Ring-Opening Fluorination of Carbo/Heterocycles and Aromatics: Construction of Complex and Diverse Fluorine-Containing Molecules.

Fluorine-containing molecules have attracted much attention in medicinal, agrochemical, and materials sciences because they offer unique physical and biological properties. Therefore, many efficient fluorination reactions have been developed over the years. Recent advancements in fluorination chemistry have expanded the range of substrates, and regioselectivity/stereoselectivity control has also been achieved.

Ring-Opening Fluorination of Isoxazoles.

A ring-opening fluorination of isoxazoles has been developed. Upon treatment of isoxazoles with an electrophilic fluorinating agent (Selectfluor), fluorination followed by deprotonation leads to tertiary fluorinated carbonyl compounds. This method features mild reaction conditions, good functional group tolerance, and a simple experimental procedure.

Ring-opening fluorination of bicyclic azaarenes.

We have discovered a ring-opening fluorination of bicyclic azaarenes. Upon treatment of bicyclic azaarenes such as pyrazolo[1,5-]pyridines with electrophilic fluorinating agents, fluorination of the aromatic ring is followed by a ring-opening reaction. Although this overall transformation can be classified as an electrophilic fluorination of an aromatic ring, it is a novel type of fluorination that results in construction of tertiary carbon-fluorine bonds.

Pd-Catalyzed Asymmetric Dearomative Arylation of Indoles via a Desymmetrization Strategy.

Pd-catalyzed asymmetric dearomative arylation of C3-substituted indoles is realized via a desymmetrization strategy. A BINOL-derived chiral phosphoramidite ligand is found to be highly efficient for the stereoselective control in this reaction. This method provides a convenient synthesis of spiroindolenines bearing two stereogenic centers in good yields (up to 98%) with excellent diastereo- and enantioselectivities (up to >20:1 dr and 97% ee), which could also be applied in asymmetric dearomative arylation of the simple C3-tethered indoles.

Catalytic three-component C-C bond forming dearomatization of bromoarenes with malonates and diazo compounds.

A Pd-catalyzed dearomative three-component C-C bond formation of bromoarenes with diazo compounds and malonates was developed. Various bromoarenes ranging from benzenoids to azines and heteroles were transformed to the corresponding substituted alicyclic molecules. The key to this reaction is the generation of a benzyl-palladium intermediate, which reacts with malonates to form a Pd--enolate species.

Dearomative Allylation of Naphthyl Cyanohydrins by Palladium Catalysis: Catalyst-Enhanced Site Selectivity.

A dearomative allylation of naphthyl cyanohydrins with allyl borates and allyl stannanes under palladium catalysis was developed. At the initial stage of this study, the dearomative reaction (C4 substitution of the aromatics) was competing with benzyl substitution. To circumvent this issue, the use of palladium and -disubstituted triarylphosphine as the catalyst in a 1:1 ratio was found to enhance the site selectivity, furnishing the desired dearomatized products.

Pd-Catalyzed Dearomative Allylation of Benzyl Phosphates.

Dearomative C-C bond formation of benzyl phosphates has been developed. In the presence of a palladium/PAr catalyst, benzyl phosphates reacted with allyl borates to generate the allylated product in a dearomative fashion. The resulting dearomatized molecules were successfully derivatized by Simmons-Smith cyclopropanation and oxidation.

Molecular species of prostaglandins involved in modulating luteinising hormone pulses of female rats under infectious stress conditions.

Mammalian reproductive function is controlled by the hypothalamic-pituitary-gonadal (HPG) axis, which is suppressed under infectious stress conditions. By analysing the pulsatility of luteinising hormone (LH), we have previously demonstrated that prostaglandins (PGs) in the central nervous system mediate infectious stress to suppress the activity of the HPG axis. The present study aimed to characterise the types of PGs responsible for suppression of the HPG axis.

Free access to running wheels abolishes hyperphagia in human growth hormone transgenic rats.

Obesity is a major health problem, and increased food intake and decreased physical activity are considered as two major factors causing obesity. Previous studies show that voluntary exercise in a running wheel decreases not only body weight but also food intake of rats. We previously produced human growth hormone transgenic (TG) rats, which are characterized by severe hyperphagia and obesity.

Functional organization of preoptic vasotocin and isotocin neurons in the brain of rainbow trout: central and neurohypophysial projections of single neurons.

Preoptic magnocellular neurosecretory cells (NSCs) in the brain of rainbow trout show synchronization of periodic Ca(2+) pulses, patterns of which differ between vasotocin (VT) and isotocin (IT) neurons. To provide neuroanatomical bases of the synchronized periodic Ca(2+) pulses and their biological implications, we examined the organization of preoptic VT and IT neurons in the brain of rainbow trout. The cytoarchitecture of the preoptic neurosecretory system was characterized by a confocal double-color immunofluorescence.

[Refractory acute myelogenous leukemia successfully treated with a continuous infusion chemotherapy of low dose aclarubicin and cytosine arabinoside: a case report].

A 44-year-old female with refractory acute myelogeneous leukemia had experienced an early relapse after a third complete remission (CR) with combination chemotherapy (BHAC-AMP) using daily one-shot infusion of 20 mg aclarubicin (ACR). Further treatments including intermediate dose of cytosine arabinoside (Ara-C) were not effective. After treatment with a continuous administration of low dose ACR (9 mg/day) and Ara-C (21 mg/day) for 14 days she entered a fourth CR.

MDR1 (multidrug resistance) gene expression in adult acute leukemia: correlations with blast phenotype.

Resistance to multiple chemotherapeutic agents is related to the production of P-glycoprotein, a transmembrane drug efflux pump that is encoded by the multidrug resistance gene (MDR1). To detect low-level or heterogenous expression of the MDR1 gene in acute leukemia, we have developed sensitive, specific and semi-quantitative protocols for measuring levels of MDR1 mRNA, based on the polymerase chain reaction. Using this assay, we screened blasts from 20 patients with untreated adult acute leukemia for evidence of MDR1 gene expression.

Acquired chronic pure red cell aplasia successfully treated with intravenous pulse methylprednisolone therapy.

A 65-year-old male patient developed acquired chronic pure red cell aplasia (PRCA) associated with hypergammaglobulinemia and positive Coombs' test during the treatment of eosinophilic pneumonia with prednisolone (PSL). His PRCA was treated with oral PSL at a dose of 60 mg/day for 3 weeks, but anemia further progressed. Immediately after high-dose intravenous pulse methylprednisolone therapy (1 g/day for 3 days) however, reticulocyte crisis occurred and his anemia rapidly improved.

[Clinical study of miconazole on deep-seated fungal infections].

An investigation was made on the efficacy and the safety of miconazole (MCZ) in the treatment of deep seated mycosis. The drug was administered through intravenous drip infusion at dose levels of 800 to 2,000 mg/day to 21 cases of confirmed mycosis for which causative organisms was identified and to 32 cases to which other antibiotics considered to be appropriate had been administered at febrile stages but had failed to take effect, hence mycoses were strongly suspected. The overall clinical efficacy rate was 84.

Changes of lymphocyte subsets in leukemia patients who received allogenic bone marrow transplantation.

Proportional changes of lymphocyte subsets in the peripheral blood were monitored by two-color flow-cytometry in seven leukemia patients who had received allogenic bone marrow transplantation (BMT). Lymphocyte counts, and proportions of T and B-cells returned to normal ranges between the 2nd and 12th months after BMT. Activated T-cells prominently increased after BMT, and the values gradually returned toward normal.

[Clinical significance of gastrointestinal decontamination under protected environment].

Many infections are caused by the patient's own oro-intestinal microbial flora under a protected environment. Thirty-eight patients with acute leukemia and two patients with blast crisis of chronic myelocytic leukemia were treated under a protected environment with or without prophylactic antibiotics. Antibiotics used for decontamination were vancomycin (V), polymyxin B (P) and nystatin (N).

[Low-dose danazol therapy in idiopathic thrombocytopenic purpura].

Danazol was administered orally at a dosage of 50 mg/day to 17 patients (11 females and 6 males) with idiopathic thrombocytopenic purpura refractory to steroids and/or splenectomy. The patients had not been treated with conventional dosages of danazol. The drug was suspended in four patients because of adverse effects of danazol.

[Studies of intestinal microbial flora in the post-BMT (bone marrow transplantation) patients under a protected environment].

The changes of microbial burdens of six patients with leukemia (four patients with acute leukemia; two patients with chronic leukemia) were studied before and after bone marrow transplantation (BMT) under protected isolation. Oral nonabsorbable and topical antibodies were administered prophylactically to all patients. Under a protected environment, genus and species number of intestinal microbial flora were not so decreased in all patients who were treated with antibiotics, but no episodes of severe septicemia were detected due to intestinal microbial flora.

[Acute renal failure following dehydration and hemolytic crisis due to pneumonia in a case of PNH].

A 41-year-old female, who had been diagnosed as having paroxysmal nocturnal hemoglobinuria (PNH) in 1985, was admitted to our hospital with cough, fever, diarrhea, vomiting and palpitation in April 1988. The chest X-ray showed pneumonia in her right lung. In the peripheral blood, red blood cell count was 1.

B-cell malignant lymphoma associated with monoclonal macroglobulinemia and cryoglobulinemia.

A 55-year-old man was admitted to our hospital with fever, ascites, generalized lymphadenopathy and hepatosplenomegaly. A cervical lymph node was biopsied and diagnosed as a diffuse mixed cell type B-cell malignant lymphoma with positive cytoplasmic IgM in plasmacytoid lymphocytes and immunoblasts. Serum protein electrophoresis disclosed a monoclonal peak and immuno-electrophoresis identified the abnormal protein as IgM kappa(k).

Report of a case with chronic myelomonocytic leukemia: demonstration of leukemic monocytes lacking nonspecific esterase by flow cytometry using monoclonal antibodies.

Chronic myelomonocytic leukemia (CMML) is a rare leukemia, which is now included in myelodysplastic syndromes. In a small number of patients with CMML, problems in the diagnosis have been reported, especially when atypical morphological features in both monocytic and granulocytic cells due to dysmyelopoiesis are prominent, or when cytochemical characteristics are lost in the leukemic cells. The case history of a sixty-seven year-old male patient with CMML is described.