- An Enantioselective Iodolactonization/Cross-Coupling Protocol for the Synthesis of Highly Substituted Enol Lactones
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γ-Alkynoic acids readily undergo iodolactonization to give iodoenol lactones. Using commercially available (DHQD)2PHAL this transformation can be rendered asymmetric. In desymmetrization reactions of dialkynoic acids, good to very good enantioselectivities can be observed. Alternatively, kinetic resolution of already chiral, racemic γ-alkynoic acids can be carried out. The products of these iodolactonizations, iodoenol lactones, are suitable substrates for Palladium catalyzed cross-couplings. Negishi- as well as Sonogashira couplings can be carried out and allow the efficient synthesis of highly substituted enol lactones.
- Fricke, Christoph,Wilking, Michael,Daniliuc, Constantin G.,Hennecke, Ulrich
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p. 3158 - 3166
(2018/07/06)
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- Design, synthesis, and structure-activity relationships of haloenol lactones: Site-directed and isozyme-selective glutathione S-transferase inhibitors
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Overexpression of glutathione S-transferase (GST), particularly the GST-π isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-π inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-π, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-π inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-π was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-π with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.
- Wu, Zhixing,Minhas, Gurpreet Singh,Wen, Dingyi,Jiang, Hualiang,Chen, Kaixian,Zimniak, Piotr,Zheng, Jiang
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p. 3282 - 3294
(2007/10/03)
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- Insecticidal esters of substituted furan methanol
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Substituted acetate compounds represented by the formula STR1 which are useful as pesticides and pesticidal composition containing the substituted acetate compounds as active ingredients, as well as processes for preparing the compounds and the compositio
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