Organocatalytic aromatization-promoted umpolung reaction of imines.

The umpolung functionalization of imines bears vast synthetic potential, but polarity inversion is less efficient compared with the carbonyl counterparts. Strong nucleophiles are often required to react with the N-electrophiles without catalytic and stereochemical control. Here we show an effective strategy to realize umpolung of imines promoted by organocatalytic aromatization. The attachment of strongly electron-withdrawing groups to imines could enhance the umpolung reactivity by both electronegativity and aromatic character, enabling the direct amination of (hetero)arenes with good efficiencies and stereoselectivities. Additionally, the application of chiral Brønsted acid catalyst furnishes (hetero)aryl C-N atropisomers or enantioenriched aliphatic amines via dearomative amination from N-electrophilic aromatic precursors. Control experiments and density functional theory calculations suggest an ionic mechanism for the umpolung reaction of imines. This disconnection expands the options to forge C-N bonds stereoselectively on (hetero)arenes, which represents an important synthetic pursuit, especially in medicinal chemistry.

Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Brønsted Acid-Catalyzed Isomerization of BCBs.

Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used in asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes are involved in enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- and enantiocontrol. The utilization of N-triflyl phosphoramide as a chiral Brønsted acid promoter enables this isomerization process to proceed under mild conditions with low catalyst loading as well as good functional group compatibility. The resulting chiral cyclobutenes could serve as platform molecules for downstream manipulations with excellent reservation of stereochemical integrity, demonstrating the synthetic practicality of the developed method. Control experiments have also been performed to verify the formation of a key carbocation intermediate at the benzylic position.

Overexpression of Lin28B Promoted the Proliferation of Adenomyotic Smooth Muscle Cells of the Junctional Zone via Regulating Let-7a.

The inner myometrium, also called the junctional zone (JZ), is believed to play a major role in the development of adenomyosis. Recently, we found that the lethal-7a (Let-7a) microRNA (miRNA) was clearly downregulated in the miRNA expression profiles of JZ smooth muscle cells (JZSMCs) of patients with adenomyosis. Lin28, including Lin28A and Lin28B, is responsible for the post-transcriptional downregulation of the Let-7 miRNA family. However, the expression pattern of Lin28 and the function of the Lin28/Let-7 axis in adenomyosis have not yet been identified. In this study, we aim to explore the potential roles of the Lin28/Let-7 axis in the development of adenomyosis. Immunohistochemistry, western blot, and reverse transcription polymerase chain reaction (RT-qPCR) were used to evaluate the Lin28 expression, respectively. The correlation between Let-7a, Lin28A, and Lin28B expression was further examined using Pearson's correlation analysis. RNA interference was used to inhibit Lin28B gene, and then Cell Counting Kit (CCK-8) assay was performed to detect the cell proliferation capacity. The results revealed that the expression levels of Lin28B were upregulated in the JZ of adenomyosis whatever about proteins or mRNA (P < 0.0001); furthermore, its mRNA expression level was negatively correlated with Let-7a (r = - 0.749, P < 0.0001). After inhibiting Lin28B gene, the proliferation capacity of JZSMCs in adenomyosis group decreased after 48 h (P < 0.05). These results indicated that Lin28B may be involved in the pathogenesis of adenomyosis by promoting the proliferation capacity of JZSMCs via regulating Let-7a.

Expression of Cannabinoid Receptors in Myometrium and its Correlation With Dysmenorrhea in Adenomyosis.

The myometrium, especially the junctional zone (JZ), is now well documented to have a role in the pathogenesis of adenomyosis. Cannabinoid receptors have been shown to participate in the establishment of endometriosis and its pain perception. However, its relation to adenomyosis has not been identified yet. The aim of this study was to investigate the expression of cannabinoid receptor type I (CB1) and type II (CB2) in myometrium of uteri with and without adenomyosis and determine the correlation between their levels and clinical parameters of adenomyosis. We collected tissue samples of JZ and the outer myometrium from 45 premenopausal women with adenomyosis and 34 women without adenomyosis. CB1 and CB2 messenger RNA (mRNA) and protein expression levels were evaluated by the use of Western blotting and real-time quantitative polymerase chain reaction from all samples. Clinical information on the severity of dysmenorrhea and other data were collected. We found both CB1 and CB2 mRNA and protein levels in women with adenomyosis were significantly higher than those of controls, and CB1 expression levels in JZ were positively correlated with the severity of dysmenorrhea. These data suggest that cannabinoid receptor CB1 may be involved in the pathogenesis of dysmenorrhea in adenomyosis and may be a potential therapeutic target.

[Cloning and expression of a fragment of Corylus heterophylla 1 and identifying its immunologic competence].

AIM: To clone, express, and identify a fragment of Cor h 1 from Corylus heterophylla. METHODS: Through bioinformatics predication, the antigenic epitope of Cor h 1 was selected. A fragment gene of Cor h 1 was amplified by PCR and cloned into pMD18-T vector for sequencing. Then the fragment gene was sub cloned into pET-32a expression vector for expression, and then purified by metal (Ni(2+);) chelating affinity chromatography. The immunogenicity was tested by Western blot. RESULTS: The length of the fragment gene was 243 bp, coding 81 amino acids; the relative molecular mass of recombinant protein was 9 000. And the fragment of Cor h 1 was mainly expressed as soluble protein, purified protein has good immunogenicity. CONCLUSION: The fragment gene of Cor h 1 was successfully cloned and expressed in this study, and the recombinant protein possessed good IgE-binding capacity.