gem-Difluoroallylation of Aryl Halides and Pseudo Halides with Difluoroallylboron Reagents in High Regioselectivity.

We report the palladium-catalyzed gem-difluoroallylation of aryl halides and pseudo halides with 3,3-difluoroallyl boronates in high yield with high regioselectivity, and we report the preparation of the 3,3-difluoroallyl boronate reactants by a copper-catalyzed defluorinative borylation of inexpensive gaseous 3,3,3-trifluoropropene with bis(pinacolato)diboron. The gem-difluoroallylation of aryl and heteroaryl bromides proceeds with low catalyst loading (0.1 mol % [Pd]) and tolerates a wide range of functional groups, including primary alcohols, secondary amines, ethers, ketones, esters, amides, aldehydes, nitriles, halides, and nitro groups. This protocol extends to aryl iodides, chlorides, and triflates, as well as substituted difluoroallyl boronates, providing a versatile synthesis of gem-difluoroallyl arenes that we show to be valuable intermediates to a series of fluorinated building blocks.

Total Synthesis of (+)-Cytosporolide A via a Biomimetic Hetero-Diels-Alder Reaction.

The first total synthesis of (+)-cytosporolide A was achieved by a biomimetic hetero-Diels-Alder reaction of (-)-fuscoatrol A with o-quinone methide generated from (+)-CJ-12,373. The dienophile, highly oxygenated caryophyllene sesquiterpenoid (-)-fuscoatrol A, was synthesized from the synthetic intermediate in our previous total synthesis of (+)-pestalotiopsin A. The o-quinone methide precursor, isochroman carboxylic acid (+)-CJ-12,373, was synthesized through a Kolbe-Schmitt reaction and an oxa-Pictet-Spengler reaction. The hetero-Diels-Alder reaction of these two compounds proceeded with complete chemo-, regio-, and stereoselectivity to produce the complicated pentacyclic ring system of the cytosporolide skeleton. This total synthesis unambiguously demonstrates that natural cytosporolide A has the structure previously suggested.

Asymmetric construction of all-carbon quaternary stereocenters by chiral-auxiliary-mediated Claisen rearrangement and total synthesis of (+)-bakuchiol.

An asymmetric Claisen rearrangement using Oppolzer’s camphorsultam was developed. Under thermal conditions, a geraniol-derived substrate underwent the rearrangement with good stereoselectivity. The absolute configuration of the newly formed all-carbon quaternary stereocenter was confirmed by the total synthesis of (+)-bakuchiol from the rearrangement product.

Direct Arylation of Simple Arenes with Aryl Bromides by Synergistic Silver and Palladium Catalysis.

The direct, catalytic arylation of simple arenes in small excess with aryl bromides is disclosed. The developed method does not require the assistance of directing groups and relies on a synergistic catalytic cycle in which phosphine-ligated silver complexes cleave the aryl C-H bond, while palladium catalysts enable the formation of the biaryl products. Mechanistic experiments, including kinetic isotope effects, competition experiments, and hydrogen-deuterium exchange, support a catalytic cycle in which cleavage of the C-H bond by silver is the rate-determining step.

The Effect of Freeze-Drying Pretreatment on the Accuracy of Near Infrared Spectroscopic Food Analysis to Predict the Nutritive Values of Japanese Cooked Foods.

The official testing methods for establishing nutritive values are accurate but relatively costly and time-consuming. Near infrared spectroscopy (NIRS) is potentially an alternative method that can analyze several components in a few minutes using an exclusively electronic instrument with no need for a laboratory expert. However, the accuracy of commercial NIRS spectroscopic food analyzers is not sufficient for Japanese food labeling, because of interference from moisture contained in the foods. This study aims to assess the effect of a freeze-drying pretreatment on the accuracy of NIRS food analysis. Thirty-four samples, consisting of six food items habitually consumed in Japan and cooked by different cooking methods were treated by milling then freeze-drying. They were analyzed by a commercial NIRS instrument (Calorie AnswerTM) with calibration curves developed based on other freeze-dried samples. The obtained nutritive values (energy, protein, lipid, carbohydrate and moisture) were corrected to the values before freeze-drying using the vaporized moisture content. The same samples before freeze-drying were also analyzed using the official testing methods to assess the analytical accuracy using NIRS after freeze-drying, and further analyzed using the same NIRS with the commercial calibration curves to assess the effect of freeze-drying. The accuracies were better for the freeze-dried samples than for the wet samples. The magnitude of the error in energy and carbohydrate was significantly associated with the retained moisture content in the freeze-dried sample. In conclusion, freeze-drying was an effective pretreatment for improving the accuracy of NIRS analyses of Japanese cooked foods, although it is still time-consuming and needs additional investment.

Observation of Microstructure Formation During Freeze-Drying of Dextrin Solution by in-situ X-ray Computed Tomography.

In-situ X-ray computed tomography (CT) was used to observe microstructure formations during freeze-drying of a dextrin solution. A specially designed freeze-drying stage was equipped at the X-ray CT stage. Frozen and dried microstructures were successfully observed. The CT images of the frozen solution clarified the ice crystal size increase and obvious boundary formation between the ice and freeze-concentrated phases upon performing post-freezing annealing at -5°C. These structural modifications emerged owing to Ostwald ripening and glassy phase relaxation. During the freeze-drying, pore microstructures formed as a consequence of water removal. The pores were replicas of the original ice microstructures; some pore microstructures newly formed by the removal of water. The latter mechanism was more obvious in the non-annealed sample than in the annealed sample. The glassy phase in the non-annealed solution was not perfectly freeze-concentrated; water was rapidly removed from this phase, losing its original microstructure. At this moment, the freeze-concentrated region piled up to new pore walls, which consequently thickened the pore walls. An image analysis estimated that the mean pore wall thicknesses for the non-annealed and annealed samples were 13.5 and 8.6 µm, respectively. It was suggested that the advantages of annealing are not only to reduce drying time owing to the modification of ice crystal morphologies but also to avoid quality loss related to the structural deformation of the glassy matters.

Primary mucosa-associated lymphoid tissue (MALT) lymphoma arising from the male urethra. A case report and review of the literature.

Primary non-Hodgkin's lymphomas rarely arise from the lower urinary tract, the urethra being the most uncommon site of origin. Herein, we report the immunohistochemical findings of a case of primary marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising from the male urethra. To clarify the clinicopathological findings of primary urethral lymphoma, we reviewed 14 previously reported cases. A 56-year-old man presented with gross hematuria. Cystourethroscopy demonstrated a nodular bulge of the urethral wall. Histologically, a transurethral biopsy specimen showed a dense lymphoplasmacytoid infiltrate in the urethral mucosa. The tumor cells were composed of centrocyte-like cells, plasma cells and plasmacytoid cells. A few plasma cells contained intracytoplasmic pseudoinclusions (Dutcher bodies). Immunohistochemical study revealed monotypic intracytoplasmic kappa-light chain in the plasma cells and plasmacytoid cells. The patient received a total of 50 Gy extrabeam irradiation. Follow-up 21 months later did not disclose any sign of local or other recurrences.