Determination by Asymmetric Total Synthesis of the Absolute Configuration of Lucilactaene, a Cell‐Cycle Inhibitor in p53‐Transfected Cancer Cells

Yamaguchi, Junichiro; Kakeya, Hideaki; Uno, Takao; Shoji, Mitsuru; Osada, Hiroyuki; Hayashi, Yujiro

doi:10.1002/ange.200500060

Cited by 12 publications

(13 citation statements)

References 28 publications

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“…[13] In 1-5, the decalin rings were derived from an octaketide intermediate and five S-adenosylmethionines (see the Supporting Information). The deoxy-tetramic acid moieties of 1 and 2 were proposed following the fusarin C [14] and lucilactaene [15] modes. The octaketide intermediate reacts with homoleucine aldehyde to form 1,5-dihydronpyrrol-2-one, which may undergo tautomerization, epoxidation, and isomerization to produce the racemic 5-alkyl-5-hydroxyl-1H-pyrrol-2(5H)-ones.…”

Section: Resultsmentioning

confidence: 99%

“…For instance, some natural products, such as lipstatin, lactacystin, and some l-trans-(S,S)-epoxysuccinic acids actively react with target enzymes to form covalent complexes. [16] Some reports of deoxy-tetramic acids [12,15] suggest that an intramolecular OH group or extraction and isolation solvent molecules can attack the b position of an a,b-unsaturated ketone by way of a Michael reaction during the biogenetic route or in the processes of isolation and purification to form artificial products. The mechanism of action of 1-5 is currently under investigation.…”

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confidence: 99%

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Cytotoxic Polyketides Containing Tetramic Acid Moieties Isolated from the Fungus Myceliophthora Thermophila: Elucidation of the Relationship between Cytotoxicity and Stereoconfiguration

Yang

Chen

et al. 2007

Chemistry A European J

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Five new polyketides that contain tetramic acids, myceliothermophins A-E, were isolated from the thermophilic fungus Myceliophthora thermophila. Two sets of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one diastereomers, myceliothermophins A/B and C/D, were separated as pure compounds by using silica-gel column chromatography and recycling reverse-phase high-performance liquid chromatography (RP-HPLC). The relative configurations of the chiral centers in 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties were deduced from NOESY correlations. In the cytotoxic assay, the 5-(2-methylpropyldiene)-1H-pyrrol-2(5H)-one analogue (myceliothermophin E) exhibited inhibition against four cancer cell lines. In addition, the significant inhibitory effect of myceliothermophins A and C and the inactivity of myceliothermophins B and D revealed the importance of the relative configurations of 5-alkyl-5-hydroxyl (or 5-methoxyl)-1H-pyrrol-2(5H)-one moieties on their cytotoxicity potency against cancer cells.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Cytotoxic Polyketides Containing Tetramic Acid Moieties Isolated from the Fungus Myceliophthora Thermophila: Elucidation of the Relationship between Cytotoxicity and Stereoconfiguration

Yang

Chen

et al. 2007

Chemistry A European J

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“…It surprising that the structural similarity of NG-391 and NG-393 to the fusarins did not immediately trigger studies of their genotoxicity. Our confirmation that their mutagenicity rivals that of fusarin C and its 8Z isomer (18) raises the question of whether these compounds will be worth pursuing for biomedical applications (16,29). Additional research will be conducted to determine more accurately the mutagenic potency of 1 and 2 and, also, to determine the spectrum of mutations induced by these two compounds.…”

Section: Resultsmentioning

confidence: 92%

Production of Mutagenic Metabolites by Metarhizium anisopliae

Krasnoff

Sommers

Moon

et al. 2006

J. Agric. Food Chem.

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NG-391 (1) and NG-393 (2), previously reported from undescribed Fusarium species as nerve-cell growth stimulants, were identified from fermentation extracts of the entomopathogenic fungus Metarhizium anisopliae. These compounds are 7-desmethyl analogues of fusarin C and (8Z)-fusarin C, mutagenic toxins from Fusarium species that contaminate corn. A mutant strain of M. anisopliae (KOB1-3) overproduces 1 and 2 by ca. 10-fold relative to the wild-type strain, ARSEF 2575, from which it was derived. Overproduction of these compounds in KOB1-3 imparts a yellow pigmentation to the culture medium of the fungus. These compounds were inactive at 100 mug/disk in antimicrobial disk diffusion assays. Compound 1 was inactive at 100 ppm in a mosquitocidal assay. However, like their fusarin analogues, 1 and 2 exhibited potent S9-dependent mutagenic activity in the Salmonella mutagenicity test. Discovery of these highly mutagenic mycotoxins in M. anisopliae suggests that screening for production of NG-391 and NG-393 in strains that are used as biocontrol agents would be a prudent course of action. The impact of these findings on the use of M. anisopliae as a biocontrol agent is currently unknown and requires further investigation.

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“…Moreover, epoxypyrrolidines are important intermediates in organic synthesis. [14] Enal 3 a was engaged in an epoxidation reaction under basic conditions (H 2 O 2 , NaOH) to afford the polysubstituted pyrrolidines 9 and 10 as a separable mixture of diastereoisomers (d.r. 3:1).…”

Section: Resultsmentioning

confidence: 99%

Enantioselective Organocatalytic One‐Pot Amination/aza‐Michael/Aldol Condensation Reaction Sequence: Synthesis of 3‐Pyrrolines with a Quaternary Stereocenter

Desmarchelier

Coeffard

Moreau

et al. 2012

Chemistry A European J

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Primary amine-catalyzed direct conversion of α,α-disubstituted aldehydes into 3-pyrrolines with a quaternary stereocenter is reported. The one-pot enantioselective sequence is based on a α-amination, an aza-Michael addition of hydrazine, an aldol condensation dehydratation and proceeds with good yields and excellent levels of enantioselectivity. Synthetically attractive applications including the formation of aziridinopyrrolidine or epoxypyrrolidine derivatives with good yields and selectivities are also described.

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Determination by Asymmetric Total Synthesis of the Absolute Configuration of Lucilactaene, a Cell‐Cycle Inhibitor in p53‐Transfected Cancer Cells

Cited by 12 publications

References 28 publications

Cytotoxic Polyketides Containing Tetramic Acid Moieties Isolated from the Fungus Myceliophthora Thermophila: Elucidation of the Relationship between Cytotoxicity and Stereoconfiguration

Cytotoxic Polyketides Containing Tetramic Acid Moieties Isolated from the Fungus Myceliophthora Thermophila: Elucidation of the Relationship between Cytotoxicity and Stereoconfiguration

Production of Mutagenic Metabolites by Metarhizium anisopliae

Enantioselective Organocatalytic One‐Pot Amination/aza‐Michael/Aldol Condensation Reaction Sequence: Synthesis of 3‐Pyrrolines with a Quaternary Stereocenter

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