- Marliolide inhibits skin carcinogenesis by activating NRF2/ARE to induce heme oxygenase-1
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Heme oxygenase-1 (HO-1) catalyzes the enzymatic degradation of heme to produce three anti-oxidant molecules: carbon monoxide (CO), ferrous ion (Fe2+), and biliverdin. Induction of HO-1 is currently considered as a feasible strategy to treat oxidative stress-related diseases. In the present study, we identified marliolide as a novel inducer of HO-1 in human normal keratinocyte HaCaT cells. Mechanism-based studies demonstrated that the induction of HO-1 by marliolide occurred through activation of NRF2/ARE via direct binding of marliolide to KEAP1. Structure-activity relationship revealed chemical moieties of marliolide critical for induction of HO-1, which renders a support for Michael reaction as a potential mechanism of action. Finally, we observed that marliolide significantly inhibited the papilloma formation in DMBA/TPA–induced mouse skin carcinogenesis model and this event was closely associated with lowering the formation of 8-OH-G and 4-HNE in vivo. Together, our study provides the first evidence that marliolide might be effective against oxidative stress-related skin disorders.
- Lee, June,Mailar, Karabasappa,Yoo, Ok-Kyung,Choi, Won Jun,Keum, Young-Sam
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- Stereopure 1,3-butadiene-2-carboxylates and their conversion into non-racemic α-alkylidenebutyrolactone natural products by asymmetric dihydroxylation
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Dienoic esters 1 with the four possible permutations of the C=C configurations were prepared in two steps via non-stereoselective aldol additions followed by stereospecific β-eliminations. Sharpless dihydroxylations of these esters yielded natural and unnatural α-alkylidene-β-hydroxybutyrolactones 2. Among these were synthetic dihydromahubanolide B (cis,Z-2a), isodihydromahubanolide B (cis,E-2a) and, for the first time, litsenolide D1 (ent-trans,Z-2b) and the enantiomer trans,E-2b of litsenolide D2. Competitively, dihydroxyesters 10 were formed.
- Harcken, Christian,Brückner, Reinhard
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p. 3967 - 3971
(2007/10/03)
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- Efficient total synthesis of (-)-epilitsenolide C2 and (-)-isodihydro-mahubanolide B via a modified tungsten-mediated cycloalkenylation reaction
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An efficient method is developed for total synthesis of (-)-epilitsenolide C2 and (-)-isodihydro-mahubanolide B based on a modified cycloalkenylation of chiral alkynyltungsten compounds.
- Chen,Lo,Liu
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p. 1205 - 1207
(2007/10/03)
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- (Z)-3-alkylidene-4,5-dihydro-4-hydroxy-5-methyl-2-(3H)-furanones by regio- and diastereoselective ene reaction of singlet oxygen (Schenk reaction) with γ-hydroxy vinylstannanes: An enantioselective synthesis of dihydromahubanolide B
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(Z)-3-Alkylidene-4,5-dihydro-4-hydroxy-5-methyl-2-(3H)-furanones 5 were prepared from appropriately substituted propargylic alcohols 1 by a sequence of hydromagnesation to γ-hydroxy vinylstannanes 2, subsequent photooxygenation and reduction to stannyl diols 3, iododestannylation to iodo diols 4, and finally cyclization by palladium-catalyzed carbonylation (for 5a) or Ni(CO)2(PPh3)2 (for 5b,c). The reaction sequence can be performed enantioselectively by starting with chiral propargylic alcohols. The current approach constitutes a convenient four-step synthesis of optically active lactones 5 from readily available starting materials and is applied herein to the preparation of the natural lactone dihydromahubanolide B.
- Adam,Klug
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p. 567 - 572
(2007/10/02)
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- THE SYNTHESIS OF THE DIHYDROMAHUBANOLIDES
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Two epimeric, naturally occuring α-alkylidene-γ-butyrolactones have been prepared from a carbohydrate precursor, using a Wittig reaction to form an exocyclic double bond either with or without epimerisation at the centre α to the olefin, depending on the
- Wood, William W.,Watson, Graham M.
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p. 3201 - 3203
(2007/10/02)
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- The Total Synthesis of Lauraceae Lactones: Obtusilactones, Litsenolides, and Mahubanolides
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The total synthesis of obtusilactones (1a,b, 2a,b), mahubanolides (1c, 2c), epilitsenolides (5b, 6b), and dihydromahubanolides (4c, 5c, 6c) is described.The enolates derived from the α-phenylselenenyl esters (17a-c) were used as acrylate α-anion synthons; aldol addition to propargylaldehyde, followed by oxidation to the selenoxide and elimination, furnished the isomeric acetylenic esters 20a-c and 21a-c.In a similar manner, aldol addition to acrolein followed by oxidation/elimination yielded olefinic esters 18b,c and 19b,c.The acetylenic esters were saponified, and the corresponding carboxylic acids were converted by either mercuric ion-catalyzed or bicarbonate-catalyzed lactonization to the obtusilactones (1a,b, 2a,b) and mahubanolides (1c, 2c).The olefinic esters were saponified, and the corresponding carboxylic acids lactonized to γ-substituted lactones (30b,c, 32b,c 32c) by treatment with either phenylselenenyl chloride or iodine.The epilitsenolides (5b, 6b) and dihydromahubanolides (5c, 6c) were then obtained by treating the substituted γ-lactones with tri-n-butyltin hydride.Homogeneous catalytic hydrogenation (Rh(PPh3)3Cl) of isomahubanolide (2c) gave a mixture of dihydromahubanolides 4c and 6c.
- Rollinson, Susan Wells,Amos, Richard A.,Katzenellenbogen, John A.
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p. 4114 - 4125
(2007/10/02)
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- SYNTHESIS OF (-)-DIHYDROMAHUBANOLIDE B AND (-)-ISODIHYDROMAHUBANOLIDE B
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The total synthesis of (-)-dihydromahubanolide B and (-)-isodihydromahubanolide B isolated from the Amazonian Lauraceae Licaria mahuba (Samp.) Kosterm was achieved starting from (-)-methyl 5-hydroxymethyl-2,2-dimethyl-1,3-dioxolane-4-carboxylate which was readily available from L-(+)-tartaric acid.
- Tanaka, Akira,Yamashita, Kyohei
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p. 319 - 322
(2007/10/02)
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- ω-ETHYL, ω-ETHENYL AND ω-ETHYNYL-α-ALKYLIDENE-γ-LACTONES FROM CLINOSTEMON MAHUBA
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Key Word Index - Clinostemon mahuba; Lauraceae; mahuba lactones; α-alkylidene-β-hydroxy-γ-methylene-γ-lactones; α-alkylidene-β-hydroxy-γ-methyl-γ-lactones. The trunk wood of Clinostemon mahuba contains eight (3R)-2-alkylidene-3-hydroxy-4-methylenebutanolides, seven (3R,4S)-2-alkylidene-3-hydroxy-4-methylbutanolides and seven (3S,4S)-2-alkylidene-3-hydroxy-4-methylbutanolides distinguished by the alkylidene side chains with respect to their E- or Z-geometry, ethenyl, ethynyl or ethyl terminals and lengths (C16 or C18).
- Martinez V., Juan C.,Yoshida, Massayoshi,Gottlieb, Otto R.
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p. 459 - 464
(2007/10/02)
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