Organocatalytic Enantioselective γ‑Aminoalkylation of Unsaturated Ester: Access to Pipecolic Acid Derivatives

The direct γ-carbon functionalization of α,β-unsaturated esters <i>via N</i>-Heterocyclic Carbene (NHC) catalysis is disclosed. This catalytically generated nucleophilic γ-carbon undergoes highly enantioselective additions to hydrazones. The resulting δ-lactam products can be readily transformed to optically enriched pipecolic acid derivatives

NHC-Catalyzed Chemo- and Enantioselective Reaction between Aldehydes and Enals for Access to Axially Chiral Arylaldehydes

A chiral carbene-catalyzed chemo- and enantioselective reaction with racemic biaryl aldehydes and α-bromoenals is developed for access to axially chiral 2-arylbenzaldehydes through atroposelective dynamic kinetic resolution (DKR) processes. This atroposelective DKR strategy can tolerate a broad scope of substrates with diverse functionalities. The axially chiral 2-aryl benzaldehyde products generally afford moderate to good yields and enantioselectivities. The axially chiral molecules afforded from the current approach are variable through simple transformations to afford axially chiral functional molecules with excellent optical purities

<i>N</i>‑Heterocyclic Carbene-Catalyzed Regio- and Enantioselective C7-Alkylation of 4‑Aminoindoles with α‑Bromoenals

The first carbene-catalyzed regio- and enantioselective indole C7-alkylation reaction between 4-aminoindoles and α-bromoenals is disclosed. The corresponding indole products could be obtained in moderate to good yields with good to excellent enantioselectivities. The evaluation of antibacterial activity against Psa revealed that nine of the C7-functionalized indoles exhibited superior inhibitory activities compared to the positive controls TC and BT. Our approach provides an efficient strategy to introduce a chiral chain into the C7 position of indole compounds, with potential applications evaluated in pesticide development

Enantioselective Intramolecular Formal [2 + 4] Annulation of Acrylates and α,β-Unsaturated Imines Catalyzed by Amino Acid Derived Phosphines

The first chiral phosphine-catalyzed activation of acrylates for intramolecular formal [2 + 4] reactions with unsaturated imines is described. The catalytic reactions afford <i>N</i>-heterocycles with exceptionally high diastereo- and enantioselectivities. The [2 + 4] products are amenable for further transformations to useful molecules such as chiral piperidines and multicyclic structures

Carbene-Catalyzed Indole 3‑Methyl C(sp³)–H Bond Functionalization

The metal-free catalytic functionalization of aromatic sp²-carbons and benzylic sp³-carbons remains challenging. Here we report a carbene-catalyzed functionalization of the 3-methyl sp³-carbon attached to 2-formyl-indoles. The reaction proceeds through an NHC-bound <i>o</i>-quinodimethane as the key intermediate generated from 2-formyl-3-methylindoles under oxidative conditions. Reactive ketones are found to be effective substrates to produce substituted hydropyrano­[3,4-<i>b</i>]­indoles in good to excellent yields

Carbene-Catalyzed Formal [5 + 5] Reaction for Coumarin Construction and Total Synthesis of Defucogilvocarcins

An N-heterocyclic carbene-catalyzed formal [5 + 5] reaction between enals and furanones that generates multisubstituted coumarins in a single step is reported. Five atoms in each of the substrates are involved in this catalytic process to form a benzene and a lactone ring. The power of the method is further demonstrated in metal-free total syntheses of several natural products (defucogilvocarcins M, E, and V) bearing coumarin as the key structural motif

Tat-Interacting Protein 30 (TIP30) Expression Serves as a New Biomarker for Tumor Prognosis: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Tat-interacting protein 30 (TIP30) is a tumor suppressor protein that has been found to be expressed in a wide variety of tumor tissues. TIP30 is involved in the control of cell apoptosis, growth, metastasis, angiogenesis, DNA repair, and tumor cell metabolism. The methylation of the TIP30 promoter is also associated with tumor prognosis. To evaluate this topic further, we conducted a systematic meta-analysis to explore the clinicopathological and prognostic significance of TIP30 for tumor patients.</p><p>Methods</p><p>We searched PubMed and EMBASE for eligible studies. We manually searched for printed journals and relevant textbooks. Subgroup analyses were performed based on the region, manuscript quality, methods of vasculogenic mimicry identification, pathology, and number of patients.</p><p>Results</p><p>Fourteen studies with 1705 patients were included in this meta-analysis. A significant association was observed between high expression of TIP30 in patients with cancer with a good overall survival (hazard ratio = 0.53, 95% confidence interval: 0.41–0.69), and good recurrence-free survival or disease free survival (hazard ratio = 0.49, 95% confidence interval: 0.37–0.66). Lack of expression of TIP30 had an association with lymph node metastasis (odds ratio = 3.90, 95% confidence interval: 2.21–6.89) and high tumor node metastasis clinical stage (odds ratio = 2.10, 95% confidence interval: 1.68–2.62). The methylation of the TIP30 promoter did not significantly influence the overall survival (hazard ratio = 0.99, 95% confidence interval: 0.88–1.13) or disease free survival (hazard ratio = 0.62, 95% confidence interval: 0.19–2.02).</p><p>Conclusions</p><p>TIP30 expression is associated with a good prognosis in patients with tumors. Clinical studies with large samples are needed worldwide and standardized protocols should be adopted in the future to achieve a better understanding of the relationship between tumor prognosis and TIP30.</p></div

Characteristics of the included studies.

<p>Characteristics of the included studies.</p

Quality assessment of the included studies.

<p>Quality assessment of the included studies.</p

Forest plot of hazard ratios (HRs) of OS in the random-effect model.

<p>The HR of overall survival time of TIP30 promoter methylated cancer patients was compared with TIP30 promoter unmethylated cancer patients. A HR = 0.99 implies no significant differences in OS for methylation of the TIP30 promoter.</p