Herein, we report a nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes through reductive decarboxylation of redox-active esters. The present reaction enables the ...preparation of functionalized
-difluoroalkenes with the formation of sterically hindered C(sp
)-C(sp
) bonds under very mild reaction conditions, while tolerating many sensitive functional groups and requiring minimal substrate protection. Therefore, this method provides an efficient and convenient approach for late-stage modification of biologically interesting molecules.
We report a three-component olefin reductive dicarbofunctionalization for constructing alkylborates, specifically, nickel-catalyzed reductive dialkylation and alkylarylation of vinyl boronates with a ...variety of alkyl bromides and aryl iodides. This reaction exhibits good coupling efficiency and excellent functional group compatibility, providing convenient access to the late-stage modification of complex natural products and drug molecules. Combined with alkylborate transformations, this reaction could also find applications in the modular and convergent synthesis of complex compounds.
Nickel-catalyzed three-component olefin reductive dicarbofunctionalization for constructing alkylborates was achieved.
The application of Suzuki–Miyaura coupling reaction to forge the atropisomeric biaryls has seen remarkable progress but exploration of this chemistry to directly forge chiral C(aryl)‐C(alkene) axis ...is underdeveloped. The replacement of arene substrates by alkenes intensifies the challenges in terms of reactivity, configurational atropostability of product and selectivity control. By meticulous ligand design and fine‐tuning of reaction parameters, we identified a highly active 3,3′‐triphenylsilyl‐substituted phosphite ligand to realize arene‐alkene Suzuki–Miyaura coupling of hindered aryl halides and vinyl boronates under very mild conditions. The axially chiral acyclic aryl‐alkenes were generated in commendable efficiency, enantioselectivity and E/Z selectivity.
The construction of axially chiral acyclic aryl‐alkene skeletons via classic Suzuki–Miyaura reaction has been challenging compared to the biaryls. Rational optimization established an enabling 3,3′‐triphenylsilyl‐substituted phosphite ligand for asymmetric coupling of hindered aryl halides and vinyl boronates under mild conditions, affording the acyclic aryl‐alkenes in good yield, atroposelectivity and E/Z selectivity.
Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2‐rich nature imposes inherent obstruction to introduce stereogenic ...element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone‐derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long‐range chirality control. The enantioenriched anthrones could be elaborated into dibenzo‐fused seven‐membered N‐heterocycles containing well‐defined stereogenic center via Beckmann rearrangement with axial‐to‐point chirality conversion.
By a simple stereoselective condensation with remote chirality control, axial chirality could be introduced to the symmetric anthrone backbones that comprise mostly sp2‐hybridized carbons. The generated oxime ether functionality enables their transformation with axial‐to‐point chirality conversion via Beckmann rearrangement into enantioenriched dibenzo‐fused seven‐membered N‐heterocycles.
Rhabdomyosarcoma (RMS) is a prevalent form of soft tissue sarcoma that primarily affects children. Pediatric RMS is characterized by two distinct histological variants: embryonal (ERMS) and alveolar ...(ARMS). ERMS is a malignant tumor with primitive characteristics resembling the phenotypic and biological features of embryonic skeletal muscles. With the widespread and growing application of advanced molecular biological technologies, such as next-generation sequencing (NGS), it has been possible to determine the oncogenic activation alterations of many tumors. Specifically for soft tissue sarcomas, the determination of tyrosine kinase gene and protein related changes can be used as diagnostic aids and may be used as predictive markers for targeted tyrosine kinase inhibition therapy. Our study reports a rare and exceptional case of an 11-year-old patient diagnosed with ERMS, who tested positive for MEF2D-NTRK1 fusion. The case report presents a comprehensive overview of the clinical, radiographic, histopathological, immunohistochemical, and genetic characteristics of a palpebral ERMS. Furthermore, this study sheds light on an uncommon occurrence of NTRK1 fusion-positive ERMS, which may provide theoretical basis for therapy and prognosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial lung disease with a prognosis worse than lung cancer. It is a fatal lung disease with largely unknown ...etiology and pathogenesis, and no effective therapeutic drugs render its treatment largely unsuccessful. With continuous in-depth research efforts, the epigenetic mechanisms in IPF pathogenesis have been further discovered and concerned. As a widely studied mechanism of epigenetic modification, DNA methylation is primarily facilitated by DNA methyltransferases (DNMTs), resulting in the addition of a methyl group to the fifth carbon position of the cytosine base, leading to the formation of 5-methylcytosine (5-mC). Dysregulation of DNA methylation is intricately associated with the advancement of respiratory disorders. Recently, the role of DNA methylation in IPF pathogenesis has also received considerable attention. DNA methylation patterns include methylation modification and demethylation modification and regulate a range of essential biological functions through gene expression regulation. The Ten-Eleven-Translocation (TET) family of DNA dioxygenases is crucial in facilitating active DNA demethylation through the enzymatic conversion of the modified genomic base 5-mC to 5-hydroxymethylcytosine (5-hmC). TET2, a member of TET proteins, is involved in lung inflammation, and its protein expression is downregulated in the lungs and alveolar epithelial type II cells of IPF patients. This review summarizes the current knowledge of pathologic features and DNA methylation mechanisms of pulmonary fibrosis, focusing on the critical roles of abnormal DNA methylation patterns, DNMTs, and TET proteins in impacting IPF pathogenesis. Researching DNA methylation will enchance comprehension of the fundamental mechanisms involved in IPF pathology and provide novel diagnostic biomarkers and therapeutic targets for pulmonary fibrosis based on the studies involving epigenetic mechanisms.Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible interstitial lung disease with a prognosis worse than lung cancer. It is a fatal lung disease with largely unknown etiology and pathogenesis, and no effective therapeutic drugs render its treatment largely unsuccessful. With continuous in-depth research efforts, the epigenetic mechanisms in IPF pathogenesis have been further discovered and concerned. As a widely studied mechanism of epigenetic modification, DNA methylation is primarily facilitated by DNA methyltransferases (DNMTs), resulting in the addition of a methyl group to the fifth carbon position of the cytosine base, leading to the formation of 5-methylcytosine (5-mC). Dysregulation of DNA methylation is intricately associated with the advancement of respiratory disorders. Recently, the role of DNA methylation in IPF pathogenesis has also received considerable attention. DNA methylation patterns include methylation modification and demethylation modification and regulate a range of essential biological functions through gene expression regulation. The Ten-Eleven-Translocation (TET) family of DNA dioxygenases is crucial in facilitating active DNA demethylation through the enzymatic conversion of the modified genomic base 5-mC to 5-hydroxymethylcytosine (5-hmC). TET2, a member of TET proteins, is involved in lung inflammation, and its protein expression is downregulated in the lungs and alveolar epithelial type II cells of IPF patients. This review summarizes the current knowledge of pathologic features and DNA methylation mechanisms of pulmonary fibrosis, focusing on the critical roles of abnormal DNA methylation patterns, DNMTs, and TET proteins in impacting IPF pathogenesis. Researching DNA methylation will enchance comprehension of the fundamental mechanisms involved in IPF pathology and provide novel diagnostic biomarkers and therapeutic targets for pulmonary fibrosis based on the studies involving epigenetic mechanisms.
Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2‐rich nature imposes inherent obstruction to introduce stereogenic ...element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone‐derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long‐range chirality control. The enantioenriched anthrones could be elaborated into dibenzo‐fused seven‐membered N‐heterocycles containing well‐defined stereogenic center via Beckmann rearrangement with axial‐to‐point chirality conversion.
By a simple stereoselective condensation with remote chirality control, axial chirality could be introduced to the symmetric anthrone backbones that comprise mostly sp2‐hybridized carbons. The generated oxime ether functionality enables their transformation with axial‐to‐point chirality conversion via Beckmann rearrangement into enantioenriched dibenzo‐fused seven‐membered N‐heterocycles.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown origin and the most common interstitial lung disease. However, therapeutic options for IPF are limited, and novel ...therapies are urgently needed. Histone deacetylases (HDACs) are enzymes that participate in balancing histone acetylation activity for chromatin remodeling and gene transcription regulation. Increasing evidence suggests that the HDAC family is linked to the development and progression of chronic fibrotic diseases, including IPF. This review aims to summarize available information on HDACs and related inhibitors and their potential applications in treating IPF. In the future, HDACs may serve as novel targets, which can aid in understanding the etiology of PF, and selective inhibition of single HDACs or disruption of HDAC genes may serve as a strategy for treating PF.Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disease of unknown origin and the most common interstitial lung disease. However, therapeutic options for IPF are limited, and novel therapies are urgently needed. Histone deacetylases (HDACs) are enzymes that participate in balancing histone acetylation activity for chromatin remodeling and gene transcription regulation. Increasing evidence suggests that the HDAC family is linked to the development and progression of chronic fibrotic diseases, including IPF. This review aims to summarize available information on HDACs and related inhibitors and their potential applications in treating IPF. In the future, HDACs may serve as novel targets, which can aid in understanding the etiology of PF, and selective inhibition of single HDACs or disruption of HDAC genes may serve as a strategy for treating PF.
The application of Suzuki–Miyaura coupling reaction to forge the atropisomeric biaryls has seen remarkable progress but exploration of this chemistry to directly forge chiral C(aryl)‐C(alkene) axis ...is underdeveloped. The replacement of arene substrates by alkenes intensifies the challenges in terms of reactivity, configurational atropostability of product and selectivity control. By meticulous ligand design and fine‐tuning of reaction parameters, we identified a highly active 3,3′‐triphenylsilyl‐substituted phosphite ligand to realize arene‐alkene Suzuki–Miyaura coupling of hindered aryl halides and vinyl boronates under very mild conditions. The axially chiral acyclic aryl‐alkenes were generated in commendable efficiency, enantioselectivity and E/Z selectivity.
The construction of axially chiral acyclic aryl‐alkene skeletons via classic Suzuki–Miyaura reaction has been challenging compared to the biaryls. Rational optimization established an enabling 3,3′‐triphenylsilyl‐substituted phosphite ligand for asymmetric coupling of hindered aryl halides and vinyl boronates under mild conditions, affording the acyclic aryl‐alkenes in good yield, atroposelectivity and E/Z selectivity.
PDF
