Enantioselective Michael Addition of Pyrroles with Nitroalkenes in Aqueous Media Catalyzed by a Water-Soluble Catalyst

A new water-soluble catalytic system was developed and used in an enantioselective Michael addition of pyrroles with nitroalkenes in water to afford nitroethylpyrrole derivatives with both excellent yields and ee values

Aryliodonium Salt-Induced Regioselective Access to <i>meta-</i>Substituted Anilines by Arylation of Azoles

A highly efficient aryliodonium salt-induced regioselective access to meta-substituted anilines by arylation of azoles has been developed under catalyst-free conditions. This efficient transformation provides a facile and scalable approach to a wide range of biologically active N-arylazoles with moderate to high yields. According to the control experiments, two plausible pathways, including a Michael pathway and a free radical coupling pathway, for the reaction were proposed

Coimmobilization of β‑Agarase and α‑Neoagarobiose Hydrolase for Enhancing the Production of 3,6-Anhydro‑l‑galactose

Here we report a simple and efficient method to produce 3,6-anhydro-l-galactose (l-AHG) and agarotriose (AO3) in one step by a multienzyme system with the coimmobilized β-agarase AgWH50B and α-neoagarobiose hydrolase K134D. K134D was obtained by AgaWH117 mutagenesis and showed improved thermal stability when immobilized via covalent bonds on functionalized magnetic nanoparticles. The obtained multienzyme biocatalyst was characterized by Fourier transform infrared spectroscopy (FTIR). Compared with free agarases, the coimmobilized agarases exhibited a relatively higher agarose-to-l-AHG conversion efficiency. The yield of l-AHG obtained with the coimmobilized agarases was 40.6%, which was 6.5% higher than that obtained with free agarases. After eight cycles, the multienzyme biocatalyst still preserved 46.4% of the initial activity. To the best of our knowledge, this is the first report where two different agarases were coimmobilized. These results demonstrated the feasibility of the new method to fabricate a new multienzyme system onto magnetic nanoparticles via covalent bonds to produce l-AHG

Clara Pitman and Alice Priest, Westbrook Seminary, Fall Term 1899

Clara Elizabeth Pitman (North Conway, N.H.) and Alice Priest (Canton, N.Y.) are listed in the Catalogue of the Officers and Students of Westbrook Seminary for the Academic Year Ending June 22, 1900, as Westbrook Seminary Class of 1901 and Westbrook Seminary Class of 1902, respectively. In this 1899 sepia toned photograph mounted on a black backing, the two girls stand, with linked arms, outside Hersey Hall. Clara holds a plaid stadium blanket and Alice has a punching ball hanging from a cord around her neck. She leans her head on Clara\u27s shoulder. Both girls wear dark skirts and white blouses. Clara\u27s hair is piled Gibson Girl style on the top of her head.https://dune.une.edu/wchc_photos_students1900s/1002/thumbnail.jp

Binding Kinetics Toolkit for Analyzing Transient Molecular Conformations and Computing Free Energy Landscapes

Understanding ligand binding kinetics and thermodynamics, which involves investigating the free, transient, and final complex conformations, is important in fundamental studies and applications for chemical and biomedical systems. Examining the important but transient ligand–protein-bound conformations, in addition to experimentally determined structures, also provides a more accurate estimation for drug efficacy and selectivity. Moreover, obtaining the entire picture of the free energy landscape during ligand binding/unbinding processes is critical in understanding binding mechanisms. Here, we present a Binding Kinetics Toolkit (BKiT) that includes several utilities to analyze trajectories and compute a free energy and kinetics profile. BKiT uses principal component space to generate approximated unbinding or conformational transition coordinates for accurately describing and easily visualizing the molecular motions. We implemented a new partitioning approach to assign indexes along the approximated coordinates that can be used as milestones or microstates. The program can generate input files to run many short classical molecular dynamics simulations and uses milestoning theory to construct the free energy profile and estimate binding residence time. We first validated the method with a host–guest system, aspirin unbinding from β-cyclodextrin, and then applied the protocol to pyrazolourea compounds and cyclin-dependent kinase 8 and cyclin C complexes, a kinase system of pharmacological interest. Overall, our approaches yielded good agreement with published results and suggest ligand design strategies. The computed unbinding free energy landscape also provides a more complete picture of ligand–receptor binding barriers and stable local minima for deepening our understanding of molecular recognition. BKiT is easy to use and has extensible features for future expansion of utilities for postanalysis and calculations

Copper-Catalyzed Enantioselective Henry Reaction of β,γ‑Unsaturated α‑Ketoesters with Nitromethane in Water

A highly enantioselective Henry reaction of β,γ-unsaturated α-ketoesters with nitromethane in water by virtue of chiral copper complexes has been developed. A series of unsaturated β-nitro-α-hydroxy esters bearing tetrasubstituted carbon stereocenters were obtained exclusively with high yields and excellent enantioselectivities. This method could avoid tedious anaerobic anhydrous manipulation and reduce the environmental pollution caused by organic solvents

Copper-Catalyzed Enantioselective Hetero-Diels–Alder Reaction of Danishefsky’s Diene with Glyoxals

The highly enantioselective hetero-Diels–Alder reaction of Danishefsky’s diene with glyoxals was developed by virtue of a readily accessible chiral copper catalyst. This efficient transformation provided a facile and scalable access to a wide range of biologically active dihydropyrones with a high level of enantioselectivities. Moreover, the substrate scope of this reaction could be extended to isatins with this catalytic system. More importantly, the mechanism involved in this reaction was proposed on the basis of the unambiguous structures of intermediates