organocuprates to α-Substituted α,ß-Unsaturated N-Sulfinyl Ketimines.

In the presence of boron trifluoride, conjugate addition of organocuprates to α-substituted α,ß-unsaturated N-tert-butanesulfinyl ketimines provides facile access to acyclic ß,ß-disubstituted enesulfinamides with high ratios of geometric isomers. Diverse and challenging to synthesize, multisubstituted aza-enolates bearing two electronically and sterically similar ß-substituents, which are important precursors for asymmetric construction of the less accessible acyclic quaternary or tetrasubstituted stereocenters at the α-position of ketimines, can be efficiently prepared in good yields with high stereocontrol.

Prediction models for depression risk among older adults: systematic review and critical appraisal.

OBJECTIVE: To provide an overview of prediction models for the risk of major depressive disorder (MDD) among older adults. METHODS: We conducted a systematic review combined with a meta-analysis and critical appraisal of published studies on existing geriatric depression risk models. RESULTS: The systematic search screened 23,378 titles and abstracts; 14 studies including 20 prediction models were included. A total of 16 predictors were selected in the final model at least twice. Age, physical health, and cognitive function were the most common predictors. Only one model was externally validated, two models were presented with a complete equation, and five models examined the calibration. We found substantial heterogeneity in predictor and outcome definitions across models; important methodological information was often missing. All models were rated at high or unclear risk of bias, primarily due to methodological limitations. The pooled C-statistics of 12 prediction models was 0.83 (95%CI=0.77-0.89). CONCLUSION: The usefulness of all models remains unclear due to several methodological limitations. Future studies should focus on methodological quality and external validation of depression risk prediction models.

Electro-Fenton and Induced Electro-Fenton as Versatile Wastewater Treatment Processes for Decontamination and Nutrient Removal without Byproduct Formation.

It is a long-pursued goal to develop electrified water treatment technology that can remove contaminants without byproduct formation. This study unveiled the overlooked multifunctionality of electro-Fenton (EF) and induced EF (I-EF) processes to remove organics, pathogens, and phosphate in one step without halogenated byproduct formation. The EF and I-EF processes used a sacrificial anode or an induced electrode to generate Fe2+ to activate H2O2 produced from a gas diffusion cathode fed by naturally diffused air. We used experimental and kinetic modeling approaches to illustrate that the •OH generation and radical speciation during EF were not impacted by chloride. More importantly, reactive chlorine species were quenched by H2O2, which eliminated the formation of halogenated byproducts. When applied in treating septic wastewater, the EF process removed >80% COD, >50% carbamazepine (as representative trace organics), and >99% phosphate at a low energy consumption of 0.37 Wh/L. The EF process also demonstrated broad-spectrum disinfection activities in removing and inactivating Escherichia coli, Enterococcus durans, and model viruses MS2 and Phi6. In contrast to electrochemical oxidation (EO) that yielded mg/L level byproducts to achieve the same degree of treatment, EF did not generate byproducts (chlorate, perchlorate, trihalomethanes, and haloacetic acids). The I-EF carried over all the advantages of EF and exhibited even faster kinetics in disinfection and carbamazepine removal with 50-80% less sludge production. Last, using septic wastewater treatment as a technical niche, we demonstrated that iron sludge formation is predictable and manageable, clearing roadblocks toward on-site water treatment applications.

Robust Performance of SARS-CoV-2 Whole-Genome Sequencing from Wastewater with a Nonselective Virus Concentration Method.

The sequencing of human virus genomes from wastewater samples is an efficient method for tracking viral transmission and evolution at the community level. However, this requires the recovery of viral nucleic acids of high quality. We developed a reusable tangential-flow filtration system to concentrate and purify viruses from wastewater for genome sequencing. A pilot study was conducted with 94 wastewater samples from four local sewersheds, from which viral nucleic acids were extracted, and the whole genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was sequenced using the ARTIC V4.0 primers. Our method yielded a high probability (0.9) of recovering complete or near-complete SARS-CoV-2 genomes (>90% coverage at 10× depth) from wastewater when the COVID-19 incidence rate exceeded 33 cases per 100 000 people. The relative abundances of sequenced SARS-CoV-2 variants followed the trends observed from patient-derived samples. We also identified SARS-CoV-2 lineages in wastewater that were underrepresented or not present in the clinical whole-genome sequencing data. The developed tangential-flow filtration system can be easily adopted for the sequencing of other viruses in wastewater, particularly those at low concentrations.

Stereocontrolled α-Allylation of α-Branched N-tert-Butanesulfinyl Ketimines via a Michael-Wittig Cascade for the Construction of Acyclic Quaternary Stereocenters.

A single-flask cascade of Michael addition and Wittig olefination was developed to allow the stereoselective α-allylic alkylation of α-branched N-tert-butanesulfinyl ketimines for the construction of acyclic quaternary stereocenters bearing two sterically and electronically similar substituents. In this process, tBuOK-promoted stereoselective α-deprotonation gives fully substituted aza-enolates with a stereodefined geometry, Michael addition with α,ß-unsaturated phosphonates generates C-C bonds with exceptional stereocontrol, and finally paraformaldehyde trapping of the conjugate addition intermediate generates functionalized α-allylated imines.

Construction of Acyclic Quaternary Stereocenters via Mannich-Type Addition of α,α-Disubstituted N-tert-Butanesulfinyl Ketimines to Isatin-Derived Ketimines.

A Mannich reaction of deprotonated, highly enantioenriched α,α-disubstituted N-tert-butanesulfinyl ketimines with isatin-derived ketimines was developed to prepare 3-amino-3-substituted oxindoles bearing an acyclic quaternary stereogenic carbon substituted with two sterically similar groups. The excellent stereocontrol of the deprotonation enabled the formation of metalloenamine intermediates with stereodefined geometry, while the precise facial selectivity of the C-C bond formation allowed the construction of contiguous quaternary and tetrasubstituted stereocenters with excellent stereoselectivity.