447 results match your criteria indoline derivatives


Synthesis and Preclinical Validation of Novel Indole Derivatives as a GPR17 Agonist for Glioblastoma Treatment.

J Med Chem 2021 Jul 25. Epub 2021 Jul 25.

Molecular Signaling Lab, Faculty of Medicine and Health Technology, Tampere University, 33720 Tampere, Finland.

The discovery of a potential ligand-targeting G protein-coupled receptor 17 (GPR17) is important for developing chemotherapeutic agents against glioblastoma multiforme (GBM). We used the integration of ligand- and structure-based cheminformatics and experimental approaches for identifying the potential GPR17 ligand for GBM treatment. Here, we identified a novel indoline-derived phenolic Mannich base as an activator of GPR17 using molecular docking of over 6000 indoline derivatives. Read More

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TFA-catalyzed Q-Tube Reactor-Assisted Strategy for the Synthesis of Pyrido[1,2-][1,2,4]triazine and Pyrido[1',2':2,3][1,2,4]triazino[5,6-]indole Derivatives.

ACS Omega 2021 Jun 8;6(24):16086-16099. Epub 2021 Jun 8.

Chemistry Department, Faculty of Science, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait.

An efficient high-pressure-assisted trifluoroacetic acid-catalyzed protocol for synthesizing unreported novel pyrido[1,2-][1,2,4]triazine and pyrido[1',2':2,3][1,2,4]triazino[5,6-]indole derivatives has been established. This strategy includes the condensation reactions of various 1-amino-2-imino-4-arylpyridine-3-carbonitrile derivatives with indoline-2,3-dione (isatin) derivatives and α-keto acids such as pyruvic acid and phenylglyoxylic acid. This strategy includes utilizing the Q-tube reactor as an efficient and safe tool to conduct these reactions under high-pressure conditions. Read More

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A Proline Mimetic for the Design of New Stable Secondary Structures: Solvent-Dependent Amide Bond Isomerization of ()-Indoline-2-carboxylic Acid Derivatives.

J Org Chem 2021 06 3;86(12):7946-7954. Epub 2021 Jun 3.

Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 13, 56124 Pisa, Italy.

A thorough experimental and computational study on the conformational properties of ()-indoline-2-carboxylic acid derivatives has been conducted. Methyl ()-1-acetylindoline-2-carboxylate, both a mimetic of proline and phenylalanine, shows a remarkable tendency toward the amide isomer when dissolved in polar solvents. This behavior is opposite to the general preference of proline for the isomer, making indoline-2-carboxylic acid a good candidate for the design of different secondary structures and new materials. Read More

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Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 Aug 20;45:128131. Epub 2021 May 20.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. Read More

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Discovery of a novel series of GPR119 agonists: Design, synthesis, and biological evaluation of N-(Piperidin-4-yl)-N-(trifluoromethyl)pyrimidin-4-amine derivatives.

Bioorg Med Chem 2021 Jul 9;41:116208. Epub 2021 May 9.

Cardiovascular & Metabolic Drug Discovery Unit, Takeda Pharmaceutical Company Ltd, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.

We undertook an optimization effort involving propan-2-yl 4-({6-[5-(methanesulfonyl)-2,3-dihydro-1H-indol-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate 1, which we had previously discovered as a novel G protein-coupled receptor 119 (GPR119) agonist. To occupy a presumed hydrophobic space between the pyrimidine and piperidine rings in interaction with GPR119, we replaced the linker oxygen with nitrogen. Subsequently, the introduction of a substituent at the bridging nitrogen atom was explored. Read More

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Palladium-catalyzed asymmetric allylic alkylation of 3-aminooxindoles to access chiral homoallylic aminooxindoles.

Org Biomol Chem 2021 Jun;19(21):4720-4725

Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563000, China. and Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China.

An organometal catalytic conversion of 3-aminooxindoles for the diastereo- and enantioselective synthesis of homoallylic aminooxindoles has been described. The asymmetric allylic alkylation of 3-aminooxindoles with allyl carboxylates proceeded smoothly to afford a series of chiral 3-allyl-3-aminooxindoles. This work offers an alternative route to build these scaffolds. Read More

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Discovery of indoline derivatives as anticancer agents via inhibition of tubulin polymerization.

Bioorg Med Chem Lett 2021 Jul 11;43:128095. Epub 2021 May 11.

School of Basic Medical Sciences, Zhengzhou University Zhengzhou 450001, China. Electronic address:

Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. Read More

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Asymmetric Counteranion Directed Catalytic Heck/Tsuji-Trost Annulation of Aryl Iodides and 1,3-Dienes.

Org Lett 2021 05 7;23(10):3834-3838. Epub 2021 May 7.

Hefei National Laboratory for Physical Sciences at the Microscale and Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.

A chiral anion-mediated asymmetric Heck/Tsuji-Trost reaction of aryl iodides and 1,3-dienes is presented. Chiral indoline derivatives could be afforded with remarkably higher yields and enantioselectivities than our previous chiral ligand-based method. Silver carbonate is employed as both base and halide scavenger to ensure fast and recyclable exchange of the catalytic amount of chiral anions. Read More

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CFSOH-enabled cascade ring-opening/dearomatization of indole derivatives to polycyclic heterocycles.

Org Biomol Chem 2021 May;19(20):4469-4473

College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China.

A novel dearomatization process to produce fused polycyclic indolines via a CF3SO3H-mediated cascade ring-opening of a β-lactam and hydroaminative cyclization is demonstrated. It provides a new strategy for the synthesis of important polycyclic indoline-2-amine derivatives in moderate to excellent yields, as well as with good functional group tolerance. Moreover, transformation of the product was performed to deliver the corresponding acid, alcohol and amide smoothly. Read More

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Chiral Phosphoric Acid-Catalyzed Pictet-Spengler Reactions for Synthesis of 5',11'-Dihydrospiro[indoline-3,6'-indolo[3,2-]qui-nolin]-2-ones Containing Quaternary Stereocenters.

J Org Chem 2021 May 12;86(9):6897-6906. Epub 2021 Apr 12.

State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian 116024, P. R. China.

Chiral phosphoric acid-catalyzed Pictet-Spengler reactions of 2-(1-indolyl)aniline derivatives and isatins by the condensation/cyclization process have been realized. A series of enantioenriched 5',11'-dihydrospiro[indoline-3,6'-indolo[3,2-]quinolin]-2-ones bearing quaternary stereogenic centers were obtained with excellent yields and up to >99% ee. This protocol was suitable for the Pictet-Spengler reactions of 2-(1-benzyl-5-methyl-1-pyrrol-2-yl)aniline, and a variety of 1',5'-dihydro-spiro[indoline-3,4'-pyrrolo[3,2-]quinolin]-2-ones could also be obtained in good yields and up to 88% ee. Read More

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5-Substituted isatin thiosemicarbazones as inhibitors of tyrosinase: Insights of substituent effects.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Jul 9;255:119669. Epub 2021 Mar 9.

College of Chemistry and Environmental Engineering, Institute of Environmental Toxicology and Environmental Ecology, Yancheng Teachers University, Xiwang Avenue South Rd. 2, Yancheng 224007, PR China. Electronic address:

Seven isatin-thiosemicarbazone analogues bearing different substituents (R) attached at C-5 of the indoline ring, TSC-ISA-R (R = -H, -CH, -OCH, -OCF, -F, -Cl and -NO), were synthesized and evaluated as inhibitors of mushroom tyrosinase (TYR). The inhibitory behaviour and performance of TSC-ISA-R were investigated spectroscopically in relation to the substituent modifications through examining their inhibition against the diphenolase activity of TYR using L-DOPA as a substrate. The IC values of TSC-ISA-R were determined to be in the range of 81-209 μM. Read More

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Dispirooxindoles Based on 2-Selenoxo-Imidazolidin-4-Ones: Synthesis, Cytotoxicity and ROS Generation Ability.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory, 1-3, 119991 Moscow, Russia.

A regio- and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoimidazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system-namely, 2-selenoxodispiro[imidazolidine-4,3'-pyrrolidine-2',3″-indoline]-2″,5-diones () and 2-senenoxodispiro[imidazolidine-4,3'-pyrrolidine-4',3″-indoline]-2″,5-diones ()-were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds , , and demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC) 7. Read More

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Molecular interaction study of novel indoline derivatives with EGFR-kinase domain using multiple computational analysis.

J Biomol Struct Dyn 2021 Mar 22:1-10. Epub 2021 Mar 22.

Molecular Signaling Lab, Faculty of Medicine and Health Technology, Tampere University and BioMediTech, Tays Cancer Center, Tampere University Hospital, Tampere, Finland.

Epidermal growth factor receptors are constitutively overexpressed in breast cancer cells, which in turn stimulate many downstream signaling pathways that are involved in many carcinogenic processes. This makes EGFR a striking target for cancer therapy. This study focuses on the EGFR kinase domain inactivation by novel synthesized indoline derivatives. Read More

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A straightforward, environmentally beneficial synthesis of spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-2',10,12-triones mediated by a nano-ordered reusable catalyst.

Sci Rep 2021 Mar 1;11(1):4820. Epub 2021 Mar 1.

Pharmaceutical Research Institute, 8 Rydygiera Street, 01-793, Warsaw, Poland.

A library of new spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-2',10,12-trione derivatives has been prepared in an efficient, one-pot pseudo four-component method mediated by a reusable heterogeneous nano-ordered mesoporous SOH functionalized-silica (MCM-41-SOH) catalyst. Excellent yields, short reaction times, as well as convenient non-chromatographic purification of the products and environmental benefits such as green and metal-free conditions constitute the main advantages of the developed synthetic methodology. The obtained fused indole-indenone dyes would be of interest to pharmaceutical and medicinal chemistry. Read More

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A palladium-catalyzed cascade process for spirooxindole: an alternative way for the synthesis of spiro(indoline-3,2'-quinazolin)-2-ones.

Org Biomol Chem 2021 03;19(8):1795-1806

Applied Organic Chemistry Group, Chemical Science and Technology Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam, India. and Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

A palladium-catalyzed cascade strategy has been developed for one-pot synthesis of functionalized spiro(indoline-3,2'-quinazolin)-2-one derivatives from readily available starting materials. The reaction proceeds via C-C and two C-N bond formations in a single reaction operation. This method offers an attractive pathway for the synthesis of a broad range of spiro(indoline-3,2'-quinazolin)-2-ones in good yields. Read More

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Discovery of a novel series of indolinylpyrimidine-based GPR119 agonists: Elimination of ether-a-go-go-related gene liability using a hydrogen bond acceptor-focused approach.

Bioorg Med Chem 2021 Mar 23;34:116034. Epub 2021 Jan 23.

Cardiovascular & Metabolic Drug Discovery Unit, Takeda Pharmaceutical Company Ltd, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.

We previously identified a novel series of indolinylpyrimidine derivatives exemplified by 2 in Figure 1, which is an indoline based derivative, as potent GPR119 agonists. Despite the attractive potency of 2, this compound inhibited the human ether-a-go-go-related gene (hERG) K channel. We elucidated crucial roles of the methylsulfonyl group of 2 in its interaction with the hERG channel and the GPR119 receptor, presumably as a hydrogen bond acceptor (HBA). Read More

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A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication.

Nat Commun 2021 01 28;12(1):668. Epub 2021 Jan 28.

Department of Refractory Viral Infections, National Center for Global Health and Medicine Research Institute, Tokyo, Japan.

Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (M). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC values of 15 ± 4 and 4. Read More

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January 2021

Visible-Light-Induced Intramolecular Double Dearomative Cycloaddition of Arenes.

Angew Chem Int Ed Engl 2021 Mar 24;60(13):7036-7040. Epub 2021 Feb 24.

State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai, 200032, China.

Herein we report visible-light-induced intramolecular double dearomative cycloaddition of arenes. Compared with the well-known photodimerization of arenes under ultraviolet irradiation, the current reactions are carried out under mild conditions and feature wide substrate scope. A large array of structurally-diverse polycyclic indoline derivatives is afforded in high yields (up to 98 %) with exclusive diastereoselectivity (>20:1 dr) via dearomative [4+2] or [2+2] pathway. Read More

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Palladium-Catalyzed Enantioselective Heteroarenyne Cycloisomerization Reaction.

Angew Chem Int Ed Engl 2021 03 24;60(13):7412-7417. Epub 2021 Feb 24.

College of Chemical Engineering, State Key Laboratory Breeding Base of Green-Chemical Synthesis Technology, Zhejiang University of Technology, Chaowang Road #18, Hangzhou, 310014, China.

The extensively developed ene-type enantioselective cycloisomerization of classical 1,n-enynes provides an efficient approach to chiral cyclic 1,4-dienes. In contrast, the catalytic asymmetric heteroarenyne (heteroarene-alkyne) cycloisomerization involving the dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH-catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne-tethered indole substrates (formal 1,5- and 1,6-enynes). Read More

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Analysis of a "3-(Naphthalen-1-ylimino) Indoline-2-one" compound and Its Antimicrobial Assessment Using Lipid-based Self-nanoemulsifying Formulations.

Molecules 2020 Dec 22;26(1). Epub 2020 Dec 22.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

In recent years, indole derivatives have acquired conspicuous significance due to their wide spectrum of biological activities-antibacterial, antiviral, and anticonvulsant. This compound is derived from naturally grown plants. Therefore, synthesis of a novel "3-(Naphthalen-1-ylimino) indoline-2-one" compound () and its analysis using UPLC systems along with antimicrobial assessment was the aim of the current study. Read More

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December 2020

Grindstone Chemistry: Design, One-Pot Synthesis, and Promising Anticancer Activity of Spiro[acridine-9,2'-indoline]-1,3,8-trione Derivatives against the MCF-7 Cancer Cell Line.

Molecules 2020 Dec 11;25(24). Epub 2020 Dec 11.

Department of Chemistry, Nehru Memorial College, Affiliated Bharathidasan University, Puthanamapatti, Tamilnadu 621007, India.

In this study, the synthesis of one-pot 10-phenyl-3,4,6,7-tetrahydro-1-spiro [acridine-9,2'-indoline]-1,3,8-trione derivatives was achieved via a four-component cyclocondensation reaction, which was carried out in solvent-free conditions, and using p-toluenesulfonic acid (p-TSA) as a catalyst. The product was confirmed by FT-IR, H-NMR, C-NMR, mass spectra, and elemental analysis. Furthermore, the anticancer activity was screened for all compounds. Read More

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December 2020

Design, synthesis, evaluation, and SAR of 4-phenylindoline derivatives, a novel class of small-molecule inhibitors of the programmed cell death-1/ programmed cell death-ligand 1 (PD-1/PD-L1) interaction.

Eur J Med Chem 2021 Feb 10;211:113001. Epub 2020 Nov 10.

Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China. Electronic address:

The blockade of the PD-1/PD-L1 immune checkpoint pathway with small molecules is an emerging immunotherapeutic approach. A novel series of 4-phenylindoline derivatives were synthesized, and their inhibitory activity against the PD-1/PD-L1 protein-protein interaction (PPI) was evaluated through a homogenous time-resolved fluorescence (HTRF) assay. Among them, A20 and A22 exhibited potent activity with IC values of 17 nM and 12 nM, respectively. Read More

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February 2021

Convergent Synthesis of Triindanone-Fused Spiro[bicyclo[2.2.2]octane-2,3'-indolines] via Domino Reaction of 1,3-Indanedione and 3-Methyleneoxindoles.

Org Lett 2020 Nov 9;22(22):8931-8936. Epub 2020 Nov 9.

College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou 225002, China.

A triethylamine-promoted domino reaction of three molecular 1,3-indanediones with various 3-methyleneoxindoles in refluxing ethanol has been developed. Series of novel polycyclic triindanone-fused spiro[bicyclo[2.2. Read More

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November 2020

Blue Light-Promoted Formal [4+1]-Annulation of Diazoacetates with -Aminoacetophenones: Synthesis of Polysubstituted Indolines and Computational Study.

J Org Chem 2020 11 9;85(21):13920-13928. Epub 2020 Oct 9.

Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.

A blue light-promoted formal [4+1]-annulation of diazoacetates with -aminoacetophenones has been reported, which provides an environmentally friendly method for the synthesis of polysubstituted indoline derivatives in moderate to good yields with excellent diastereoselectivities. Detailed mechanistic studies through density functional theory calculations reveal that the ()-enol species is the key intermediate in this transformation, and the excellent diastereoselectivity is enabled -bonding in the intramolecular Aldol-type addition. Read More

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November 2020

Preparation and analysis of photochromic behavior of carboxymethyl chitin derivatives containing spiropyran moieties.

Des Monomers Polym 2020 Jul 26;23(1):106-117. Epub 2020 Jul 26.

College of Materials Science and Engineering, Xi'an University of Technology, Xi'an, China.

1'-(2-Acryloxyethyl)-3,3'-dimethyl-6-nitrospiro[2 -1-benzopyran-2,2'-indoline] (SPA) was synthesized and grafted onto a water-soluble carboxymethyl chitin (CMCH) macromolecule to prepare a photochromic copolymer (CMCH-g-SPA). The structure of CMCH-g-SPA was characterized by Fourier-transform infrared (FT-IR) spectroscopy, thermogravimetric (TG) analysis, X-ray diffraction (XRD) analysis, water-solubility evaluation, and UV-vis spectroscopy. XRD patterns of CMCH-g-SPA revealed that grafting copolymerization disrupts the CMCH semicrystalline structure, thus improving water solubility. Read More

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Unprecedented Regio- and Stereoselective Synthesis of Pyrene-Grafted Dispiro[indoline-3,2'-pyrrolidine-3',3″-indolines]: Expedient Experimental and Theoretical Insights into Polar [3 + 2] Cycloaddition.

ACS Omega 2020 Sep 14;5(37):24081-24094. Epub 2020 Sep 14.

Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, 21955 Makkah, Saudi Arabia.

A series of dispiro[indoline-3,2'-pyrrolidine-3',3″-indolines] was synthesized via a multicomponent polar [3 + 2] cycloaddition (32CA) reaction of isatin derivatives, sarcosine and ()-3-(2-oxo-2-(pyren-1-yl)ethylidene)indolin-2-one derivatives. The regio- and stereochemistries of the cycloadducts were established on the basis of one-dimensional (1D) (H-, C-, C-CRAPT NMR) and two-dimensional (2D) homonuclear and heteronuclear correlation NMR spectrometry experiments (H-H gDQFCOSY, C-H-HSQCAD, C-H-HMBCAD, H-H-ROESYAD). The molecular mechanism and regio- and stereoselectivities of the cycloaddition (CA) reaction have been investigated utilizing a density functional theory (DFT) method and were thoroughly explained based on the transition-state stabilities and global/local electrophilicity/nucleophilicity reactivity indices of the reactants. Read More

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September 2020

Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1-pyridazino[3,4-]indoles.

Molecules 2020 Sep 9;25(18). Epub 2020 Sep 9.

Department of Biomolecular Sciences, Section of Chemistry and Pharmaceutical Technologies, University of Urbino "Carlo Bo", Via I Maggetti 24, 61029 Urbino, Italy.

Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1-pyridazino[3,4-]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). Read More

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September 2020

Bioinspired Divergent Oxidative Cyclization from Strictosidine and Vincoside Derivatives: Second-Generation Total Synthesis of (-)-Cymoside and Access to an Original Hexacyclic-Fused Furo[3,2-b]indoline.

Chemistry 2020 Dec 18;26(71):17190-17194. Epub 2020 Nov 18.

Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Université Paris-Saclay, CNRS, 91405, Orsay, France.

The second-generation synthesis of (-)-cymoside as well as the formation of a new hexacyclic-fused furo[3,2-b]indoline framework is reported. After a Pictet-Spengler condensation between secologanin tetraacetate and tryptamine, the course of the cyclization of the 7-hydroxyindolenine intermediate, generated by oxidation with an oxaziridine, depended on the stereochemistry of the 3-position. The 3-(S)-strictosidine stereochemistry delivered efficiently the scaffold of cymoside via intramolecular coupling with the C16-C17 enol ether, while the 3-(R)-vincoside stereochemistry directed towards the reaction with the C18-C19 terminal alkene and the formation of the unexpected caged compound. Read More

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December 2020

Direct C3-Selective Arylation of N-Unsubstituted Indoles with Aryl Chlorides, Triflates, and Nonaflates Using a Palladium-Dihydroxyterphenylphosphine Catalyst.

J Org Chem 2020 08 11;85(16):10902-10912. Epub 2020 Aug 11.

School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.

A palladium-dihydroxyterphenylphosphine (DHTP) catalyst was successfully applied to the direct C3-arylation of N-unsubstituted indoles with aryl chlorides, triflates, and nonaflates. This catalyst showed C3-selectivity, whereas catalysts with other structurally related ligands exhibited N1-selectivity. Complex formation between the lithium salts of the ligand and the indole is assumed to accelerate the arylation at the C3 position. Read More

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