The first phosphoric acid catalyzed direct arylation of 2‐naphthylamines with iminoquinones for the atroposelective synthesis of axially chiral biaryl amino alcohols has been developed. This reaction ...constitutes a highly functional‐group‐tolerant route for the rapid construction of enantioenriched axially chiral biaryl amino alcohols, and is a rare example of 2‐naphthylamines acting as nucleophiles in an organocatalytic enantioselective transformation. Furthermore, the products, which feature various halogen atoms, provide access to structurally diverse axially chiral amino alcohols through further transformations.
The phosphoric acid catalyzed direct arylation of 2‐naphthylamines with iminoquinones enables the atroposelective synthesis of axially chiral biaryl amino alcohols. Many functional groups are tolerated in this reaction, and it is a rare example of 2‐naphthylamines acting as nucleophiles in an organocatalytic enantioselective transformation.
Presented here is a class of novel axially chiral aryl‐p‐quinones as platform molecules for the preparation of non‐C2 symmetric biaryldiols. Two sets of aryl‐p‐quinone frameworks were synthesized ...with remarkable enantiocontrol by means of chiral phosphoric acid catalyzed enantioselective arylation of p‐quinones by central‐to‐axial chirality conversion. These aryl‐p‐quinones were then used to access a wide spectrum of highly functionalized non‐C2 symmetric biaryldiols with excellent retention of the enantiopurity.
A class of atropisomeric aryl‐p‐quinones were efficiently assembled by means of chiral phosphoric acid catalyzed enantioselective arylation of p‐quinones through a central‐to‐axial chirality transfer process. This novel axially chiral framework served as a platform for diversity‐oriented synthesis of a wide range of highly functionalized non‐C2 symmetric biaryldiols with preservation of the chirality.
The first phosphoric acid-catalyzed asymmetric direct arylative reactions of 2-naphthols with quinone derivatives have been developed, providing efficient access to a class of axially chiral ...biaryldiols in good yields with excellent enantioselectivities under mild reaction conditions. This approach is a highly convergent and functional group tolerant route to the rapid construction of axially chiral compounds from simple, readily available starting materials. The excellent stereocontrol of the process stems from efficient transfer of stereochemical information from the chiral phosphoric acid into the axis chirality of the biaryldiol products. Preliminary results demonstrate that the biaryldiols can act as efficient chiral ligands in asymmetric transformations.
Atropisomeric biaryl motifs are ubiquitous in chiral catalysts and ligands. Numerous efficient strategies have been developed for the synthesis of axially chiral biaryls. In contrast, the asymmetric ...construction of o-quinone-aryl atropisomers has yet to be realized. Inspired by the rapid progress of the chemistry of biaryls, here we present our initial investigations about the atroposelective construction of axially chiral arylquinones by a bifunctional chiral phosphoric acid-catalyzed asymmetric conjugate addition and central-to-axial chirality conversion. With o-naphthoquinone as both the electrophile and the oxidant, three types of arylation counterparts, namely 2-naphthylamines, 2-naphthols and indoles, are utilized to assemble a series of atropisomeric scaffolds in good yields and excellent enantioselectivities. This approach not only expands the axially chiral library but also offers a route to a class of potential, chiral biomimetic catalysts.
Structurally novel atropisomeric arylindole frameworks have been successfully constructed through chiral phosphoric acid-catalyzed asymmetric cross-coupling of indoles and quinone derivatives in a ...precise regioselective manner. This approach features high convergence and functional group tolerance to efficiently deliver diverse heteroaryl atropisomers with excellent enantiocontrol. The dominant formation of axial chirality but not central chirality, as the major unmet challenge for this type of reactions, was conquered by the rational and accurate modulation of the electronic and steric effects on both coupling partners. Preliminary investigation demonstrated the practicality of such axially chiral arylindoles as chiral ligands in asymmetric catalysis.
Testicular cancer is the most common solid malignancy among young men. We downloaded data of testicular cancer patients from The Cancer Genome Atlas database to find novel genes in the testicular ...cancer microenviroment based on ESTIMATE algorithm‐derived immune scores. A total of 156 cases of testicular cancer were included in this study and 165 cases of normal testicular tissues were used. We divided the testicular cancer patients into high‐ and low‐score groups based on their immune scores. We identified 1,226 differentially expressed genes (fold change > 2, false discovery rate < 0.05), including 688 downregulated genes and 538 upregulated genes, between these two groups. The top Gene Ontology terms were involved in the immune response‐regulating cell surface receptor signaling pathway, immune response‐activating cell surface receptor signaling pathway, external side of the plasma membrane, and receptor ligand activity. By performing the Kyoto Encyclopedia of Genes and Genomes analysis, we demonstrated that cAMP signaling pathway was highly enriched among these differentially expressed genes. High expression of LINC01564, LINC02208, ODAM, RNA5SP111, and RNU6‐196P were found to be associated with poor overall survival. The expression of genes was further validated by the Human Protein Atlas and only ALB and IFNG were demonstrated to be differentially expressed between testis tissue and testicular cancer tissue.
Testicular cancer is the most common solid malignancy among young men. We used the ESTIMATE algorithm to calculate immune scores and obtain several novel genes associated with testicular cancer microenvironment. Two genes were validated by the Human Protein Atlas database to be differentially expressed between testis tissue and testicular cancer tissues. These findings would contribute greatly to the understanding of the potential mechanism of testicular cancer.
Comprehensive Summary
Indole‐based atropisomers are a very important class of axially chiral compounds. However, the atroposelective synthesis of axially chiral 2‐arylindole remains largely ...unexplored. In this study, we report the successful synthesis of atropisomeric 2‐arylindoles using direct amination of indoles with p‐quinonediimines in the presence of chiral phosphoric acid as a catalyst. Quinonediimine acts as an aminating reagent through formal polarity inversion of imine. The malonate group on the 2‐aryl of 2‐indoles was found to be essential for high enantioselectivity of the products. This could be due to the additional interaction between the ester group and the catalyst, as well as the intramolecular hydrogen bonding. Our findings provide a new strategy for the asymmetric construction of 2‐arylindole atropisomers.
Herein, we developed a general and mild catalytic electrophilic amination of 2‐arylindoles with p‐quinone diimines to construct axially chiral 2‐arylindoles under mild conditions. With the proper choice of a chiral phosphoric acid and substituted 2‐arylindoles, the intermolecular C—N bond formation with various p‐quinonediimines proceeded with good yields and high stereoselectivities. This strategy provides a powerful method for enantioselective synthesis of 2‐arylindole atropisomers which successfully overcame the challenges in catalytic asymmetric construction of axially chiral five‐membered heterobiaryls.
Expression of kinesin family member 18B (KIF18B), an ATPase with key roles in cell division, is deregulated in many cancers, but its involvement in prostate cancer (PCa) is unclear. Here, we ...investigated the expression and function of KIF18B in human PCa specimens and cell lines using bioinformatics analyses, immunohistochemical and immunofluorescence microscopy, and RT-qPCR and western blot analyses. KIF18B was overexpressed in PCa specimens compared with paracancerous tissues and was associated with poorer disease-free survival. In vitro, KIF18B knockdown in PCa cell lines promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, while KIF18B overexpression had the opposite effects. In a mouse xenograft model, KIF18B overexpression accelerated and promoted the growth of PCa tumors. Bioinformatics analysis of control and KIF18B-overexpressing PCa cells showed that genes involved in the PI3K-AKT-mTOR signaling pathway were significantly enriched among the differentially expressed genes. Consistent with this observation, we found that KIF18B overexpression activates the PI3K-AKT-mTOR signaling pathway in PCa cells both in vitro and in vivo. Collectively, our results suggest that KIF18B plays a crucial role in PCa via activation of the PI3K-AKT-mTOR signaling pathway, and raise the possibility that KIF18B could have utility as a novel biomarker for PCa.
Lymph node metastasis is one of the most important independent risk factors that can negatively affect the prognosis of prostate cancer (PCa); however, the exact mechanisms have not been well ...studied. This study aims to better understand the underlying mechanism of lymph node metastasis in PCa by bioinformatics analysis. We analysed a total of 367 PCa cases from the cancer genome atlas database and performed weighted gene co‐expression network analysis to explore some modules related to lymph node metastasis. Gene Ontology analysis and pathway enrichment analysis were conducted for functional annotation, and a protein‐protein interaction network was built. Samples from the International Cancer Genomics Consortium database were used as a validation set. The turquoise module showed the most relevance with lymph node metastasis. Functional annotation showed that biological processes and pathways were mainly related to activation of the processes of cell cycle and mitosis. Four hub genes were selected: CKAP2L, CDCA8, ERCC6L and ARPC1A. Further validation showed that the four hub genes well‐distinguished tumour and normal tissues, and they were good biomarkers for lymph node metastasis of PCa. In conclusion, the identified hub genes facilitate our knowledge of the underlying molecular mechanism for lymph node metastasis of PCa.
Objectives. The incidence of hyperuricemia (HUA) is increasing year by year, and there are no ideal drugs for the treatment; the existing ones can cause serious liver and kidney damage. We have ...confirmed that the water extract of Dendrobium candidum leaves could reduce the level of uric acid in rats, but the active ingredients remain unknown, and the mechanism is not well understood. This research investigated the therapeutic effect of the macroporous resin extract of the Dendrobium candidum leaf (DLE) on hyperuricemia. In this study, hyperuricemia was induced in rats by a 5-week high-purine diet. After that, DLE was administered continuously for 9 weeks. The result showed that biochemical parameters of liver and kidney function, especially serum uric acid (UA) levels, were significantly improved with DLE, which may relate to the reduction of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the liver. Moreover, DLE could significantly prevent kidney and liver from damage, and intestinal injury and reduce inflammation in hyperuricemic rats by inhibiting the expression of both NF-κB and TLR4 proteins. These results showed that the macroporous resin extract of the Dendrobium candidum leaves may be effective for the treatment of hyperuricemia in rats by inhibiting uric acid production and decreasing inflammation.
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