- Dehydrohispanolone Derivatives Attenuate the Inflammatory Response through the Modulation of Inflammasome Activation
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The NLRP3 inflammasome plays a critical role in inflammation-mediated human diseases and represents a promising drug target for novel anti-inflammatory therapies. Hispanolone is a labdane diterpenoid isolated from the aerial parts of Ballota species. This diterpenoid and some derivatives have demonstrated anti-inflammatory effects in classical inflammatory pathways. In the present study, a series of dehydrohispanolone derivatives (1-19) was synthesized, and their anti-inflammatory activities toward NLRP3 inflammasome activation were evaluated. The structures of the dehydrohispanolone analogues produced were elucidated by NMR spectroscopy and mass spectrometry. Four derivatives significantly inhibited IL-1β secretion, with 15 and 18 being the most active (IC50 = 18.7 and 13.8 μM, respectively). Analysis of IL-1β and caspase-1 expression revealed that the new diterpenoids 15 and 18 are selective inhibitors of the NLRP3 inflammasome, reinforcing the previously demonstrated anti-inflammatory properties of hispanolone derivatives.
- González-Cofrade, Laura,Oramas-Royo, Sandra,Cuadrado, Irene,Amesty, ángel,Hortelano, Sonsoles,Estevez-Braun, Ana,De Las Heras, Beatriz
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- Transformations of hispanolone. Novel Michael adducts with in planta activity against rice blast
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Two novel Michael adducts 9α-cyano-15,16-epoxy-7β-hydroxylabda- 13(16),14-dien-6-one (2) and 9α-cyano-15,16-epoxy-7-hydroxylabda-7,13(16), 14-trien-6-one (3) and the reduction product of 2, 9α-cyano-15,16-epoxy- 6β,7β-dihydroxylabda-13(16),14-diene (4), w
- Van Wyk, Albert W.W.,Gray, Christopher A.,Keyzers, Robert A.,Rivett, Douglas E.A.,Caira, Mino R.,Nader, Bassam S.,Davis, George E.,Werk, Todd L.,Davies-Coleman, Michael T.
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p. 8493 - 8498
(2007/10/03)
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- The absolute stereochemistry of a diterpene from Ballota aucheri
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The semi-synthetic transformation of hispanolone, isolated from Ballota africana, into βp-hydroxy-15,16-epoxylabda-8,13(16),14-trien-7-one has established an ent-labdane absolute stereochemistry for a diterpene metabolite originally isolated from B. aucheri.
- Gray, Christopher A.,Rivett, Douglas E.A.,Davies-Coleman, Michael T.
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p. 409 - 413
(2007/10/03)
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- A new route to 2,7- and 7-functionalized labdanes
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A new route for the synthesis of 2,7- and 7-functionalized labdanes starts from (R)-carvone (1). 11-Nordrim-7-en-9-one (15) is an appropriate starting material for the total synthesis of hispanone (21), a biologically active furolabdane isolated from the
- Hersel, Ulrich,Steck, Melanie,Seifert, Karlheinz
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p. 1609 - 1615
(2007/10/03)
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- Total synthesis of (-)-hispanolone and an improved approach towards prehispanolone
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On the basis of the recently reported construction of (±)-hispanolone (2), the enantiomerically pure form of (-),2, employed in our partial synthesis of the specific platelet activating factor receptor antagonist prehispanolone (3), was prepared from (S)-
- Cheung, Wing Shun,Wong, Henry N. C.
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p. 11001 - 11016
(2007/10/03)
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- Total syntheses of naturally occurring molecules possessing 1,7- dioxaspiro[4.4]nonane skeletons
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The syntheses of several naturally occurring molecules, namely prehispanolone, sphydrofuran, secosyrins, and syringolides are reviewed. Interestingly, these compounds are all structurally related, possessing a 1,7-dioxaspiro[4.4]nonane framework. The pivotal step in these synthetic endeavors involves the peracid oxidation of substituted 2- trimethylsilylfurans to but-2-en-4-olides. A subsequent intramolecular Michael addition procedure was also essential in the construction of the spiro skeleton. Two significant issues concerning regioselectivity and stereoselectivity are also addressed.
- Wong, Henry N. C.
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p. 1757 - 1765
(2007/10/03)
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