- A concise synthesis of R-(-)-cicutoxin, a natural 17-carbon polyenyne
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A concise synthesis of the natural polyenyne R-(-)-cicutoxin (1) is described. After several trials, the successful synthesis commenced with three key fragments, R-(-)-1-hexyn-3-ol (8), 1,4-diiodo-1,3-butadiene (9), and THP-protected 4,6-heptadiyn-1-ol (6
- Gung, Benjamin W.,Omollo, Ann O.
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- Expeditious synthesis of polyacetylenic water hemlock toxins and their effects on the major GABAA receptor isoform
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Classical synthetic approaches to highly unsaturated polyene/yne natural products rely on iterative cross-coupling of linear fragments. Herein, we present an expeditious and unified approach to the unsaturated backbone of polyacetylenes via domino cuprate addition/4π-electrocyclic ring opening of a stereodefined cyclobutene intermediate. This sets the stage for a detailed biological assessment of the role of Virol A and Cicutoxin as inhibitors of GABA induced chloride currents, providing further insight into the interaction of these highly potent toxins towards the GABAA receptor, including the structure-activity relationship of the derivatives.
- Berger, Martin,Chen, Yong,Bampali, Konstantina,Ernst, Margot,Maulide, Nuno
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p. 2008 - 2011
(2018/03/01)
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- Sn/Li exchange reactions in 1,ω-distannylated conjugated trienes and tetraenes: An enabling step for polyene synthesis
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Successive treatments of (1E,3E,5E)- or (1E,3Z,5E)-1,6-bis(tributylstannyl) hexa-1,3,5-triene with nBuLi and butanal rendered polyenyl alcohols resulting from one Sn/Li exchange reaction and exhibiting complete retention of the configuration of all C=C bonds. Mono- or dimethylated all-E-configured 1,6-distannylated conjugated trienes as well as all-E-1,8-bis(tributylstannyl) octa-1,3,5,7-tetraene and dimethylated congeners thereof reacted similarly. The respective Sn/Li exchange reactions affected the substructure Bu 3Sn-CH=CH with a 93-94:7-6 preference over Bu3Sn-CMe=CH and with a 90:10 preference over Bu3Sn-CH=CMe. all-E-1-Lithio-6- (tributylstannyl)hexa-1,3,5-triene was incorporated into navenone B after Negishi coupling and into (-)-cicutoxin after acylation. NMR spectroscopy of our navenone B specimen revealed that certain resonances were misassigned previously. Molecular tinkertoy: all-E-1,6-(Tributylstannyl)hexa-1,3,5-triene, all-E-1,8-(tributylstannyl)octa-1,3,5,7-tetraene, and related bis(tributylstannylated) polyenes undergomono-Sn/Li exchange reactions. They set the stage for terminus-differentiating functionalizations, which provide inter alianavenone B and (-)-cicutoxin.
- Burghart, Jochen,Brueckner, Reinhard
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p. 150 - 165
(2011/03/18)
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