A short and efficient synthetic strategy for the total syntheses of (S)-(+)-and (R)-(−)-plakolide A

Concise and efficient total syntheses of anticancer agents (S)-(+)-Plakolide A and (R)-(−)-Plakolide A were accomplished in eight steps and an overall yield of 39% starting from geraniol. The key steps in our strategy are Sharpless asymmetric epoxidation, double elimination, and Stille coupling reactions

Total syntheses of schulzeines B and C

Schulzeines B (2) and C (3) were synthesized by a convergent strategy using epimeric tricyclic lactam building blocks, 4 and 5, and the C28 fatty acid side chain 6. Syntheses of tricyclic lactams (4/5) were achieved by Bischler-Napieralski reaction. Sharpless asymmetric dihydroxylation and BINAL-H-mediated asymmetric reduction of an enone was employed to prepare the key fatty acid side chain 6. The spectral as well as analytical data of 2 and 3 were in good agreement with the reported data for the natural products, thus confirming their assigned structures

A New Solvent System (Cyclopentyl Methyl Ether–Water) in Process Development of Darifenacin HBr

Darifenacin is a potent and competitive M₃ selective receptor antagonist (M₃SRA), and its hydrobromide salt (<b>1</b>) is the active ingredient of pharmaceutical formulations for oral treatment of urinary incontinence. The present work demonstrates an efficient, commercial manufacturing process for darifenacin hydrobromide (<b>1</b>)

Efficient Synthesis of Impurity-C of Antimigraine Agent Rizatriptan Benzoate

During the commercial manufacturing of antimigraine drug Rizatriptan benzoate, several impurities are reported to be formed. This present work demonstrates a convergent and short synthesis of the most critical impurity (C) of Rizatriptan, [2-(5-((1H-1,2,4-triazol-1-yl)­methyl)-1H-indole-2-yl)-<i>N</i>,<i>N</i>-dimethylethanamine (<b>1</b>)], recently reported in U.S. Pharmacopeia

NSAID targets SIRT3 to trigger mitochondrial dysfunction and gastric cancer cell death

Summary: Gastric cancer (GC) is a deadly malignancy that demands effective therapeutic intervention capitalizing unique drug target/s. Here, we report that indomethacin, a cyclooxygenase non-selective non-steroidal anti-inflammatory drug, arrests GC cell growth by targeting mitochondrial deacetylase Sirtuin 3 (SIRT3). Interaction study revealed that indomethacin competitively inhibited SIRT3 by binding to nicotinamide adenine dinucleotide (NAD)-binding site. The Cancer Genome Atlas data meta-analysis indicated poor prognosis associated with high SIRT3 expression in GC. Further, transcriptome sequencing data of human gastric adenocarcinoma cells revealed that indomethacin treatment severely downregulated SIRT3. Indomethacin-induced SIRT3 downregulation augmented SOD2 and OGG1 acetylation, leading to mitochondrial redox dyshomeostasis, mtDNA damage, respiratory chain failure, bioenergetic crisis, mitochondrial fragmentation, and apoptosis via blocking the AMPK/PGC1α/SIRT3 axis. Indomethacin also downregulated SIRT3 regulators ERRα and PGC1α. Further, SIRT3 knockdown aggravated indomethacin-induced mitochondrial dysfunction as well as blocked cell-cycle progression to increase cell death. Thus, we reveal how indomethacin induces GC cell death by disrupting SIRT3 signaling

Process Development of Citalopram/Escitalopram Oxalate: Isolation and Synthesis of Novel Impurities

During process optimization of Escitalopram oxalate novel impurities, <b>6</b> and <b>7</b> were observed, which were isolated and characterized, and the proposed structure was confirmed by chemical synthesis. Investigation of the cause of impurities formation improved the yield and purity of the drug product during the bulk API synthesis

14-Membered Macrocyclic Ring-Derived Toolbox: The Identification of Small Molecule Inhibitors of Angiogenesis and Early Embryo Development in Zebrafish Assay

A highly practical and modular synthesis to obtain a diverse 14-membered ring-based macrocyclic toolbox is achieved. These compounds were further tested in zebrafish assays related to early embryonic development, angiogenesis, and neurogenesis, respectively. <b>1.4c</b> was identified as an antiangiogenesis agent

An Efficient, Scalable Process for Benzphetamine Hydrochloride

Commercial manufacturing of benzphetamine hydrochloride along with its impurity profiling is disclosed. Deoxygenation of pseudoephedrine is reported with ∼100% retention by shielding the amine group as its <i>tert</i>-butyl carbamate, which is very straightforward to eliminate at the end. Four unknown process-related impurities are isolated from the samples of final API and characterized on the basis of their NMR and mass spectral analysis. Structures of the isolated impurities are confirmed by independent syntheses and coinjecting with the isolated one