A Practical Synthesis of (−)-Oseltamivir†
Nobuhiro Satoh
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorTakahiro Akiba
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorSatoshi Yokoshima Dr.
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorTohru Fukuyama Prof.
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorNobuhiro Satoh
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorTakahiro Akiba
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorSatoshi Yokoshima Dr.
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorTohru Fukuyama Prof.
Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan, Fax: (+81) 3-5802-8694
Search for more papers by this authorThis research was supported financially in part by a grant for the 21st Century COE Program and a Grant-in-Aid (15109001 and 16073205) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. We are indebted to Dr. Kunisuke Izawa of Ajinomoto Co. for an ample supply of D-phenylalanine.
Graphical Abstract
So einfach wie möglich: Das immer noch stark nachgefragte Grippemedikament (−)-Oseltamivir-Phosphat (Tamiflu; siehe Schema) wurde ausgehend von Pyridin mithilfe billiger Reagentien synthetisiert, wobei die Zahl an Reinigungsschritten konsequent gering gehalten wurde. Die Syntheseroute umfasst eine asymmetrische Diels-Alder-Reaktion, eine Bromlactonisierung, eine Hofmann-Umlagerung und eine Dominoreaktion eines Bicyclo[2.2.2]-Systems in ein Aziridinintermediat.
Supporting Information
Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2007/z701754_s.pdf or from the author.
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