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2-Propynamides have been never used as substrates in classic and TfO-promoted Bischler-Napieralski reactions. In this article, a novel tandem synthesis of benzo[]acridines is developed from -aryl-2-propynamides and alkynes consisting of a TfO-promoted intermolecular Bischler-Napieralski reaction and a TfOH-promoted intramolecular Friedel-Crafts reaction.
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http://dx.doi.org/10.1021/acs.joc.1c02918 | DOI Listing |
Acc Chem Res
February 2025
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China.
ConspectusThe Mannich reaction, involving the nucleophilic addition of an enol(ate) intermediate to an imine or iminium ion, is one of the most widely used synthetic methods for the synthesis of β-amino carbonyl compounds. Nevertheless, the homo-Mannich reaction, which utilizes a homoenolate intermediate as the nucleophilic partner and provides straightforward access to the valuable γ-amino carbonyl compounds, remains underexplored. This can be largely attributed to the difficulties in generation and manipulation of the homoenolate species, despite various homoenolate equivalents that have been developed.
View Article and Find Full Text PDFBioorg Med Chem Lett
May 2024
Faculty of Science and Technology, Oita University, Dannoharu, Japan. Electronic address:
A novel series of benzo[6,7]indolo[3,4-c]isoquinolines 3a-3f was designed by scaffold hopping of topoisomerase I inhibitor benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-ones (BBPIs), which were developed by structural modification of the natural marine product lamellarin. The unconventional pentacycle was constructed by Bischler-Napieralski-type condensation of amide 11 and subsequent intramolecular Heck reaction. In vitro anticancer activity of the synthesized benzo[6,7]indolo[3,4-c]isoquinolines was evaluated on a panel of 39 human cancer cell lines (JFCR39).
View Article and Find Full Text PDFJACS Au
February 2024
Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
Visceral leishmaniasis and Chagas disease are neglected tropical diseases (NTDs) that severely impact the developing world. With current therapies suffering from poor efficacy and safety profiles as well as emerging resistance, new drug leads are direly needed. In this work, 26 alkaloids (9 natural and 17 synthetic) belonging to the benzyltetrahydroisoquinoline (BI) family were evaluated against both the pro/trypomastigote and amastigote forms of the parasites and , the causative agents of these diseases.
View Article and Find Full Text PDFNat Prod Res
July 2025
Directorate of Drug Substance Development, Egis Pharmaceuticals PLC, Budapest, Hungary.
Orthoscuticellines A and B are newly isolated natural -carboline alkaloids from the moss animal . Herein, we report the first targeted total synthesis of orthoscuticelline B and an analogous synthetic method for the preparation of dihydro derivate of orthoscuticelline A. The new synthetic approach is based on commercially available and inexpensive reagents leading to a practical synthesis of the target molecules.
View Article and Find Full Text PDFChem Commun (Camb)
October 2023
School of Chemistry and Chemical Engineering Northwestern Polytechnical University, Xi'an, 710072, P. R. China.