The synthetic-technical development of oseltamivir phosphate tamiflu™:: A race against time

被引:54
作者
Abrecht, Stefan [1 ]
Federspiel, Muriel Cordon [1 ]
Estermann, Heinrich [1 ]
Fischer, Rolf [1 ]
Karpf, Martin [1 ]
Mair, Hans-Juergen [1 ]
Oberhauser, Thomas [1 ]
Rimmler, Goesta [1 ]
Trussardi, Rene [1 ]
Zutter, Ulrich [1 ]
机构
[1] F Hoffmann La Roche & Co Ltd, Div Pharmaceut, CH-4070 Basel, Switzerland
关键词
analytics; influenza neuraminidase inhibitor; oseltamivir phosphate; production; synthesis; technical development; NEURAMINIDASE INHIBITOR; SHIKIMIC ACID; BIOSYNTHESIS;
D O I
10.2533/chimia.2007.93
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The clinical development of the first orally available neuraminidase inhibitor prodrug oseltamivir phosphate (Tamiflu (TM)) proceeded very fast. In order to support this program an unprecedented team effort in chemical process research, development, piloting, production and analytics took place, which allowed the successful launch of Tamiflu (TM) in 1999, only two and a half years after it was licensed from Gilead Sciences. This article describes selected aspects of the commercially used synthesis route and a brief summary of alternative syntheses devised by Roche chemists.
引用
收藏
页码:93 / 99
页数:7
相关论文
共 15 条
  • [1] The synthetic development of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu®):: A challenge for synthesis & process research
    Abrecht, S
    Harrington, P
    Iding, H
    Karpf, M
    Trussardi, R
    Wirz, B
    Zutter, U
    [J]. CHIMIA, 2004, 58 (09) : 621 - 629
  • [2] BISCHOFBERGER NW, 1995, Patent No. 9626933
  • [3] Phosphoenolpyruvate availability and the biosynthesis of shikimic acid
    Chandran, SS
    Yi, J
    Draths, KM
    von Daeniken, R
    Weber, W
    Frost, JW
    [J]. BIOTECHNOLOGY PROGRESS, 2003, 19 (03) : 808 - 814
  • [4] Tamiflu: The supply problem
    Farina, Vittorio
    Brown, Jack D.
    [J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2006, 45 (44) : 7330 - 7334
  • [5] Industrial synthesis of the key precursor in the synthesis of the anti-influenza drug oseltamivir phosphate (Ro 64-0796/002, GS-4104-02):: Ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate
    Federspiel, M
    Fischer, R
    Hennig, M
    Mair, HJ
    Oberhauser, T
    Rimmler, G
    Albiez, T
    Bruhin, J
    Estermann, H
    Gandert, C
    Göckel, V
    Götzö, S
    Hoffmann, U
    Huber, G
    Janatsch, G
    Lauper, S
    Röckel-Stäbler, O
    Trussardi, R
    Zwahlen, AG
    [J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 1999, 3 (04) : 266 - 274
  • [6] De novo synthesis of Tamiflu via a catalytic asymmetric ring-opening of meso-aziridines with TMSN3
    Fukuta, Yuhei
    Mita, Tsuyoshi
    Fukuda, Nobuhisa
    Kanai, Motomu
    Shibasaki, Masakatsu
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (19) : 6312 - 6313
  • [7] Research and development of a second-generation process for oseltmivir phosphate, prodrug for a neuraminidase inhibitor
    Harrington, PJ
    Brown, JD
    Foderaro, T
    Hughes, RC
    [J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2004, 8 (01) : 86 - 91
  • [8] New, azide-free transformation of epoxides into 1,2-diamino compounds: Synthesis of the anti-influenza neuraminidase inhibitor oseltamivir phosphate (Tamiflu)
    Karpf, M
    Trussardi, R
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (06) : 2044 - 2051
  • [9] Hydroaromatic equilibration during biosynthesis of shikimic acid
    Knop, DR
    Draths, KM
    Chandran, SS
    Barker, JL
    von Daeniken, R
    Weber, W
    Frost, JW
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2001, 123 (42) : 10173 - 10182
  • [10] MAIR HJ, 1999, 1112999A2 EP