Versatile Biaryls and Fused Aromatics through Oxidative Coupling of Hydroquinones with (Hetero)Arenes

Aijima T., Ueda R., Nakane T., et al. Versatile Biaryls and Fused Aromatics through Oxidative Coupling of Hydroquinones with (Hetero)Arenes. ChemistrySelect 9, e202400647 (2024); https://doi.org/10.1002/slct.202400647.Hydroquinones bearing an electron-withdrawing group at the C2-position can effectively underwent oxidative coupling with (hetero)arenes (e. g., indoles, electron-rich benzene derivatives) in the presence of 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and FeCl3 to produce the corresponding biaryl products. In the present reactions, the DDQ-mediated oxidation of hydroquinone derivatives produce benzoquinone intermediate, which subsequently underwent FeCl3-catalyzed nucleophilic addition of (hetero)arenes to the α,β-unsaturated carbonyl moiety to give the biaryl product in a one-pot manner. Especially, the indole-based biaryl products were further converted into tetracyclic aromatics through DDQ-mediated oxidation followed by FeCl3-catalyzed intramolecular cyclization. Thiophene derivatives were also applicable to give the tetracyclic aromatics. Moreover, the photophysical properties of the indole- and thiophene-based tetracyclic aromatics in the solution and the solid states were investigated

Versatile Biaryls and Fused Aromatics through Oxidative Coupling of Hydroquinones with (Hetero)Arenes

Hydroquinones bearing an electron-withdrawing group at the C2-position effectively underwent oxidative coupling with indoles or arenes in the presence of 2,3-dichloro-5,6-dicyano p-benzoquinone (DDQ) and FeCl3 to give the corresponding biaryls. Indole-based products were further converted into tetracyclic aromatics using DDQ and FeCl3. Thiophene derivatives were also applicable to give the tetracyclic aromatics, possessing luminescent properties

Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors

Abstract Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting