Lasmiditan presents a unique pyridinoyl-piperidine scaffold not found in any other antimigraine class. Its chemical structure and pharmacological profile clearly distinguish it from the triptans. The potency and selectivity of lasmiditan make it ideally suited to definitively test the involvement of 5-HT(1F) receptors in migraine headache therapy.

Cyclobutanes and cyclobutenes are important structural motifs found in numerous biologically significant molecules, and they are useful intermediates for chemical synthesis. Consequently, [2+2] cycloadditions to access cyclobutanes and cyclobutenes have been established to be particularly useful transformations. Within the last 10 years, an increase in the frequency of publications for catalytic enantioselective [2+2] cycloadditions has occurred. These reactions provide access to a wide array of enantiomerically enriched chemical diversity that was not previously attainable. Described in this review are the advances made in catalytic enantioselective [2+2] cycloadditions to access cyclobutanes and cyclobutenes.

π-π Interaction is a direct attractive non-covalent interaction between aromatic moieties, playing an important role in DNA stabilization, drug intercalation, etc. Aromatic rings interact through several different conformations including face-to-face, T-shaped, and offset stacked conformation. Previous quantum calculations indicated that T-shaped and offset stacked conformations are preferred for their smaller electron repulsions. However, substitution group on aromatic ring could have a great impact on π-π interaction by changing electron repulsion force between two rings. To investigate π-π interaction between ligand and aromatic side chain of protein, Brookhaven Protein Data Bank was analyzed. We extracted isolated dimer pairs with the aim of excluding multiple π-π stacking effects and found that T-shaped conformation is prevalent among aromatic interaction between phenyl ring of ligand and protein, which corresponds with the phenomenon of Phe-Phe interactions in small peptide. Specifically, for the non-substitution model, both Phe-Phe and Phenyl-Phe exhibit a favored T-shaped conformation whose dihedral angle is around 50°-70° and centroid distance is between 5.0 and 5.6 Å. However, it could be changed by substituent effect. The hydroxyl group could contact in the case of Tyr-Tyr pairs, while they point away from phenyl plane in Phe-Tyr pairs.

Catalytic enantioselective [2 + 2] cycloadditions between allenoates and alkenes is disclosed. The method functions well for a variety of alkenes, and the products are generated with excellent levels of enantioselectivity. One of the most significant aspects of the present method is that unactivated alkenes are suitable substrates for this method, which is distinctly different from nearly all other catalytic enantioselective [2 + 2] cycloaddition methods.

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Chalkophores are bacterial natural products that chelate and transport extracellular copper. The diisonitrile natural product SF2768 was first isolated from a Streptomyces species as an antifungal antibiotic and has more recently been characterized as a bacterial chalkophore and potential virulence factor. Herein, we report a modular synthesis of SF2768 and related acyclic analogues, allowing assignment of syn-stereochemistry across the central lactol ring. The copper-binding properties of these diisonitriles have also been studied.

Treatment of an electron-rich benzyl ether with DDQ at ambient temperature followed by addition of a silyl enol ether undergoes a C-C bond-forming reaction to afford 3-alkoxy-3-phenyl-propionyl compound. This is a general reaction and works well with a variety of silyl enol ethers to give carbonyl products in yields ranging from 10 to 85%.

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