Salarins A and B and Tulearin A:  New Cytotoxic Sponge-Derived Macrolides

Bishara, Ashgan; Rudi, Amira; Aknin, Maurice; Neumann, Drorit; Ben‐Califa, Nathalie; Kashman, Yoel

doi:10.1021/ol702221v

Cited by 45 publications

(45 citation statements)

References 12 publications

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“…After purification, the spectra of the synthetic samples compared very favorably to those of the authentic natural product. [6,7] Total Synthesis of Tulearin A Tulearin A (1) differs from its sister compound tulearin C (2) only by a single carbamate. For the lack of any electronic or steric bias however, it seemed unreasonable to assume that this group could be attached selec- tively to the C8-OH group of 2 or any of its immediate synthetic precursors.…”

Section: Formation Of Non-terminal Alkynes By Reductive Alkylationmentioning

confidence: 99%

“…The spectral data of synthetic tulearin A (1) thus formed compare favorably with those of the natural product isolated from the Madagascan Fascaplysinopsis sponge (see the Supporting Information). [6,7] …”

Section: Formation Of Non-terminal Alkynes By Reductive Alkylationmentioning

confidence: 99%

“…[6,7] Although the limited supply from the natural source made a detailed biological evaluation impossible, preliminary data for tulearin A (1) indicated a differential cytotoxicity against two human leukemia cell lines. [6] This may well be the reason for the immediate interest that these targets arose in the preparative community, [8,9] although their stereostructure had originally not been established [6] and could be assigned only after a crystalline derivative of 1 had be obtained. [7] Therefore, a prompt foray by Cossy and co-workers targeted what ultimately turned out to be an unnatural isomer; [8] their synthesis was based on a macrocyclization at the C12ÀC13 bond by ring-closing olefin metathesis (RCM).…”

Section: Introductionmentioning

confidence: 99%

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A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

Lehr

Schulthoff

Ueda

et al. 2014

Chemistry A European J

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Lactones are known to react with the reagent generated in situ from CCl4 and PPh3 in a Wittig-type fashion to give gem-dichloro-olefin derivatives. Such compounds are now shown to undergo reductive alkylation on treatment with organolithium reagents RLi to furnish acetylene derivatives bearing the substituent R at their termini (R=Me, n-, sec-, tert-alkyl, silyl); the reaction can be catalyzed with either Cu(acac)2 or Fe(acac)3 /1,2-diaminobenzene. Two alkynol derivatives prepared in this way from readily accessible lactone precursors served as the key building blocks for the total syntheses of the cytotoxic marine macrolides tulearin A (1) and C (2). The assembly of these fragile targets hinged upon ring closing alkyne metathesis (RCAM) followed by a formal trans-reduction of the resulting cycloalkynes via trans-hydrosilylation/protodesilylation.

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Section: Formation Of Non-terminal Alkynes By Reductive Alkylationmentioning

confidence: 99%

Section: Formation Of Non-terminal Alkynes By Reductive Alkylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

Lehr

Schulthoff

Ueda

et al. 2014

Chemistry A European J

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“…1). Each compound was characterized by MS, and 1D and 2D NMR spectra [5,6,8]. We used several batches of salarin C isolates, all of which displayed similar activities at the applied concentrations.…”

Section: Salarin Congenersmentioning

confidence: 99%

“…sponge collected in Salary Bay, ∼100 km north of Tulear. Bio-guided (brine shrimp test) separation of CHCl 3 -CH 3 OH (1:1) extract provided four groups of novel compounds-salarins, tulearins, taumycins and tausalarins-containing unique functionalized nitrogenous macrocycles [4][5][6][7]. In the present study, we examined the ability of a panel of natural salarins to inhibit proliferation and induce cell death in the K562 human leukemia cell line.…”

Section: Introductionmentioning

confidence: 99%

Salarin C, a member of the salarin superfamily of marine compounds, is a potent inducer of apoptosis

et al. 2010

Self Cite

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The continuous emergence of new diseases and the development of drug-resistant cancers necessitate the development of new drugs with novel mechanisms of action. The richest marine source of natural anti-cancer products has been soft-bodied organisms that lack physical defenses against their predators, and hence rely on chemical defense mechanisms using cytotoxic secondary metabolites. Bio-guided (brine shrimp test) separation of CHCl(3)-CH(3)OH (1:1) extract from the Madagascar Fascaplysinopsis sp. sponge provided several new compounds. Here we focused on the biological activity of a panel of novel natural compounds, salarins A-J. Of these, salarin C was the most potent inhibitor of proliferation, as demonstrated on the K562 leukemia cell line. Salarin C-treated K562 cells underwent apoptotic death as monitored by cell-cycle analysis, annexin V/propidium iodide staining, cleavage of poly-ADP-ribose polymerase (PARP) and caspase 3, and caspase 9 levels. The experimental approach described herein is an essential step towards identifying the cellular pathway(s) affected by salarin C and producing potent synthetic derivatives of salarin C with potential future uses as basic research tools and/or drugs and drug leads.

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An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

Vaske

Crews

2013

Bioactive Compounds From Marine Foods

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In this chapter we discuss a selection of structurally diverse marine-derived small molecules (MDSMs) with potent and/or specific bioactivity and analyze their biomedical applications. The compounds included have been isolated either from marine macroorganisms, including sponges, ascidians (tunicates), bryozoans, and molluscs, or from microorganisms, such as bacteria and fungi. Our inquiry begins with a look back in time at a selection of important marine natural products, with particular focus on compounds in the clinical pipeline. The chapter continues with an analysis of a biosynthetically diverse assortment of 22 MDSMs and their structural elements of atom and stereochemical diversity. Entries have been divided into five biosynthetic classes: terpene, polyketide, alkaloid, depsipeptide, and polyketide-peptide. Enormous structural variety is represented by the marine natural products treated herein. The compounds selected can be considered to represent case examples of significant biomolecules with positivity and, in some cases, potent bioactivity accompanied by an unusual mechanism of action. Overview of known compounds, highlighting molecules of significanceThe ocean covers more than 70% of the earth's surface and is home to exceptional biodiversity: more than one million marine species and an estimated one billion different kinds of marine microbe (Census of Marine Life Press Release 2010). We and others firmly believe that MDSMs represent a continuing resource for tools important in cell biology research and in the design of the next-generation leads for drug discovery and development. The record to date firmly illustrates that the structures of natural products continue to be invaluable in expanding pharmacophore structural space. For example, Newman and Cragg recently provided a detailed analysis of the last 30 years of natural products in drug discovery, wherein they contended that, "Nature's 'treasure trove of small molecules' remains to be explored, particularly from the marine and microbial environments" (Newman & Cragg 2012).

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Salarins A and B and Tulearin A: New Cytotoxic Sponge-Derived Macrolides

Cited by 45 publications

References 12 publications

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

A New Method for the Preparation of Non‐Terminal Alkynes: Application to the Total Syntheses of Tulearin A and C

Salarin C, a member of the salarin superfamily of marine compounds, is a potent inducer of apoptosis

An Update on the Biomedical Prospects of Marine‐derived Small Molecules with Fascinating Atom and Stereochemical Diversity

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