320573-70-4Relevant academic research and scientific papers
Phosphate tether-mediated approach to the formal total synthesis of (-)-salicylihalamides A and B
Chegondi, Rambabu,Tan, Mary M. L.,Hanson, Paul R.
experimental part, p. 3909 - 3916 (2011/07/08)
A concise formal synthesis of the cytotoxic macrolides (-)- salicylihalamides A and B is reported. Key features of the synthetic strategy include a chemoselective hydroboration, highly regio- and diastereoselective methyl cuprate addition, Pd-catalyzed formate reduction, and an E-selective ring-closing metathesis to construct the 12-membered macrocycle subunit. Overall, two routes have been developed from a readily prepared bicyclic phosphate (4 steps), a 13-step route and a more efficient 9-step sequence relying on regioselective esterification of a key diol.
Stereoselective synthesis of the macrocyclic core of (-)-salicylihalamides A and B
Yadav,Sundar Ram Reddy
, p. 1070 - 1076 (2008/02/02)
Stereoselective synthesis of the macrocyclic core of salicylihalamides A and B is described. The synthetic strategy features stereoselective iodolactonization, Sharpless asymmetric epoxidation, Mitsunobu esterification, and ring-closing metathesis. Georg
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.
Total synthesis of (-)-salicylihalamide.
Fuerstner,Dierkes,Thiel,Blanda
, p. 5286 - 5298 (2007/10/03)
A concise total synthesis of the potent cytotoxic marine natural products salicylihalamide A and B (la, b) is reported. Key steps of our approach were the asymmetric hydrogenation reactions of beta-keto esters 18 and 32 catalyzed by [((S)-BINAP)Ru-Cl2]2. NEt3 and the cyclization of the macrolide core by ring closing olefin metathesis (RCM) using the "second-generation" ruthenium carbene complex 24 as the catalyst which bears an imidazol-2-ylidene ligand. The EIZ ratio obtained in this macrocyclization reaction was determined by the protecting groups at the remote phenolic OH group of the cyclization precursor. The elaboration of the resulting cycloalkene 37 into the final target involved a CrCl2-mediated synthesis of vinyliodide 49 which, after deprotection, did undergo a copper-catalyzed cross-coupling process with the (Z,Z)-configurated carboxamide 42 to form the labile enamide moiety of 1. Compound 42 was derived from a palladium-catalyzed Negishi coupling between butynylzinc chloride and 3-iodoacrylate 39 followed by a Lindlar reduction of enyne 40 thus obtained and a final aminolysis of the ester group.
