68224-83-9Relevant articles and documents
Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition
Wu, Zhenhua,Suppo, Jean-Simon,Tumova, Sarka,Strope, Jonathan,Bravo, Fernando,Moy, Melody,Weinstein, Ethan S.,Peer, Cody J.,Figg, William D.,Chain, William J.,Echavarren, Antonio M.,Beech, David J.,Beutler, John A.
, p. 1711 - 1716 (2020/10/19)
Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
Synthesis and Biological Evaluation of New (-)-Englerin Analogues
López-Suárez, Laura,Riesgo, Lorena,Bravo, Fernando,Ransom, Tanya T.,Beutler, John A.,Echavarren, Antonio M.
, p. 1003 - 1007 (2016/05/24)
We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).
α,β-Unsaturated Gold(I) Carbenes by Tandem Cyclization and 1,5-Alkoxy Migration of 1,6-Enynes: Mechanisms and Applications
Calleja, Pilar,Pablo, óscar,Ranieri, Beatrice,Gaydou, Morgane,Pitaval, Anthony,Moreno, María,Raducan, Mihai,Echavarren, Antonio M.
supporting information, p. 13613 - 13618 (2016/09/13)
1,6-Enynes bearing OR groups at the propargyl position generate α,β-unsaturated gold(I)-carbenes/ gold(I) stabilized allyl cations that can be trapped by alkenes to form cyclopropanes or 1,3-diketones to give products of α-alkylation. The best migrating group is p-nitrophenyl ether, which leads to the corresponding products without racemization. Thus, an improved formal synthesis of (+)-schisanwilsonene A has been accomplished. The different competitive reaction pathways have been delineated computationally.
