Total Synthesis of Entecavir
The Journal of Organic Chemistry2013Vol. 78(11), pp. 5482–5491
Citations Over TimeTop 18% of 2013 papers
Javier Velasco, Xavier Ariza, Laura Badía, Martí Bartra, Ramon Berenguer, Jaume Farràs, Joan Gallardo, Jordi García, Yolanda Gasanz
Abstract
Entecavir (BMS-200475) was synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (i) a stereoselective boron-aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (ii) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (iii) the coupling with a purine derivative by a Mitsunobu reaction.