Phosphine-Catalyzed (4 + 1) Annulation of <i>o</i>‑Hydroxyphenyl and <i>o</i>‑Aminophenyl Ketones with Allylic Carbonates: Syntheses and Transformations of 3‑Hydroxy-2,3-Disubstituted Dihydrobenzofurans and Indolines

A phosphine-catalyzed (4 + 1) annulation reaction of <i>o</i>-hydroxyphenyl and <i>o</i>-aminophenyl ketones with ester-modified allylic carbonates has been developed, providing a facile and efficient method to synthesize functionalized 2,3-disubstituted dihydrobenzofurans and indolines. Under mild conditions and in the catalysis of PPh₃ (20 mol %), the reactions of <i>o</i>-hydroxyphenyl or <i>o</i>-aminophenyl ketones readily furnish highly functionalized 3-hydroxy-2,3-disubstituted dihydrobenzofurans or 3-hydroxy-2,3-disubstituted indolines in 40–99% yields with generally high diastereoselectivity. To further expand the utility of this annulation reaction to the synthesis of functionalized benzofurans and indoles, the CuSO₄-promoted chemical transformations of the annulation products have also been studied

Phosphine-Catalyzed (4 + 1) Annulation of <i>o</i>‑Hydroxyphenyl and <i>o</i>‑Aminophenyl Ketones with Allylic Carbonates: Syntheses and Transformations of 3‑Hydroxy-2,3-Disubstituted Dihydrobenzofurans and Indolines

A phosphine-catalyzed (4 + 1) annulation reaction of <i>o</i>-hydroxyphenyl and <i>o</i>-aminophenyl ketones with ester-modified allylic carbonates has been developed, providing a facile and efficient method to synthesize functionalized 2,3-disubstituted dihydrobenzofurans and indolines. Under mild conditions and in the catalysis of PPh₃ (20 mol %), the reactions of <i>o</i>-hydroxyphenyl or <i>o</i>-aminophenyl ketones readily furnish highly functionalized 3-hydroxy-2,3-disubstituted dihydrobenzofurans or 3-hydroxy-2,3-disubstituted indolines in 40–99% yields with generally high diastereoselectivity. To further expand the utility of this annulation reaction to the synthesis of functionalized benzofurans and indoles, the CuSO₄-promoted chemical transformations of the annulation products have also been studied

Approaching Piezoelectric Response of Pb-Piezoelectrics in Hydrothermally Synthesized Bi_0.5(Na_1–<i>x</i>K_<i>x</i>)_0.5TiO₃ Nanotubes

A large piezoelectric coefficient of 76 pm/V along the diameter direction, approaching that of lead-based piezoelectrics, is observed in hydrothermally synthesized Pb-free Bi_0.5(Na_0.8K_0.2)_0.5TiO₃ nanotubes. The 30–50 nm diameter nanotubes are formed through a scrolling and wrapping mechanism without the need of a surfactant or template. A molar ratio of KOH/NaOH = 0.5 for the mineralizers yields the Na/K ratio of ∼0.8:0.2, corresponding to an orthorhombic–tetragonal (O–T) phase boundary composition. X-ray diffraction patterns along with transmission electron microscopy analysis ascertain the coexistence of orthorhombic and tetragonal phases with (110) and (001) orientations along the nanotube length direction, respectively. ²³Na NMR spectroscopy confirms the higher degree of disorder in Bi_0.5(Na_1–<i>x</i>K_<i>x</i>)_0.5TiO₃ nanotubes with O–T phase coexistence. These findings present a significant advance toward the application of Pb-free piezoelectric materials

Detection of HI antibody titer and serum IgG, IgG₁, IgG_2a of antigen sparing.

<p>(A) HI antibody titer against different doses of V antigen after vaccination of V 0.05 μg, V 0.1μg, and V 0.5 μg mixed with 300 μg of AEAR on day 21 after first vaccination. (B) Detection of IgG titer in serum by indirect ELISA on day 7 after first immunization. (C) IgG titer in serum on day 7 and 14 after first immunization. (D) Detection of antibody IgG, IgG₁, IgG_2a in serum on day 14 and 21 after first immunization. Data were expressed as means SE (n = 6). The results were representatives of three independent experiments. * <i>P</i><0.05, ** <i>P</i><0.01, ns <i>P</i>>0.05.</p

Splenic lymphocyte proliferation assay.

<p><i>In vitro</i> spleen lymphocyte proliferation assays from mice treated with AEAR 300μg combined with different doses respectively on day 21 after first vaccination. Data were expressed as means±SE (n = 6). The results were representatives of three independent experiments. * <i>P</i><0.05, ** <i>P</i><0.01, ^ns <i>P</i>>0.05.</p

Analysis of DCs maturation and the expression of Tregs by FACS.

<p>Total splenocytes were isolated from the spleens of ICR mice on day 3 or 21 after first vaccination.(A-E) Double staining for CD11c⁺CD40⁺), CD11c⁺CD80⁺, CD11c⁺CD86⁺ and CD11c⁺MHC-II⁺ was performed. The percentages of CD11c⁺CD40⁺, CD11c⁺CD80⁺, CD11c⁺ CD86⁺, and CD11c⁺ MHC-II⁺ cells in the total cells are shown in (A), (B), (C) and (D) respectively. E) Treg expressions were analyzed by FACS. Splenocytes were isolated from ICR mice on day 3 after The expressions of CD4⁺CD25⁺Foxp3⁺cells were determined by FACS (I-J). Data were expressed as means±SE (n = 6). The results were representatives of three independent experiments.* <i>P</i><0.05, ** <i>P</i><0.01, ^ns <i>P</i>>0.05.</p

Detection of the percentages of T lymphocyte subsets by FACS.

<p>The lymphocyte subpopulation of CD3⁺CD4⁺(A-B), CD3⁺CD8⁺ T cells(C-D), CD4⁺CD44⁺ T cells (E-F), and CD8⁺CD44⁺ T cells(G-H) by FACS. The spleen lymphocytes were collected on day 21 after first vaccination from the mice immunized with AEAR and the different doses of V for detecting T lymphocyte subsets. Data were expressed as means±SE (n = 6). The results were representatives of three independent experiments. * <i>P</i><0.05, ** <i>P</i><0.01, ^ns <i>P</i>>0.05.</p

Detection of HI antibody titer and serum IgG antibody.

<p>(A) The titer of HI antibody against V antigen on day 21 after first vaccination with 0.5 μg V mixed with 100 μg, 300 μg, and 500 μg AEAR adjuvants respectively. (B) Detection of IgG by indirect ELISA in serum on day 14 and 21 after first vaccination. Data were expressed as means±SE (n = 6). The results were representatives of three independent experiments. * <i>P</i><0.05, ^ns <i>P</i>>0.05.</p

The group of immunization of antigen sparing.

<p>The group of immunization of antigen sparing.</p

Analysis of CD4⁺CD44⁺ T cells and CD8⁺CD44⁺ T cells.

<p>Mice in the AEAR treatment groups had an increased proportion of CD44⁺CD4⁺ T cells (A-B) and CD44⁺CD8⁺ T cells (C-D) in spleen compared with the V group measured by FACS. Data were expressed as means±SE (n = 6). The results were representatives of three independent experiments. * <i>P</i><0.05, ** <i>P</i><0.01, ^ns <i>P</i>>0.05.</p