Regioexhaustive Functionalization of the Carbocyclic Core of Isoquinoline: Concise Synthesis of Oxoaporphine Core and Ellipticine

Horváth, Dániel; Domonyi, Frigyes; Palkó, Roberta; Lomoschitz, Andrea; Soós, Tibor

doi:10.1055/s-0037-1609153

Cited by 7 publications

(2 citation statements)

References 4 publications

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“…Generally, synthetic strategies leading to the target molecule are classified according to assembly of the last ring as B, C, D, and B + C types (Passemar et al, 2011) [10] (see Figure 1). Among the different synthetic routes available [21][22][23][24][25][26][27][28][29], the method originally proposed by Cranwell and Saxton appears to be the most practical one [21,30]. It consists of a five-stage ''D-type'' procedure starting from appropriately substituted indoles or carbazoles.…”

Section: Introductionmentioning

confidence: 99%

Indole alkaloid ellipticine as efficient multitarget compound

et al. 2022

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First isolated from the tropical plant Oschrosia elliptica, indole alkaloid ellipticine provoked huge interest since it demonstrated antitumor activity was demonstrated along with limited toxic side effects and a complete lack of hematological toxicity. In this work, a five-step Cranwell and Saxton synthesis was used for obtaining ellipticine (Ell). Ellipticine hydrochloride salt (Ell×HCl) was also synthesized. Detailed in vitro studies of anticancer, antimalarial, and leishmanicidal activities were performed. Antiproliferation assay using DU145 cancer cell line treated with Ell showed a consistent reduction in cell proliferation and cell viability when treated with 5 μmol Ell. Anti-proliferation activity was more pronounced for the Ell×HCl solutions. Both the Ell and Ell×HCl revealed moderate activity in vitro against Leishmania amazonensis promastigotes, which is related to insufficient solubility of the drugs. IC50 values of Ell and Ell×HCl were determined in vitro against multidrug resistant Plasmodium falciparum strain K1. The Ell×HCl was shown to be almost three times more potent than the Ell in DMSO. Upon dilution with water, Ell solubility and activity drops down, while the activity and solubility of Ell×HCl is enhanced up to 10 times in 50:50 aqueous DMSO solutions

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Section: Introductionmentioning

confidence: 99%

Indole alkaloid ellipticine as efficient multitarget compound

et al. 2022

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“…Ellipticine derivatives such as 9-hydroxy-2-methylellipticinium acetate (NHME) had been introduced into the market, but were later withdrawn. [6] The search for other ellipticine derivatives is under way [10][11][12][13][14][15][16]. However, low water solubility of ellipticine derivatives is a crucial obstacle for the wide practical application in cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

et al. 2020

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Cancer still remains a major public health concern around the world and the search for new potential antitumor molecules is essential for fighting the disease. This study evaluated the anticancer and immunomodulatory potential of the newly synthetized ellipticine derivate: sodium bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate (Br-Ell-SO3Na). It was prepared by the chlorosulfonation of 9-bromoellipticine. The ellipticine-7-sulfonic acid itself is not soluble, but its saponification with sodium hydroxide afforded a water-soluble sodium salt. The cytotoxicity of Br-Ell-SO3Na was tested against cancerous (K562 cell line) and non-cancerous cells (Vero cell line and human peripheral blood mononuclear cells (PBMC)) using a Methylthiazoletetrazolium (MTT) assay. Cell cycle arrest was assessed by flow cytometry and the immunomodulatory activity was analyzed through an enzyme-linked immunosorbent assay (ELISA). The results showed that the Br-Ell-SO3Na molecule has specific anticancer activity (IC50 = 35 µM) against the K562 cell line, once no cytotoxicity effect was verified against non-cancerous cells. Cell cycle analysis demonstrated that K562 cells treated with Br-Ell-SO3Na were arrested in the phase S. Moreover, the production of IL-6 increased and the expression of IL-8 was inhibited in the human PBMC treated with Br-Ell-SO3Na. The results demonstrated that Br-Ell-SO3Na is a promising anticancer molecule attested by its noteworthy activity against the K562 tumor cell line and immunomodulatory activity in human PBMC cells.

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Total Synthesis of Suberitines A–D Featuring Tunable Biomimetic Late‐Stage Oxidative Dearomatization and Acetalization

Tang

Gao

et al. 2022

Chemistry A European J

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Aaptaminoids are a unique family of marine alkaloids bearing a benzo[de][1,6]‐naphthyridine core. This work describes the first total synthesis of suberitines A–D (1–4), four typical dimeric natural aaptaminoids, employing a step‐saving bidirectional strategy. Key methods applied in the total synthesis include a cationic cascade to construct the bis‐isoquinoline(s) with Hendrickson reagent‐mediated Friedel‐Crafts‐type cyclization and eliminative aromatization, and a Bronsted acid‐promoted Vilsmeier cyclization to generate the naphthyridine(s). The conditionally tunable PIDA‐mediated oxidative dearomatization and subsequent methanolysis or hydrolysis successfully served as a powerful biomimetic tool to elaborate the essential oxygenated functionalities of suberitines A–D (1–4) in proper solvent‐combinations at the final stage of total synthesis. The biomimetic proposal employed in the late‐stage redox interchanges of related natural products was eventually supported by the isolation of synthetic intermediate 23 a as a natural product from the same natural source. Biological screening revealed that five of the synthetic samples including two natural suberitines and three full‐skeleton natural product‐like intermediates exhibited low micromolar inhibitory activities against the growth of cancer cell line K562.

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Regioexhaustive Functionalization of the Carbocyclic Core of Isoquinoline: Concise Synthesis of Oxoaporphine Core and Ellipticine

Cited by 7 publications

References 4 publications

Indole alkaloid ellipticine as efficient multitarget compound

Indole alkaloid ellipticine as efficient multitarget compound

Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

Total Synthesis of Suberitines A–D Featuring Tunable Biomimetic Late‐Stage Oxidative Dearomatization and Acetalization

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