Switchable Enantio- and Diastereoselective Michael Additions of ß-Keto Amides to Nitroolefins: Crystallization-Based Inversion of Kinetic Stereocontrol.

Asymmetric catalytic reactions rely on chiral catalysts that induce highly ordered transition states capable of imparting stereoselectivity in the bond-forming step(s). Productive deviations from this paradigm are rare yet hold the potential for accessing different stereoisomers using the same catalyst. Here, we present an enantio- and diastereoselective Michael addition of ß-keto amides to nitroolefin electrophiles proceeding via an unusual scenario where the kinetic diastereocontrol imparted by the catalyst may be overridden by crystallization to provide the complementary stereoisomer of the product.

No impairment of contextual fear memory consolidation by oxytocin receptor antagonism in male rats.

Oxytocin is a peptide released into brain regions associated with the processing of aversive memory and threat responses. Given the expression of oxytocin receptors across this vigilance surveillance system of the brain, we investigated whether pharmacological antagonism of the receptor would impact contextual aversive conditioning and memory. Adult male rats were conditioned to form an aversive contextual memory. The effects of peripheral administration of either the competitive antagonist Atosiban or noncompetitive antagonist L-368,899 were compared to saline controls. Oxytocin receptor antagonism treatment did not significantly impact the consolidation of aversive contextual memory in any of the groups. We conclude that peripheral antagonism of oxytocin signalling did not impact the formation of aversive memory.

Crystallization-Enabled Stereoconvergent Michael Additions of ß-Keto Esters to Nitroolefins.

Asymmetric Michael additions are powerful tools to meet the growing need for stereochemically complex products. While 1,3-dicarbonyls are common nucleophiles, the successful use of configurationally unstable ß-keto esters in diastereoselective variants remains understudied. In this Letter, crystalline ß-keto esters were leveraged in a two-phase, one-pot merger of an asymmetric Michael addition with a crystallization-induced diastereomer transformation. Tuning the crystallinity of ß-keto ester adducts enabled stereoconvergence of the products, which were isolated by filtration.

Reactivity to conditioned threat cues is distinct from exploratory drive in the elevated plus maze.

Fear and anxiety are adaptive states that allow humans and animals alike to respond appropriately to threatening cues in their environment. Commonly used tasks for studying behaviour akin to fear and anxiety in rodent models are Pavlovian threat conditioning and the elevated plus maze (EPM), respectively. In threat conditioning the rodents learn to associate an aversive event with a specific stimulus or context. The learnt association between the two stimuli (the 'memory') can then be recalled by re-exposing the subject to the conditioned stimulus. The elevated plus maze is argued to measure the agoraphobic avoidance of the brightly lit open maze arms in crepuscular rodents. These two tasks have been used extensively, yet research into whether they interact is scarce. We investigated whether recall of an aversive memory, across contextual, odour or auditory modalities, would potentiate anxiety-like behaviour in the elevated plus maze. The data did not support that memory recall, even over a series of time points, could influence EPM behaviour. Furthermore, there was no correlation between EPM behaviour and conditioned freezing in independent cohorts tested in the EPM before or after auditory threat conditioning. Further analysis found the production of 22 kHz ultrasonic vocalisations revealed the strongest responders to a conditioned threat cue. These results are of particular importance for consideration when using the EPM and threat conditioning to identify individual differences and the possibility to use the tasks in batteries of tests without cross-task interference.

The bed nucleus of the stria terminalis in threat detection: task choice and rodent experience.

Behavioural reactivity to potential threat is used to experimentally refine models of anxiety symptoms in rodents. We present a short review of the literature tying the most commonly used tasks to model anxiety symptoms to functional recruitment of bed nucleus of the stria terminalis circuits (BNST). Using a review of studies that investigated the role of the BNST in anxiety-like behaviour in rodents, we flag the certain challenges for the field. These stem from inconsistent methods of reporting the neuroanatomical BNST subregions and the interpretations of specific behaviour across a wide variety of tasks as 'anxiety-like'. Finally, to assist in interpretation of the findings, we discuss the potential interactions between typically used 'anxiety' tasks of innate behaviour that are potentially modulated by the social and individual experience of the animal.