A New, Titanium-Mediated Approach to Pyrroles: First Synthesis of Lukianol A and Lamellarin O Dimethyl Ether

Fürstner, Alois; Weintritt, Holger; Hupperts, Achim

doi:10.1021/jo00125a068

Cited by 206 publications

(96 citation statements)

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“…The synthetic pathways started with the Sheffer-Weitz-epoxidation of an enone I, as depicted in Scheme 7a, followed by a Lewis acid-mediated rearrangement and condensation with hydroxylamine to afford the corresponding isoxazole II. Cleavage of the N-O bond, condensation, and McMurry cyclization were the subsequent steps to yield lamellarin O dimethyl ester (Scheme 7a) [104]. Another alternative for type-II lamellarin synthesis was performed by cross-coupling using the Stille, Suzuki or Negishi methods, as described by Banwell et al in 1997.…”

Section: Lamellarins and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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Section: Lamellarins and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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“…The substituted pyrroles, which were synthesized based on similarity to marine derived compounds [1,2], have previously been demonstrated to have significant growth inhibitory activity against a variety of human tumor cell lines, with antiproliferative effects evident at nanomolar concentrations in some human breast tumor cell lines [3][4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison

Arthur

Gupton

Kellogg

et al. 2007

Biochemical Pharmacology

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JG-03-14, a substituted pyrrole that inhibits microtubule polymerization, was screened against MCF-7 (p53 wild type), MDA-MB 231 (p53 mutant), MCF-7/caspase 3 and MCF-7/ADR (multidrug resistant) breast tumor cell lines. Cell viability and growth inhibition were assessed by the crystal violet dye assay. Apoptosis was evaluated by the TUNEL assay, cell cycle distribution by flow cytometry, autophagy by acridine orange staining of vesicle formation, and senescence based on β-galactosidase staining and cell morphology. Our studies indicate that exposure to JG-03-14, at a concentration of 500 nM, induces time dependent cell death in the MCF-7 and MDA-MB 231 cell lines. In MCF-7 cells, a residual surviving cell population was found to be senescent; in contrast, there was no surviving senescent population in treated MDA-MB 231 cells. No proliferative recovery was detected over a period of 15 days post-treatment in either cell line. Both the TUNEL assay and FLOW cytometry indicated a relatively limited degree of apoptosis (< 10%) in response to drug treatment in MCF-7 cells with more extensive apoptosis (but < 20%) in MDA-MB231 cells; acidic vacuole formation indicative of autophagic cell death was relatively extensive in both MCF-7 and MDA-MB231 cells. In addition, JG-03-14 induced the formation of a large hyperdiploid cell population in MDA-MB231 cells. JG-03-14 also demonstrated pronounced anti-proliferative activity in MCF-7/caspase 3 cells and in the MCF-7/ADR cell line. The observation that JG-03-14 promotes autophagic cell death and also retains activity in tumor cells expressing the multidrug resistance pump indicates that novel microtubule poisons of the substituted pyrroles class may hold promise in the treatment of breast cancer.

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“…2а Although arylpyrroles are applied for the synthesis of fluorescent azaindacene dyes of BODIPY family 4 as well as optoelectronic materials, 5 it is their pharmacological appeal that seems to be the chief reason for a steady interest in the development of synthetic procedures for these compounds, reported, in particular, in reviews. 1,2 Di-and triphenylpyrroles are normally prepared by condensation of 1,4-diketones with ammonia or ammonium acetate, [6][7][8][9] as well as by the reaction of 1,3-diketones 10,11 with different nitrogen-containing compounds (ammonium acetate, aromatic imines, oximes) followed by cyclization of the intermediates formed. Despite the satisfactory yields of the target products, the syntheses reported feature either hard availability of the starting materials 12 or multi-step procedures.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the satisfactory yields of the target products, the syntheses reported feature either hard availability of the starting materials 12 or multi-step procedures. 10 The reaction of ketoximes with acetylene (the Trofimov reaction) in the superbase systems МОН-DMSO, where М = Li, Na, K, makes it possible to prepare a wide series of substituted pyrroles in one preparative step. 1,13 While this reaction is mostly studied with unsubstituted acetylene the applicability of phenylacetylene, an available substituted acetylene, still remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Reaction of acetophenone and benzylphenylketone oximes with phenylacetylene: synthesis of di- and triphenylpyrroles

Петрова¹,

Sobenina²,

Ushakov³

et al. 2008

Arkivoc

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The reaction of oximes of aromatic ketones with phenylacetylene in the presence of superbase systems (MOH-DMSO, where M = Li, Na, K) has been extensively studied for the first time. The effects of alkaline metal cation, the ketoximes structure and the reaction conditions (temperature, duration) on the products composition have been evaluated. Acetophenone oxime reacts with phenylacetylene (МОН-DMSO, where M = Li, Na, K, 140 о С, 6 h) to afford 2,5-diphenyl-1H-pyrrole in 14-18% isolated yield. The reaction of benzylphenylketoxime with phenylacetylene (LiОН-DМSО, 120 о С, 12 h) delivers 2,3,4-, 2,3,5-triphenyl-1H-pyrroles (in 17% total yield) and 2,3,4-triphenyl-1-[(Z)-2-phenylethenyl]-1H-pyrrole (7% yield).

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A New, Titanium-Mediated Approach to Pyrroles: First Synthesis of Lukianol A and Lamellarin O Dimethyl Ether

Cited by 206 publications

References 0 publications

Marine Natural Products as Models to Circumvent Multidrug Resistance

Marine Natural Products as Models to Circumvent Multidrug Resistance

Autophagic cell death, polyploidy and senescence induced in breast tumor cells by the substituted pyrrole JG-03-14, a novel microtubule poison

Reaction of acetophenone and benzylphenylketone oximes with phenylacetylene: synthesis of di- and triphenylpyrroles

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