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Analogs of pyrrole alkaloid lamellarins exhibit anticancer activity by modulating multiple cellular events. Lethal doses of several lamellarins were found to enhance autophagy flux in HeLa cells, suggesting that lamellarins may modulate protein homeostasis through the interference of proteins or kinases controlling energy and nutrient metabolism. To further delineate molecular mechanisms and their targets, our results herein show that azalamellarin D (AzaD) cytotoxicity could cause translational attenuation, as indicated by a change in eIF2α phosphorylation. Intriguingly, acute AzaD treatment promoted the phosphorylation of GCN2, a kinase that transduces the integrated stress response (ISR), and prolonged exposure to AzaD could increase the levels of the phosphorylated forms of eIF2α and the other ISR kinase protein kinase R (PKR). However, the effects of AzaD on ISR signalling were marginally abrogated in cells with genetic deletion of GCN2 and PKR, and evaluation of protein target engagement by cellular thermal shift assay (CETSA) revealed no significant interaction between AzaD and ISR kinases. Further investigation revealed that acute AzaD treatment negatively affected mechanistic target of rapamycin (mTOR) phosphorylation and signalling. The analyses by CETSA and computational modelling indicated that mTOR may be a possible protein target for AzaD. These findings indicate the potential for developing lamellarins as novel agents for cancer treatment. [ABSTRACT FROM AUTHOR]

This document discusses a copper-catalyzed oxa-Diels-Alder reaction that allows for the synthesis of functionalized isochromans, which are important in organic synthesis and have applications in natural products and pharmaceuticals. The authors used sultines as reactants, which undergo a reaction to generate reactive intermediates that can react with aldehydes and ketones. The presence of a copper catalyst suppresses unwanted byproducts and allows for the synthesis of a variety of substituted sultines and carbonyl compounds. The method is simple and provides good yields of functionalized isochromans. [Extracted from the article]

The resulting solution was evaporated under reduced pressure to give the crude product, which was further purified by column chromatography on silica gel (20% EtOAc/hexane) to furnish B 30 b (49.5 mg, 0.19 mmol, 58%) as a white solid; mp 107.4-107.7 °C. The resulting solution was evaporated under reduced pressure to give the crude product B 29 b , which was further purified by column chromatography on silica gel (20% EtOAc/hexane) to furnish B 29 b (10.5 mg, 0.04 mmol, 75%) as a clear sticky oil. Keywords: epoxidation; cyclization; carbocation; fused-ring systems; stereoselectivity EN epoxidation cyclization carbocation fused-ring systems stereoselectivity 2757 2772 16 08/17/23 20230901 NES 230901 Graph Various oxacycles are privileged scaffolds in pharmaceutical industries, cosmetics, natural products, and drug discovery, among others. TOF-HRMS: I m i / I z i [M + Na] SP + sp calcd for C SB 19 sb H SB 20 sb O SB 4 sb Na: 335.1254; found: 335.1247. tert -Butyldimethyl((3-phenyl-1,3-dihydroisobenzofuran-1-yl)methoxy)silane (26b') By following the General Procedure G, and purification by column chromatography on silica gel (20% EtOAc/hexane), the product (24.0 mg, 0.71 mmol, 44%) was obtained as a yellow sticky gum. [Extracted from the article]

By starting from two simple building blocks, benzannulated cyclooctenones were obtained in three steps. Subsequent Grignard/aryl lithium addition to the ketone yielded the corresponding tertiary alcohols that underwent stereoselective acid-catalyzed transannular cyclization to provide a cis -fused 5/5 bicyclic indanylindane framework exclusively. Subsequent stereoselective nucleophilic addition to the indanyl cation by hydride, water, or electron-rich aromatics furnished the 4b-aryltetrahydroindano[1,2- a ]indenes in good to excellent yields (up to 92%) in the trans -C9–C9a form in up to a >99:1 diastereomeric ratio. [ABSTRACT FROM AUTHOR]

Solid-supported acids are investigated for aromatic debenzylation reactions. Stoichiometric amounts of solid-supports acids in refluxing toluene with or without 4 equiv of methanol effectively provided the desired aromatic debenzylation products of various systems in moderate to excellent yields (up to 98%).

Four solid-supported reagents are utilized in the multistep synthesis of lamellarins. The use of polymer-supported reagents facilitates the synthesis by minimizing both the workgroup procedure and column chromatography, rendering synthetic approaches more practical.

2-Arylchromans are prepared from the hetero-Diels-Alder reactions of styrenes with the ortho-quinone methides (o-QMs), which are generated by treating the MOM-protected benzylacetate derivatives with p-TsOH immobilized on silica (PTS-Si) in toluene. The corresponding chromans are obtained in excellent yields and diastereoselectivity.

The synthesis of unsymmetrical 1,2-diarylethane-1,2-dione involving the intramolecular cyclization of anionic benzylic ester of the aryl benzyl ether followed by oxidation employing dioxirane is described. The method could also be used to synthesize unsymmetrical benzils and other biologically important oxygen heterocyclic compounds.