Anodic oxidation triggered divergent 1,2- and 1,4-group transfer reactions of ß-hydroxycarboxylic acids enabled by electrochemical regulation.

We report a set of electrochemically regulated protocols for the divergent synthesis of ketones and ß-keto esters from the same ß-hydroxycarboxylic acid starting materials. Enabled by electrochemical control, the anodic oxidation of carboxylic acids proceeded in either a one-electron or a two-electron pathway, leading to a 1,4-aryl transfer or a semipinacol-type 1,2-group transfer product with excellent chemoselectivity. The 1,4-aryl transfer represents an unprecedented example of carbon-to-oxygen group transfer proceeding via a radical mechanism. In contrast to previously reported radical group transfer reactions, this 1,4-group transfer process features the migration of electron-rich aryl substituents. Furthermore, with these chemoselective electrochemical oxidation protocols, a range of ketones and ß-keto esters including those possessing a challenging-to-access medium-sized ring could be synthesized in excellent yields.

Discovery of heterocyclic replacements for the coumarin core of anti-tubercular FadD32 inhibitors.

Previous work established a coumarin scaffold as a starting point for inhibition of Mycobacterium tuberculosis (Mtb) FadD32 enzymatic activity. After further profiling of the coumarin inhibitor 4 revealed chemical instability, we discovered that a quinoline ring circumvented this instability and had the advantage of offering additional substitution vectors to further optimize. Ensuing SAR studies gave rise to quinoline-2-carboxamides with potent anti-tubercular activity. Further optimization of ADME/PK properties culminated in 21b that exhibited compelling in vivo efficacy in a mouse model of Mtb infection.

Assessment of the Spatial and Temporal Variations of Water Quality for Agricultural Lands with Crop Rotation in China by Using a HYPE Model.

Many water quality models have been successfully used worldwide to predict nutrient losses from anthropogenically impacted catchments, but hydrological and nutrient simulations with limited data are difficult considering the transfer of model parameters and complication of model calibration and validation. This study aims: (i) to assess the performance capabilities of a new and relatively more advantageous model, namely, Hydrological Predictions for the Environment (HYPE), that simulates stream flow and nutrient load in agricultural areas by using a multi-site and multi-objective parameter calibration method and (ii) to investigate the temporal and spatial variations of total nitrogen (TN) and total phosphorous (TP) concentrations and loads with crop rotation by using the model for the first time. A parameter estimation tool (PEST) was used to calibrate parameters. Results show that the parameters related to the effective soil porosity were highly sensitive to hydrological modeling. N balance was largely controlled by soil denitrification processes. P balance was influenced by the sedimentation rate and production/decay of P in rivers and lakes. The model reproduced the temporal and spatial variations of discharge and TN/TP relatively well in both calibration (2006-2008) and validation (2009-2010) periods. Among the obtained data, the lowest Nash-Suttclife efficiency of discharge, daily TN load, and daily TP load were 0.74, 0.51, and 0.54, respectively. The seasonal variations of daily TN concentrations in the entire simulation period were insufficient, indicated that crop rotation changed the timing and amount of N output. Monthly TN and TP simulation yields revealed that nutrient outputs were abundant in summer in terms of the corresponding discharge. The area-weighted TN and TP load annual yields in five years showed that nutrient loads were extremely high along Hong and Ru rivers, especially in agricultural lands.