Enantioselective Boronate Additions to <i>N</i>-Acyl Quinoliniums Catalyzed by Tartaric Acid

Tartaric acid catalyzes the asymmetric addition of vinylboronates to <i>N</i>-acyl quinoliniums, affording highly enantioenriched dihydroquinolines. The catalyst serves to activate the boronate through a ligand-exchange reaction and generates the <i>N</i>-acyl quinolinium in situ from the stable quinoline-derived <i>N</i>,<i>O</i>-acetal

Enantioselective Synthesis of 1,2-Dihydro­naph­thalene-1-carbaldehydes by Addition of Boronates to Isochromene Acetals Catalyzed by Tartaric Acid

Tartaric acid is an ideal asymmetric catalyst as it is abundant, cheap, and environmentally friendly. (+)-Tartaric acid was found to catalyze a novel enantioselective [4 + 2] cycloaddition of isochromene acetals and vinylboronates. A variety of substituted isochromene acetals were tolerated, furnishing the desired dihydro­naph­thalenes and dihydro­benzo­fluorene products in good yields. High enantiomeric ratios (up to 98.5:1.5) and excellent diastereoselectivities (all >99:1) were observed employing 10 mol % of (+)-tartaric acid as the catalyst, in combination with 5 mol % of Ho­(OTf)₃

High-Throughput Screen in Cryptococcus neoformans Identifies a Novel Molecular Scaffold That Inhibits Cell Wall Integrity Pathway Signaling

Cryptococcus neoformans is one of the most important human fungal pathogens; however, no new therapies have been developed in over 50 years. Fungicidal activity is crucially important for an effective anticryptococal agent and, therefore, we screened 361,675 molecules against C. neoformans using an adenylate kinase release assay that specifically detects fungicidal activity. A set of secondary assays narrowed the set of hits to molecules that interfere with fungal cell wall integrity and identified three benzothioureas with low in vitro mammalian toxicity and good in vitro anticryptococcal (minimum inhibitory concentration = 4 μg/mL). This scaffold inhibits signaling through the cell wall integrity MAP kinase cascade. Structure–activity studies indicate that the thiocarbonyl moiety is crucial for activity. Genetic and biochemical data suggest that benzothioureas inhibit signaling upstream of the kinase cascade. Thus, the benzothioureas appear to be a promising new scaffold for further exploration in the search for new anticryptococcal agents