No abstract

Seventeen fibrous glasses of diverse type or dimensional distribution induced different incidences of malignant mesenchymal neoplasms when implanted in the pleurae of female Osborne-Mendel rats for periods of more than 1 year. Neoplastic response correlated well with the dimensional distribution of fibers. Fibers less than or equal to 1.5 mu in diameter and greater than 8 mu in length yielded the highest probability of pleural sarcomas, and probability trends suggested that pleural sarcoma incidence increased with increasing lengths of fibers with diameters of less than 1.5 mu, Morphologic observations indicated that fibers less than or equal to 8 mu in length were inactivated by phagocytosis. In fibers greater than 8 mu in length, the correlation of carcinogenicity witth increasing length was difficult to explain. Since neoplastic response to a variety of types of durable fibers, particularly asbestos fibers, was similar, our experiments reinforce the idea that the carcinogenicity of fibers depends on dimension and durability rather than physicochemical properties and emphasize that all respirable fibers be viewed with caution.

Difluoromethylene-containing compounds have attracted substantial research interest over the past decades for their ability to mimic biological functions of traditional functional groups while providing a wide variety of pharmacological benefits bestowed by the C–F bond. We report a novel strategy to access RCF2Br-containing heterocycles by regio- and enantioselective bromocyclization of difluoroalkenes enabled by chiral anion phase-transfer catalysis. The utility of this methodology was highlighted through a synthesis of an analogue of efavirenz, a drug used for treating HIV. Additionally, the synthetic versatility of the CF2Br intermediates was showcased through functionalization to a variety of enantioenriched α,α-difluoromethylene-containing products.

No abstract

The defined structure of molecules bearing multiple stereogenic axes is of increasing relevance to materials science, pharmaceuticals, and catalysis. However, catalytic enantioselective approaches to control multiple stereogenic axes remain synthetically challenging. We report the catalytic synthesis of two-axis terphenyl atropisomers, with complementary strategies to both chlorinated and brominated variants, formed with high diastereo-and enantioselectivity. The chemistry proceeds through a sequence of two distinct dynamic kinetic resolutions: first, an atroposelective ring-opening of Bringmann-type lactones produces a product with one established axis of chirality; second, a stereoselective arene halogenation delivers the product with the second axis of chirality established. In order to achieve these results, a class of Brønsted basic guanidinylated peptides, which catalyze an efficient atroposelective chlorination, is reported for the first time. In addition, a complementary bromination is reported, which also establishes the second stereogenic axis. These bromo-terphenyls are accessible following the discovery that chiral anion phase transfer catalysis by C 2 -symmetric phosphoric acids allows catalyst control in the second stereochemistry-determining event. Accordingly, we established the fully catalyst-controlled stereodivergent synthesis of all possible chlorinated stereoisomers, while also demonstrating diastereodivergence in the brominated variants, with significant levels of enantioselectivity in both cases.