PMID: 11916407Mar 28, 2002Paper

Total synthesis and initial structure-function analysis of the potent V-ATPase inhibitors salicylihalamide A and related compounds

Journal of the American Chemical Society
Yusheng WuJef K De Brabander

Abstract

Salicylihalamide A is the first member of a growing class of macrocyclic salicylate natural products that induce a variety of interesting phenotypes in cultured mammalian cells. Salicylihalamide A was reported to be a unique and highly differential cytotoxin and a potent inhibitor of the mammalian vacuolar (H(+))-ATPase. The total synthesis of both enantiomers of salicylihalamide A, a revision of the absolute configuration assigned to the natural product, and extensive structure-function studies with synthetic salicylihalamide variants are reported. These studies were possible only due to a highly efficient synthetic strategy that features (1) a remarkably E-selective ring-closing olefin metathesis to construct the 12-membered benzolactone skeleton 29, (2) a mild stereocontrolled elaboration to E-alkenyl isocyanate 41, and (3) addition of carbon, oxygen, and sulfur nucleophiles to isocyanate 41 to obtain salicylihalamide A and congeners. We demonstrate for the first time that salicylihalamide A is a potent inhibitor of fully purified reconstituted V-ATPase from bovine brain, and have identified several similarly potent side chain modified derivatives, including salicylihalamide dimers 43-45. In combination, these studies have l...Continue Reading

References

Oct 24, 2001·The Journal of Organic Chemistry·Karen L. EricksonMichael R. Boyd
Dec 1, 2000·Angewandte Chemie·Mahdi M Abu-OmarVirginie M Béreau

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Citations

Apr 27, 2007·Journal of the American Chemical Society·Xin JiangJef K De Brabander
Apr 21, 2011·The Journal of Organic Chemistry·Rambabu ChegondiPaul R Hanson
Jan 20, 2009·Organic Letters·Mikkel V DeBenedettoPaul E Floreancig
Sep 18, 2009·Cancer Treatment Reviews·Mario Pérez-SayánsAbel García-García
Oct 1, 2004·Chemistry : a European Journal·Christian HerbMartin E Maier
Mar 13, 2014·Antimicrobial Agents and Chemotherapy·Konstantin H MüllerClaude P Muller
May 13, 2006·Journal of Bioenergetics and Biomembranes·Emma Jean Bowman, Barry J Bowman
Apr 20, 2005·Chemistry : a European Journal·Sergei F Vyboishchikov, Walter Thiel
Jul 2, 2010·Chemical Society Reviews·Steven P Nolan, Hervé Clavier
Aug 16, 2005·Angewandte Chemie·Stefan BräseViktor Zimmermann
Apr 13, 2007·Nature·Angelique W WhitehurstMichael A White
May 9, 2006·American Journal of Physiology. Heart and Circulatory Physiology·J D RojasR Martínez-Zaguilán
Aug 29, 2003·The Journal of Biological Chemistry·Emma Jean BowmanMichael R Boyd
Sep 12, 2012·Organic & Biomolecular Chemistry·Dan BalanMark A Rizzacasa
Mar 5, 2004·The Journal of Biological Chemistry·Xiao-Song XieJef K De Brabander
Feb 3, 2005·Angewandte Chemie·Omid Soltani, Jef K De Brabander
Sep 14, 2011·Chemistry, an Asian Journal·Sandip A PujariKrishna P Kaliappan
Jun 1, 2016·ChemMedChem·Christopher M SchneiderGunda I Georg
Feb 27, 2018·Organic & Biomolecular Chemistry·Arun K GhoshMargherita Brindisi
Jan 2, 2009·Journal of Medicinal Chemistry·Yoshinori SugimotoTohru Oishi
Apr 1, 2009·The Journal of Organic Chemistry·Yoko YamakiAkira Otaka
Mar 15, 2003·The Journal of Organic Chemistry·Georgina A HollowayMark A Rizzacasa
Jun 6, 2003·Journal of the American Chemical Society·Xiang Wang, John A Porco
Aug 31, 2002·Organic Letters·Ruichao ShenJohn A Porco
Dec 15, 2005·Chemical Reviews·Kap-Sun Yeung, Ian Paterson
May 13, 2004·Chemical Reviews·Itaru Nakamura, Yoshinori Yamamoto
May 13, 2004·Chemical Reviews·Alexander Deiters, Stephen F Martin

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