ortho-Quinone methides, arising from a formal [2+2] cycloaddition between arynes and DMF, were found to facilely undergo a [4+2] cycloaddition with ester enolates or ketenimine anions to produce diverse coumarins in a straightforward manner.

Betanodaviruses, the causative agents of viral nervous necrosis in marine fish, have bipartite positive-sense RNA genomes. The viruses have been classified into 4 distinct types based on nucleotide sequence similarities in the variable region (the so-called T4 region) of the smaller genomic segment RNA2 (1.4 kb). Betanodaviruses have marked host specificity, although the primary structures of the viral RNAs and encoded proteins are similar among the viruses. We have previously demonstrated, using reassortants between striped jack nervous necrosis virus (SJNNV) and redspotted grouper nervous necrosis virus (RGNNV), that RNA2, which encodes the coat protein, strictly controls host specificity. However, because RNA2 is large, we were unable to propose a mechanism underlying this RNA2-based host specificity. To identify the RNA2 region that controls host specificity, we constructed RNA2 chimeric viruses from SJNNV and RGNNV and tested their infectivity in the original host fish, striped jack Pseudocaranx dentex and sevenband grouper Epinephelus septemfasciatus. Among these chimeric viruses, SJNNV mutants containing the variable region of RGNNV RNA2 infected sevenband grouper larvae in a manner similar to RGNNV, while RGNNV mutants containing the variable region of SJNNV RNA2 infected striped jack larvae in a manner similar to SJNNV. Immunofluorescence microscopic studies using anti-SJNNV polyclonal antibodies revealed that these chimeric viruses multiplied in the brains, spinal cords and retinas of the infected fish, as in infections by the parental viruses. These results indicate that the variable region of RNA2 is sufficient to control host specificity in SJNNV and RGNNV.

Magic trio: Arynes are easily coupled with neutral nucleophiles and organic bromides to afford functionalized bromoarenes depending upon the nucleophile (Nu). The three‐component coupling proceeds through the formation of bromine ate complexes, and can be applied to the synthesis of multisubstituted isoquinolines and benzo[b]oxepines having pharmacological activity.

Background The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear. Methods The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition. Results In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p < 0.001). Side effects occurred after the second dose in 571 female (92.1%) and 178 male participants (80.1%). Female participants had a higher incidence of side effects than the male participants (p < 0.001). A comparison among the age groups showed significant differences (p = 0.018), and the frequency of side effects decreased with age. Twenty-three individuals participated in the survey of antibody titer transition. After the second vaccine dose, the median antibody titers for IgG and IgM were 3.76 and 0.07 AU/mL, respectively. Both IgG and IgM titers showed a significant increase over the study period (p < 0.001). Conclusions The BNT162b2 mRNA COVID-19 vaccine might be safe for Japanese people, and the antibody titer increased with two doses of vaccination. Larger nationwide studies are warranted to verify these findings.

Background Coronavirus disease 2019 (COVID-19) has spread worldwide and is also an important disease in Japan. Thus, the optimal treatment strategy for severe COVID-19 should be established urgently. The effects of combination treatment with baricitinib—a Janus kinase inhibitor, remdesivir, and dexamethasone (BRD) are unknown. Methods Patients who received combination therapy with BRD at the Japanese Red Cross Medical Center were enrolled in the study. All patients received baricitinib (≤14 d), remdesivir (≤10 d), and dexamethasone (≤10 d). The efficacy and adverse events were evaluated. Results In total, 44 patients with severe COVID-19 were enrolled in this study. The 28-d mortality rate was low at 2.3 % (1/44 patients). The need for invasive mechanical ventilation was avoided in most patients (90 %, 17/19 patients). Patients who received BRD therapy had a median hospitalization duration of 11 d, time to recovery of 9 d, duration of intensive care unit stay of 6 d, duration of invasive mechanical ventilation of 5 d, and duration of supplemental oxygen therapy of 5 d. Adverse events occurred in 15 patients (34 %). Liver dysfunction, thrombosis, iliopsoas hematoma, renal dysfunction, ventilator-associated pneumonia, infective endocarditis, and herpes zoster occurred in 11 %, 11 %, 2 %, 2 %, 2 %, 2 %, and 2 % of patients, respectively. Conclusions Combination therapy with BRD was effective in treating severe COVID-19, and the incidence rate of adverse events was low. The results of the present study are encouraging; however, further randomized clinical studies are needed.

A direct method for the synthesis of acridane derivatives based upon a 2:1 coupling reaction between arynes and imines was developed. The reaction proceeds through formation of transient aza‐ortho‐quinone methides arising from a net [2+2] cycloaddition between arynes and imines. Introduction of steric bulk into an imine carbon has proven to be vital for this facile coupling.

Trifluoromethyl ketones were found to be coupled with arynes in three modes depending upon their substitution patterns, namely C-C bond cleavage, [2+2] cycloaddition and O-arylation.

Silylstannylation of alkynes and allenes has been found to proceed by three-component coupling using a silylborane and a tin alkoxide in the presence of a Cu(I) catalyst. The regioselectivities are completely inverse to those of the conventional silylstannylation under palladium catalysis.