An intramolecular palladium(0)-mediated α-arylation of ketones applied to the synthesis of various substituted tetracyclic indoles is reported. Most significantly, the efficiency of the transformation was enhanced by the use of monoligated Pd(0) complexes. This methodology was extended to double α-arylation of ketones using one-pot reactions with either simultaneous addition or sequential addition of two aryl halides for producing aryl substituted tetracyclic indoles.
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http://dx.doi.org/10.1021/jo300052z | DOI Listing |
Molecules
December 2024
Institut für Pharmazeutische und Medizinische Chemie, Universität Münster, Corrensstraße 48, D-48149 Münster, Germany.
J Org Chem
January 2025
Chang-Kung Chuang Institute, Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.
A new stereoselective [4+2] annulation method for constructing tetracyclic indolines by reacting indoles with bicyclic N-substituted cyclobutanes has been developed. Using Sc(OTf) as a catalyst, a series of tetracyclic indolines with four continued stereogenic carbon centers have been obtained in ≤86% yields as single diastereomers. This reaction offers an accessible way for the rapid construction of the core structures of biologically active natural products like paucidirinine, deethylibophyllidine, and ibophyllidine.
View Article and Find Full Text PDFJ Nat Med
January 2025
Faculty of Pharmaceutical Sciences, Hoshi University, Ebara 2-4-41 Shinagawa-ku, Tokyo, 142-8501, Japan.
Four new bisindole alkaloids, cathagines A (1)-D (4) consisting of an aspidosperma and the fused tetracyclic 3-spirooxindole derived from an iboga type skeleton were isolated from the whole plant of Catharanthus roseus. The structures including absolute stereochemistry were elucidated on the basis of 2D NMR data and CD spectra. Cathagine B (2) showed moderate anti-malarial activity against Plasmodium falciparum 3D7.
View Article and Find Full Text PDFACS Chem Biol
November 2024
Institute of Molecular Biology and Biophysics, Department of Biology, ETH Zurich, Zurich 8093, Switzerland.
ABCG2 is a multidrug transporter that protects tissues from xenobiotics, affects drug pharmacokinetics, and contributes to multidrug resistance of cancer cells. Here, we present tetracyclic fumitremorgin C analog Ko143 derivatives, evaluate their modulation of purified ABCG2, and report four high-resolution cryo-EM structures and computational analyses to elucidate their interactions with ABCG2. We found that Ko143 derivatives that are based on a ring-opened scaffold no longer inhibit ABCG2-mediated transport activity.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Department of Organic Chemistry, Indian Institute of Science, Bangalore, 560012, India.
The umpolung of aldimines using N-heterocyclic carbenes (NHCs) is less explored compared to the established polarity reversal of aldehydes. Described herein is an NHC-catalyzed imine umpolung /6π-electrocyclization cascade, which leads to the atom- and pot-economic synthesis of biologically important dihydrochromeno indoles. For the first time, the nucleophilic aza-Breslow intermediates have been intercepted with unactivated alkynes.
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