An Improved Synthesis of Protoanemonin<sup>1</sup>

Grundmann, Christoph; Kober, Ehrenfried

doi:10.1021/ja01613a092

Cited by 69 publications

(32 citation statements)

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“…(27). All other reagents and solvents were of the highest available grade from Sigma-Aldrich Chemical Co. or Fisher Scientific Co. and were used as received.…”

Section: Methodsmentioning

confidence: 99%

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

et al. 2005

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Release of 5-methylene-2-furanone (5-MF), a characteristic marker of DNA deoxyribose oxidative damage at the C1′ position, was observed in significant quantities from X-irradiated DNA. This observation, which held for DNA irradiated either in aqueous solution or as a film, requires postirradiation treatment at 90° C in the presence of polyamines and divalent metal cations at biological pH. The 5-MF product was quantified by using reverse-phase HPLC. The radiation chemical yield of 5-MF comprised more than 30% of the yield of total unaltered base release. Polylysine, spermine and Be(II) showed the strongest catalytic effect on 5-MF release, while Zn(II), Cu(II), Ni(II), putrescine and Mg(II) were substantially less efficient. We have hypothesized that the 5-MF release from irradiated DNA occurs through catalytic decomposition of the 2′ -deoxyribonolactone (dL) precursor through two consecutive β -and δ -phosphate elimination reactions. A stepwise character of the process was indicated by the S-shaped time course of 5-MF accumulation. If dL proves to be the precursor to 5-MF formation, it would then follow that dL is a very important lesion generated in DNA by ionizing radiation.

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“…(27). All other reagents and solvents were of the highest available grade from Sigma-Aldrich Chemical Co. or Fisher Scientific Co. and were used as received.…”

Section: Methodsmentioning

confidence: 99%

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

et al. 2005

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“…The product 3 used as a reference compound in HPLC experiments was synthesized according to a published procedure. [13] All the DNA oligonucleotides used in this study were purified by semipreparative RP HPLC. The "dry" films containing the oligonucleotides (≈500 μg) were prepared from aqueous solution (200 μL) dried over saturated NaOH (5% relative humidity) on a microscope glass slide and then subjected to vacuum overnight.…”

Section: Methodsmentioning

confidence: 99%

2‐Deoxyribonolactone Lesions in X‐ray‐Irradiated DNA: Quantitative Determination by Catalytic 5‐Methylene‐2‐furanone Release

2005

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KeywordsDNA cleavage; DNA; oligonucleotides; X-rays The C1′-oxidized abasic DNA lesion 2-deoxyribonolactone (dL, 1) has attracted significant attention in recent years owing to its potential mutagenicity, which is associated with the ability of lesion 1 to misincorporate nucleotides during DNA synthesis, its resistance to base-excisionrepair (BER) enzymes, and its ability to form cross-links with BER enzymes efficiently. [1] Lesion 1 is produced in model systems by the action of a number of DNA-damaging agents such as copper(I)phenanthroline, [2] other metal complexes, [3] enediyne antibiotics, [4] as well as by UV light, [5] photosensitization, [6] and ionizing radiation. [7] However, the formation of 1 in vivo and its biological effects have been poorly documented. Until recently, lesion 1 in model systems has been identified primarily by detection of its low-molecular decomposition product 5-methylene-2-furanone (5-MF, 3). [2b,8] Only recently has a method for the selective detection of 1 been developed based on its reactivity with biotinylated cysteine. [9] Lesion 1 is relatively unstable; decomposition of 1, which is significantly accelerated by heating or alkaline treatment, results in strand scission and release of 3 (Scheme 1). [10][11][12] Decomposition of 1 is a two-step process: β elimination of the 3′-phosphate fragment forms butenolide 2, and δ elimination of the 5′-phosphate fragment produces 3 as the final product. The product 3 is unstable at basic pH values and hence cannot be detected upon alkaline decomposition of 1.In our recent paper [8] we demonstrated that 3, a characteristic decomposition product of 1, is released from X-irradiated calf thymus DNA upon postirradiation treatment with DNAphosphate-binding catalysts such as spermine. We hypothesized that 1 is a precursor to 3 in irradiated DNA and suggested that the yield of 1 in DNA can be quantified by using the yield of released 3.Herein we report the isolation of dL-containing tetramers from X-irradiated d(CGCG) and d (pCGCG) films, with the dL lesions corresponding to all four positions of the d-(C 1 G 2 C 3 G 4 ) tetramer. We demonstrate that these dL-containing tetramers undergo catalytic decomposition with quantitative release of 3. These results provide proof that lesion 1 is the major, perhaps only, precursor to 3 in irradiated highly polymerized DNA.

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“…The members of this class of compounds vary greatly in structural complexity, as well as functionality. Besides that, many of them have been shown to display a wide range of biological activities, such as the antibiotic activity displayed by protoanemonin [5][6][7], the cytotoxicity associated with the goniobutenolides A and B [8][9][10][11][12], and the inhibition of cholesterol biosynthesis observed with xerulin and xerulinic acid [13][14]. Two other interesting examples of γ-alkylidenebutenolides are the compounds 3-methyl-2H-furo [2,3-c]pyran-2-one and peridinin.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxic Activity of Some 3-Benzyl-5-Arylidenefuran-2(5H)-ones

et al. 2007

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3-Benzyl-furan-2(5H)-one (2a) and 3-(4-bromobenzyl)-furan-2(5H)-one (2b) were treated with TBDMSOTf and converted into the corresponding tert-butyldimethylsilylfuran ethers. These furans were further condensed with several aromatic aldehydes affording compounds 5-14 with general 3-benzyl-5-arylidene-furan-2(5H)-one structures in 31% to 98% yields. Such compounds are analogues of the naturally occurring nostoclide lactones, reported to present moderate cytotoxic activity. Compounds 5-14 were submitted to an in vitro bioassay against the HL-60, HCT-8, SF295 and MDA-MB-435 cancer cell lines using the MTT cytotoxicity assay.

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An Improved Synthesis of Protoanemonin¹

Cited by 69 publications

References 0 publications

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

2‐Deoxyribonolactone Lesions in X‐ray‐Irradiated DNA: Quantitative Determination by Catalytic 5‐Methylene‐2‐furanone Release

Synthesis and Cytotoxic Activity of Some 3-Benzyl-5-Arylidenefuran-2(5H)-ones

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An Improved Synthesis of Protoanemonin1

Cited by 69 publications

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The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

The Release of 5-Methylene-2-Furanone from Irradiated DNA Catalyzed by Cationic Polyamines and Divalent Metal Cations

2‐Deoxyribonolactone Lesions in X‐ray‐Irradiated DNA: Quantitative Determination by Catalytic 5‐Methylene‐2‐furanone Release

Synthesis and Cytotoxic Activity of Some 3-Benzyl-5-Arylidenefuran-2(5H)-ones

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An Improved Synthesis of Protoanemonin¹