- Asymmetric Nazarov Cyclizations of Unactivated Dienones by Hydrogen-Bond-Donor/Lewis Acid Co–Catalyzed, Enantioselective Proton-Transfer
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We report an enantioselective Nazarov cyclization catalyzed by chiral hydrogen-bond-donors in concert with silyl Lewis acids. The developed transformation provides access to tri-substituted cyclopentenones in high levels of enantioselectivity (up to 95% e.e.) from a variety of simple unactivated dienones. Kinetic and mechanistic studies are consistent with a reversible 4π-electrocyclization C?C bond-forming step followed by rate- and enantio-determining proton-transfer as the mode of catalysis. (Figure presented.).
- Metternich, Jan B.,Reiterer, Martin,Jacobsen, Eric N.
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supporting information
p. 4092 - 4097
(2020/09/01)
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- Development of alkyl glycerone phosphate synthase inhibitors: Structure-activity relationship and effects on ether lipids and epithelial-mesenchymal transition in cancer cells
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In aggressive tumors, alkylglyceronephosphate synthase (AGPS) controls cellular ether phospholipid utilization and metabolism to promote cancer cell proliferation and motility. SAR studies on the first-in-class AGPS inhibitor 1, discovered by our group, led to the 2,6-difluoro analog 2i which showed higher binding affinity than 1 in vitro. In 231MFP cancer cells, 2i reduced ether lipids levels and cell migration rate. When tested in PC-3 and MDA-MB-231 cancer cells, 2i specifically impaired epithelial to mesenchymal transition (EMT) by modulating E-cadherin, Snail and MMP2 expression levels. Moreover, the combination of siRNAs against AGPS and 2i provided no additive effect, confirming that the modulation of 2i on EMT specifically relies on AGPS inhibition. Finally, this compound also affected cancer cell proliferation especially in MDA-MB-231 cells expressing higher AGPS level, whereas it provided negligible effects on MeT5A, a non-tumorigenic cell line, thus showing cancer specificity.
- Stazi, Giulia,Battistelli, Cecilia,Piano, Valentina,Mazzone, Roberta,Marrocco, Biagina,Marchese, Sara,Louie, Sharon M.,Zwergel, Clemens,Antonini, Lorenzo,Patsilinakos, Alexandros,Ragno, Rino,Viviano, Monica,Sbardella, Gianluca,Ciogli, Alessia,Fabrizi, Giancarlo,Cirilli, Roberto,Strippoli, Raffaele,Marchetti, Alessandra,Tripodi, Marco,Nomura, Daniel K.,Mattevi, Andrea,Mai, Antonello,Valente, Sergio
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p. 722 - 735
(2019/01/04)
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- TRPA1 antagonists
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Compounds of formula (I) wherein R1, R2, R3, m, and Y are defined in the specification are TRPA1 antagonists. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds
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Page/Page column 24
(2015/09/22)
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- TRPA1 Antagonists
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Compounds of formula (I) wherein R1, R2, R3, m, and Y are defined in the specification are TRPA1 antagonists. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds an
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