James Sanderson

Photoaffinity probes were designed to target cyclin‐dependent kinases (CDKs), which can be regarded as the timekeepers of cellular processes. As reported by J. T. Bush and co‐workers in their Research Article (DOI: https://doi.org/10.1002/anie.20190632110.1002/anie.201906321), these probes competitively enrich CDKs from cell lysates, and a biochemical photoaffinity displacement assay was developed to measure compound potency. The seesaw represents the balance of competition between the photoaffinity probe and competitor compound.

We report a common strategy to facilitate the syntheses of the polycyclic alkaloids (−)‐FR901483 ( 1 ) and (+)‐TAN1251C ( 2 ). A divergent synthetic strategy provides access both natural products through a pivotal spirolactam intermediate ( 3 ), which can be accessed on a gram‐scale. A photocatalytic olefin hydroaminoalkylation brings together three readily available building blocks and forges the majority of the carbon framework present in 1 and 2 in a single operation, leading to concise total syntheses. The complexity‐generating photocatalytic process also provides direct access to novel non‐racemic spirolactam scaffolds that are likely to be of interest to early‐stage drug discovery programs

Nature, Published online: 29 October 2019; doi:10.1038/d41586-019-03263-3

Government offers of new funds for UK scientists could be unaffordable.

Bursting the bubble: Quick, easy and accurate Arrhenius plots from a single experiment were obtained. By using a new device for quantifying gases or gas mixtures based on the simple principle of bubble counting, it is possible to follow reaction kinetics down to volume step sizes of 8–12 μL.

Abstract

We present a new device for quantifying gases or gas mixtures based on the simple principle of bubble counting. With this device, we can follow reaction kinetics down to volume step sizes of 8–12 μL. This enables the accurate determination of both time and size of these gas quanta, giving a very detailed kinetic analysis. We demonstrate this method and device using ammonia borane hydrolysis as a model reaction, obtaining Arrhenius plots with over 300 data points from a single experiment. Our device not only saves time and avoids frustration, but also offers more insight into reaction kinetics and mechanistic studies. Moreover, its simplicity and low cost open opportunities for many lab applications.

Transition‐metal‐catalyzed cross‐coupling chemistry can be regarded as one of the most powerful protocols to construct carbon‐carbon bonds. While the field is still dominated by palladium catalysis, there is an increasing interest to develop protocols which utilize cheaper and more sustainable metal sources. Herein, we report a selective, practical and fast iron‐based cross‐coupling reaction which enables the formation of Csp–Csp3 and Csp2–Csp3 bonds. In a telescoped flow process, the reaction can be combined with the Grignard reagent synthesis. Moreover, flow allows to avoid the use of a supporting ligand without eroding the reaction selectivity.

The doctoral advisor—typically the principal investigator (PI)—is often characterized as a singular or primary mentor who guides students using a cognitive apprenticeship model. Alternatively, the “cascading mentorship” model describes the members of laboratories or research groups receiving mentorship from more senior laboratory members and providing it to more junior members...

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

Chiral couplings made easy: Chiral secondary alkylzinc reagents undergo stereoselective palladium‐catalyzed cross‐coupling reactions with alkenyl and aryl halides. These chiral mixed dialkylzincs are configurationally stable at room temperature for several hours. DFT calculations were performed to rationalize the overall retention in the catalytic cycle. This method was applied in the total synthesis of the sesquiterpenes (S)‐ and (R)‐curcumene.

Abstract

We report palladium‐catalyzed cross‐coupling reactions of chiral secondary non‐stabilized dialkylzinc reagents, prepared from readily available chiral secondary alkyl iodides, with alkenyl and aryl halides. This method provides α‐chiral alkenes and arenes with very high retention of configuration (dr up to 98:2) and satisfactory overall yields (up to 76 % for 3 reaction steps). The configurational stability of these chiral non‐stabilized dialkylzinc reagents was determined and exceeded several hours at 25 °C. DFT calculations were performed to rationalize the stereoretention during the catalytic cycle. Furthermore, the cross‐coupling reaction was applied in an efficient total synthesis of the sesquiterpenes (S)‐ and (R)‐curcumene with control of the absolute stereochemistry.