Synthesis, Table of Contents Synthesis 2013; 45(3): 389-395DOI: 10.1055/s-0032-1317948 paper © Georg Thieme Verlag Stuttgart · New YorkFormal Synthesis of (–)-Oseltamivir Phosphate Authors Author Affiliations Milos Trajkovic Faculty of Chemistry, University of Belgrade, Studentski trg 16, POB 51, 11158 Belgrade 118, Serbia Fax: +381(11)3282537 Email: rsaicic@chem.bg.ac.rs Zorana Ferjancic* Faculty of Chemistry, University of Belgrade, Studentski trg 16, POB 51, 11158 Belgrade 118, Serbia Fax: +381(11)3282537 Email: rsaicic@chem.bg.ac.rs Radomir N. Saicic* Faculty of Chemistry, University of Belgrade, Studentski trg 16, POB 51, 11158 Belgrade 118, Serbia Fax: +381(11)3282537 Email: rsaicic@chem.bg.ac.rs Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Abstract The formal synthesis of (–)-oseltamivir phosphate (Tamiflu tm ) was accomplished starting from (S)-pyroglutamic acid. The synthesis comprised two carbon–carbon bond forming reactions, the first one being a diastereoselective, indium-mediated allylation of a pyroglutamic aldehyde derivative. However, attempts to effect the second carbon–carbon bond formation – cyclohexene ring closure – using an enol-exo aldolization of a dialdehyde resulted in the formation of a product with the opposite regioselectivity. This shortcoming could be overcome by using a reaction sequence of Mannich methylenation/ring-closing metathesis, which provided the desired regioisomer in high yield. Key words Key wordsantiviral agents - allylation - cyclization - metathesis - total synthesis Full Text References References 1a Kim CU, Lew W, Williams MA, Liu H, Zhang L, Swaminathan S, Bischofberger N, Chen MS, Mendel DB, Tai CY, Laver WG, Stevens RC. J. Am. Chem. Soc. 1997; 119: 681 1b Rohloff JC, Kent KM, Postish MJ, Becker MW, Chapman HH, Kelly DE, Lew W, Louie MS, McGee LR, Prisbe EJ, Schultze LM, Yu RH, Zhang L. J. Org. 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