198481-99-1Relevant articles and documents
Total synthesis of (-)-salicylihalamide A.
Snider,Song
, p. 1817 - 1820 (2001)
[see structure]. A 16-step synthesis of the novel cytotoxin salicylihalamide A (1E) has been achieved in 3.3% overall yield using ring closing metathesis to generate the macrolide and addition of (1Z,3Z)-hexadienylcuprate (2), which was generated in situ from ethylcuprate and acetylene, to alkenyl isocyanate 3 to form the side chain.
Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide
Sugimoto, Yoshinori,Konoki, Keiichi,Murata, Michio,Matsushita, Masafumi,Kanazawa, Hiroshi,Oishi, Tohru
experimental part, p. 798 - 806 (2009/11/30)
Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase
Total synthesis and initial structure - Function analysis of the potent V-ATPase inhibitors salicylihalamide A and related compounds
Wu, Yusheng,Liao, Xibin,Wang, Ruifang,Xie, Xiao-Song,De Brabander, Jef K.
, p. 3245 - 3253 (2007/10/03)
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 laid the foundation for ongoing studies aimed at a comprehensive understanding of salicylihalamide's mode-of-action, of potential relevance to the development of lead compounds for the treatment of osteoporosis and cancer.
Enantioselective total synthesis of salicylihalamides A and B
Labrecque, Denis,Charron, Sylvie,Rej, Rabindra,Blais, Charles,Lamothe, Serge
, p. 2645 - 2648 (2007/10/03)
We have devised a total synthesis of (12R,13S,15R) salicylihalamides A and B, which allowed revision of the absolute stereochemistry of the natural compounds. The same strategy was then applied to the preparation of naturally occurring salicylihalamides.
