912291-95-3Relevant academic research and scientific papers
RCM macrocyclization made practical: An efficient synthesis of HCV protease inhibitor BILN 2061
Shu, Chutian,Zeng, Xingzhong,Hao, Ming-Hong,Wei, Xudong,Yee, Nathan K.,Busacca, Carl A.,Han, Zhengxu,Farina, Vittorio,Senanayake, Chris H.
supporting information; scheme or table, p. 1303 - 1306 (2009/04/06)
We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using 1H NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macro cyclic product over the diene substrate.
Efficient large-scale synthesis of BILN 2061, a potent HCV protease inhibitor, by a convergent approach based on ring-closing metathesis
Yee, Nathan K.,Farina, Vittorio,Houpis, Ioannis N.,Haddad, Nizar,Frutos, Rogelio P.,Gallou, Fabrice,Wang, Xiao-Jun,Wei, Xudong,Simpson, Robert D.,Feng, Xuwu,Fuchs, Victor,Xu, Yibo,Tan, Jonathan,Zhang, Li,Xu, Jinghua,Smith-Keenan, Lana L.,Vitous, Jana,Ridges, Michael D.,Spinelli, Earl M.,Johnson, Michael,Donsbach, Kai,Nicola, Thomas,Brenner, Michael,Winter, Eric,Kreye, Paul,Samstag, Wendelin
, p. 7133 - 7145 (2007/10/03)
A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metath
Epimerization reaction of a substituted vinylcyclopropane catalyzed by ruthenium carbenes: Mechanistic analysis
Zeng, Xingzhong,Wei, Xudong,Farina, Vittorio,Napolitano, Elio,Xu, Yibo,Zhang, Li,Haddad, Nizar,Yee, Nathan K.,Grinberg, Nelu,Shen, Sherry,Senanayake, Chris H.
, p. 8864 - 8875 (2007/10/03)
A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.
